Download Upper respiratory tract infections

Basic principles of infectious
diseases
The term infectious diseases applies when an interaction with a microbe
causes damage to the host and the associated damage or altered physiology
results in clinical signs and symptoms of disease.
So pathogen is defined as any microrganism that has the capacity to cause
disease.
Not all pathogens have an equal probability of causing disease in the same host
population.
Virulence provides a measure of pathogenicity: for example encapsulated
pneumococci are more virulent than nonencapsulated pneumococci.
Escherichia coli strains expressing Shiga-like toxin are more virulent than those
that do not express these toxins
Opportunistic microrganisms
These microrganisms, usually do not cause disease in people with intact host
defence systems, on the contrary, they can cause devasting diseases in many
hospitalized and immunocompromized patients.
Most microrganisms with a capacity to multiply in humans (including members
of the indigenous commensal flora) cause disease more readily in individuals
with underlying chronic diseases or different compromises.
The term opportunist indicates well this category of pathogen.
Opportunistic pathogens a vary emergency in hospital are considered,
they are vehicolated by paramedical staff or assistance staff
Interaction of pathogenic
microrganisms with host
Adherence indicates the process by
which the microrganisms bind to
surfaces (initial interaction between
pathogenic microrganism and host).
It is the first step of cellular invasion
and toxins delivery process by
microbial pathogens.
Adhesins are microbial surface
molecules binding the organisms to
host surfaces.
Capsules are formed by extracellular
polymeric substances. They inhibits
phagocytosis.
Interaction of pathogenic microrganisms
with host: other factors
Fibrillae are the fine “hairy” structures on bacterial cells.
Fimbriae are nonflagellar filamentous structures on bacterial cells.
Glycocalyx is a superficial polysaccharide-containing structure on cellular
surface.
Lectins are glycoproteins that inhibit specific binding to carbohydrates.
Interaction of pathogenic
microrganisms with host: receptors
Receptors are host molecules able to recognize and bind
the microbial adhesins.
A single adhesin may have more than one receptor, and a single
receptor may be recognized by many different adhesins.
The central role of adhesins in microbial colonization and
pathogenesis makes them ideal target for preventive and
therapeutic treatment
Examples in which bacterial adherence
correlates with bacterial virulence
Infection
Organism
Comments
Cystitis
E. coli
Infection correlates with
adhesin type 1 fimbriae
Pyelonephritis
E. coli
Infection correlates with
adhesin P fimbriae
Urethritis
Strept. sanguis and
other bacteria
Otitis media
Streptococcus
pneumoniae
Infection correlates with
adhesins, fimbriae and
type II outer membrane
proteins.
Infection correlates with
adherence to pharyngeal
epitelial cells
Specific adherence mechanisms
and their roles in pathogenesis
Microbial biofilms
Many of the studies of bacterial adherence have been done on free-floating
“planktonic” bacteria growing in culture.
In nature, however many bacteria exist in a complex community-like structure
known as Biofilm.
Biofilms are bacterial populations that are inclosed in a matrix of extracellular
polymeric substances.
Microbial biofilms
Bacteria form microcolonies with conelike and mushroom-shaped morphologies by
adhering to each other and to a surface.
Water-filled channels surround the microcolonies and function somewhat like a primitive
circulatory system, allowing access to nutrients and interbacterial communication
Microbial Biofilms
In the medical area biofilms are seen in native valve endocarditis, otitis media, dental plaque
and they are a problem for cystic fibrosis patients.
Biofilms also form on synthetic medical implants, including, intravascular
catheters, artificial valves, pacemakers, orthopedic devices and contact lenses.
Medical device
Central venous catheter
Prosthetic heart valve,
urinary catheters
Artificial valve prosthetic
Intrauterine device
Biofilm-associated microrganisms
CN staphylococci, Staphyl aureus, Enteroc. faecalis,
Klebsiella pneum. Pseudomonas aeruginosa
Viridans streptococci, CN staphylococci, enterococci
S.aureus, E. coli, K. pneumoniae, Proteus mirabilis
Streptococcus ssp. Staphylococcus epidermidis
Staphylococcus aureus, epidermidis, enterococcus
ssp
Microbial Biofilms
One of the characteristics of Biofilms is their increased resistance to antibiotics.
Bacterial biofilms have been reported to be up to 500 times more resistant to antibiotics than
planktonic cells. There are several properties of biofilms that could contribute to increased
resistance to antibiotics. The esopolysaccharide matrix or slime that surrounds the cells may create
an exclusion barrier to antimicrobials or inactive them. Bacteria in biofilms grow more slowly and
slower growth may lead to decreased uptake of the drugs.
Biofilms formation
Biofilms are formed in two phases. The first phase is an initial reversible adherence
to a surface. Several factors contribute, including surface hydrophobicity, proteic adhesins and
capsular polysaccharides.
The second phase involves intracellular adhesion, which results in microcolonies formation and
complex biofilm architecture
Biofilms formation
Pili and flagella have been shown to be important in biofilms formations. Strains lacking flagella
appear unable to establish initial adherence to a substrate and microcolony formation.
Elucidation of molecular mechanisms of biofilms formation should identify new targets for
chemotherapy and provide new approaches to controlling biofilms formation.
Respiratory tract infections
Respiratory tract infections may be devided into: upper and lower tract
Upper respiratory tract infections
The common cold
Is the traditional term used to indicate a vary common syndrome of upper respiratory tract.
Common cold is the most common infectious disease in humans (each adult contracts two to
four infections a year, children may have six to ten cold a year).
The major respiratory viruses causing colds are found in the family of rhinovirus myxovirus,
paramyxovirus,adenovirus, piconavirus and coronavirus (the rhinovirus group accounts
for more than 50% of cases in adults). In total more than 200 different viral types cause colds.
Eyes congestion
A small number of colds is complicated by bacterial
infections of the paranasal sinuses and the
middle ear, and require antimicrobial therapy.
The common cold: incidence, signs
and symptoms
Respiratory infections have a seasonal incidence (in the colder mounths, in
temperate areas and in rainy seasons they, more frequently, occur).
Signs and symptoms
Symptoms are cough, sore throat, runny nose, nasal congestion accompanied
by headache, fatigue and loss appetite.
The common cold: treatment
Not many commercial remedies provide a good symptomatic relief.
The first-generation antihistamines and the nonsteroidal anti-inflammatory drugs (NSAID) are
commonly used.
Antihistamines are recommended in control of rinorrhea and nasal mucus.
NSAID are used in reducing cough, probably through blocking prostaglandin action, and in
control of headaches, malaise and other symptoms.
The combination of a first-generation antihistamines with NSAID provides a good relief in
common cold
The development of a new vaccine is difficult, because many different viruses are implicated
in common cold.
Pharyngitis
Acute pharyngitis is an inflammatory syndrome of the pharynx caused by both
viral and bacterial agents.
Most cases are of viral etiology and occur as part of common cold and influenzal
syndromes.
The most important bacterial infections are due to the group A β hemolytic
Streptococcus (Streptococcus pyogenes).
It is important to differentiate streptococcal from viral pharyngitis because only
bacterial forms are sensitive to penicillin.
Streptococcal pharyngitis may be complicated by acute rheumatic fever and
acute glomerulonephritis.
There are other uncommon or rare types of pharyngitis
and for some of these, specific treatment is available
Etiology: causes of pharyngitis
Etiology
Viral
Rhinovirus
coronavirus
Influenza virus
Epstein Barr virus
syndrome/disease
%
Common cold
Common cold
influenza
Infectious mononucleosis
20
>5
2
<1
Cytomegalovirus
Infectious mononucleosis
<1
Streptococcus pyogenes
Pharyngitis/tonsillitis
15-30
Mixed anaerobic bacteria
Haemophilus influenzae
Staphylococcus aureus
Corynebacterium
diphteriae
Vincent's angina
Pharyngitis
Pharyngitis
<1
<1
<1
Diphtheria
>1
pneumonia
<1
Bacterial
Mycoplasmal
Mycoplasma pneumoniae
Unknown
40
Pathogenesis
The pathogenetic mechanisms of pharyngitis are different in according
to various etiologic agents.
In viral infections caused by adenovirus and coxsackievirus, direct invasion of pharyngeal
mucosa occurs.
In infections caused by Streptococcus pyogenes, many factors influence colonization and
invasion in host tissue (natural and acquired host immunity, interference by other bacteria
present in the oropharynx, different M-types).
Streptococcus pyogenes elaborates a number of extracellular factors, including pyrogenic
exotoxins, hemolysins, streptokinase, deoxyribonuclease, proteinase, hyaluronidase.
Streptococcal pharyngitis
The severity of infections varies greatly.
In severe cases, there is marked pharyngeal pain, odinophagia and a temperature
of 39.4 °C.
Headache and abdominal pain may occur; the pharyngeal membrane is fiery red,
grayish-yellow exudate is presente on the tonsils.
Enlarged, cervical nodes and a rise in the number of leukocytes are typical
in acute suppurative bacterial infection
Streptococcal pharyngitis: complications
Complications of acute streptococcal pharyngitis, may include: acute reumathic fever, acute
glomerulonephritis and invasive infections (meningitis, endocarditis etc)
There is a general association of specific M serotypes with these complications
Scarlet fever
Infection with strains of Streptococcus pyogenes producing pyrogenic
exotoxins causes scarlet fever. The body is covered by a characteristic
erythematous rash followed by desquamation.
The tongue is red, and the papillae are enlarged (strawberry tongue)
Characteristics of rash:
is fine and blanches upon pressure
appareas 12-48 hours after the fever
generally it starts on the chest
Staphylococcal pharyngitis
Staphylococcus aureus causes pharyngitis
expecially in children (1% of cases)
Staphylococcal pharyngitis is
characterized by:
• Mucopurulent drainage
• Mucosal erythema
• Localized pustules
Vincent's angina (Henry Vincent)
Vincent's angina also called: acute necrotizing ulcerative gingivitis is a
mixed bacteria-spirochetal infection usually present in patients with poor
dental hygiene and in immunocompromized patients.
Inflamed and ulcered gingivae and halitosis may
characterize this form.
Exudative tonsillitis, pharyngeal pain and
dysphagia occurs. Septic emboli to the lung may
lead to pulmonary abscesses and empyema.
Treatment includes irrigation and removal of
necrotic areas, in untreated cases, infection can
spread to the bones.
Infectious mononucleosis
Pharyngitis often exudative occurs in many cases of infectious mononucleosis.
The mononucleosis syndrome is caused by EBV or cytomegalovirus.
Fever, fatigue, malaise, petechiae are present associated with headache.
Posterior and anterior cervical adenopathy is common and inguinal nodes are more
frequently enlarged.
Low-grade temperature and halitosis serves to differentiate this form from streptococcal
pharyngitis.
Diphtheria
Diphtheria still occurs in members of socio-economically disadvantaged populations.
Human infection is caused by Corynebacterium diphtheriae. It colonizes
pharyngeal tract forming a characteristic tonsillar or nasopharyngeal pseudomembrane
adherent to the tonsils and pharyngeal mucosa, causing bleeding and occlusion.
Swollen neck is present. Patients may experience tiredness, pallor and fast heart rate.
These symptoms are caused by the toxin released by bacterium.
The major damages include cardiac function with
myocarditis and peripheral neutropathy.
The less severe forms are restricted to the skin
(caracteristic lesions).
Patients are treated with repeated course of antitoxin.
Antibiotics are used in patients or in asymptomatic
carriers to eradicate Corynebacterium diphtheriae,
to reduce the numbers of bacteria and to prevent
their trasmission.
Diagnosis
The first objectives in diagnosis of acute pharyngitis are to distinguish cases of common
viral etiology, which predominate, and do not require antimicrobial therapy, from those
due to S. pyogenes or other unusual organisms for which treatment is available.
This distinction is critical because many patients continue to receive unnecessary
antimicrobials increasing prescription for expensive broad-spectrum agents.
The presence of pharyngeal or tonsillar exudates, adenophaty or skin rash helps in
differential diagnosis, but these findings are not specific in most cases
Several commercial kits are available for rapid detention of
group A streptococcal antigen from throat swabs. Rapid tests
are 60-90% sensitive and 98-99%specific when compared
to colture methods.
The patient's history and epidemiologic factors may help in
suggesting a specific etiologic diagnosis in cases in which
cultures or rapid antigen tests are negative for group A streptococci
Treatment
Patients with Streptococcal pharyngitis should receive a 10-day dose of penicillin
(or equivalent antibiotic). In allergic patients to penicillin erythromycin is recommended.
Antibiotic treatment serve to prevent suppurative complications (peritonsillar abscess,
sinusitis, otitis and pneumonia).
Vincent's angina: responds to an oral penicillin such as amoxicillin plus metronidazole
or amoxicillin-clavulanate. Peritonsillar abscesses can be treated by surgical drainage
or incision
Diphtheria: the treatment requires both antimicrobials and hyperimmune diphtheria
antitoxin
Viral pharyngitis: amantidine or rimantidine can reduce symptoms in uncomplicated
influenza, also neuroaminidase inhibitors have a similar effect.
Acyclovir, valacyclovir and foscarnet are available for the treatment of ulcerative
oropharyngeal Herpes simplex virus infection in immunocompromized patients
Otitis
Otitis may be defined such as an inflammatory condition of the ear characterized
by pain, fever, abnormalities of hearing and vertigo.
Is devided into: externa and media otitis
Ear anatomy
Otitis externa
Otitis externa: regards the outer ear (auricle pavilion and auditory canal).
The esternal auditory canal is long 2.5 cm. The microbial flora is similar to flora
of the skin (Staphylococcus epidermidis, S. aureus, Corynebacteria
and anaerobic bacteria)
Infections of the external canal may be subdivided into four categories:
Acute localized otitis externa
Acute diffuse otitis externa
Chronic otitis
Invasive otitis externa
Acute localized otitis externa
Acute localized otitis externa may occurs as a foruncle due to S. aureus
Pain is severe
Bluish, red hemorrhagic fluid may be frequent on auditory canal or on tympanic
membrane, adenopathy is often present.
Local treatment or systemic antibiotic treatment are curative
Incision or drainage are necessary in case of severe pain
Acute diffuse otitis externa
Acute diffuse otitis externa (swimmer's ear) occurs in hot, humid
wheathers
The skin is edematous and red. Gram negative bacilli especially
Pseudomonas aeruginosa play an important role in etiology.
Irrigation with hypertonic saline solution (3%), or cleansing with mixtures
of alcohol and acetic acid may be used initially.
A 10-day regiment of a fluorochinolone otic solution or ear drops
associated with hydrocortisone serve to reduce local inflammation and
to block infection.
Chronic otitis externa
The most frequent cause of chronic otitis externa is chronic suppurative otitis media
with perforated tympanic membrane.
Rare causes include: tubercolosis, syphilis and sarcoidosis.
Invasive otitis externa
Is a severe necrotizing infection that spreads from the ear canal to adjacent areas of
soft tissue, cartilage and bone.
Frank pain and inflammation are accompanied by the drainage of pus from the canal.
Diabetic, immunocompromized and debilitated patients are at particular risk.
Pseudomonas aeruginosa is almost always the etiologic agent.
Systemic therapy including anti-Pseudomonas drug should be used.
Association of ceftazidime, cefepime or piperacillin with an aminoglycoside (gentamicin
or tobramycin) should be considered.
Otitis media
Otitis media is defined by the presence of fluid in the middle ear accompanied by signs or
symptoms
Otitis media: epidemiology
Otitis media is a pediatric disease. The peak incidence occurs in the first 3 years of life.
The highest incidence of acute otitis media occurs between 6 and 24 months of age
The disease is less common in adolescens and adults
Children with acquired immunodeficiency syndrome have a higher incidence of otitis
media beginning at 6 months of age
Otitis media is infrequent in adults, but the bacteriology and therapy is similar to those in
children
Otitis media: pathogenesis
The middle ear includes: the nares, nasopharynx and eustachian tube.
Anatomic or functional disfunction of the eustachian tube appears to play an important role
in the development of otitis media.
Eustachian tube has three physiologic functions:
Protection from nasopharyngeal secretions
 Drainage of secretions into the nasopharynx
• Ventilation of the middle ear to equilibrate air pressure

When one or more of these functions are compromised, the result is the development
of fluid and infection in the middle ear. Congestion of the mucosa of the eustachian tube may
result in obstruction, and if bacterial pathogens are present a suppurative otitis can occur
Etiology of otitis media
Bacteria
Streptococcus pneumoniae and Haemophilus influenzae are the most frequent
cause in all age groups
Streptococcus pneumoniae is the most important bacterial cause of otitis media
(a 7 valent conjugate polysaccharide vaccine serve to
prevent this disease)
Haemophilus influenzae is a significant cause of otitis media in older children,
adolescent and adults
Moraxella catarrhalis was isolated from 10% of children with acute otitis media.
Before 1970, all strains of M. catarrhalis were sensitive to penicillin
Today most strains produce β-lactamase and are resistant to
penicillin ampicillin and amoxicillin
Etiology of otitis media
Bacterial Pathogen
Mean
Range
Strep. pneumoniae
38
27-52
Haemoph.
influenzae
27
16-52
Moraxella
catarrhalis
10
2-15
Streptoc. pyogenes
3
0-11
Staphylococ.
aureus
2
0-16
Miscellaneous
8
0-24
Viruses
28
12-35
Bacterial pathogens isolated from middle ear fluid in children with acute otitis media.
Total percentages are greater than 100% because of multiple pathogens may be isolated
Etiology of otitis media
Viruses
Many studies identify respiratory viruses or viral antigens in 25% of middle ear fluids of
children with acute otitis media.
The most important viruses found in middle ear fluids are:
Respiratory syncytial viruses
Influenza virus
Enteroviruses
Rhinoviruses
Chlamydia and unusual organisms
Chlamydia trachomatis is associated with acute respiratory infections in infants
younger than 6 mounths, and is a cause of acute infections of the middle ear in this age group
Uncommon forms of otitis include:
Diphtheritic otitis (bilateral form of otitis media with effusion due to diphtheria bacillus)
Tuberculous otitis (accounts for only 0.04% of all cases of chronic suppurative otitis media).
Otogenous tetanus (secondary to chronic ear infections)
Otitis due to Mycobacterium chelonae (chronic otorrhea and tympanic membrane perforation)
Diagnosis and clinical course
Acute otitis media is defined by the presence of fluid in the middle ear accompanied by
symptoms and acute illness.
Specific symptoms
Nonspecific symptoms
Ear pain
Ear drainage
Fever
Lethargy
Irritability
Signs and symptoms usually resolve with antimicrobial treatment
Antimicrobial treatment
There are now 19 antimicrobial agents approved by the Food and Drug Administration for
treatment of acute otitis media.
Amoxicillin remains the drug of choice for initial treatment.
The drug is ineffective against -lactamase-producing strains of Haemophilus influenzae and
Moraxella catarrhalis (H. influenzae and M. catarrhalis are responsible for about 30% and
10% of acute otitis media cases respectively)
For patients with known and severe allergy to β-lactam antibiotics, a macrolide (erithromycin,
azithromycin,or clarithromycin) is preferred.
Decongestants, and corticosteroids administered alone or in combination with an
antihistamine are used extensively for the treatment of otitis media with effusion.
Sinusitis
• Sinusitis is an inflammatory condition
of one or more of the paranasal
sinuses (frontal, sphenoid, ethmoid,
• mascellar sinus)
• Most acute cases result from infection,
other causes include allergy.
• Acute infectious sinusitis can be
classified into various categories on
the basis of different characteristics
including the immune status of patient
or its viral, bacterial or fungal etiology.
• The knowledge of these categories is
important to understand the
pathogenesis and to optimize the
treatment of this disease.
Paranasal sinuses anatomy
Sinusitis: classification
Sinusitis can be classified on the basis of symptoms persistence into
acute (symptoms persisting less than four weeks)
subacute (4-8 weeks)
chronic (8 weeks or more)
All three types of sinusitis have similar symptoms and are often difficult to
distinguish.
Sphenoid (not visible)
Acute sinusitis
Acute sinusitis is often caused by an upper respiratory tract infection generally
of viral origin.
In case of bacterial infection, three are the most common etiological agents:
Streptococcus pneumoniae
Haemophilus influenzae
Moraxella catarrhalis
Until recently Haemophilus influenzae was the most common bacterial agent.
However introduction of the H. influenzae type B vaccine has decreased the
number of cases.
Acute sinusitis: other causes
Other sinusitis causing bacterial pathogens include:
Staphylococcus aureus and other streptococci species
Anaerobic bacteria
Less common Gram negative bacteria
Viral sinusitis typically lasts for 7 to 10 days, bacterial sinusitis is more
persistent.
Acute episodes can also result from fungal invasion. These infection are
typically seen in patients with diabetes or other immune deficiencies syndromes
Subacute sinusitis
Subacute sinusitis: infection is present for more than
four but less than eight weeks. Symptoms may be less
severe and include nasal congestion or post-nasal
drip.
Chronic sinusitis
Chronic sinusitis, by definition, lasts more than three months and can be caused by different
diseases. Symptoms may include any combination of nasal congestion, facial pain, headache,
night-time coughing, general malaise etc.
Often chronic sinusitis can reduce sense of smell.
In a small number of cases chronic sinusitis
is associated with a dental infection
Chronic sinusitis: complicated cases
Chronic sinusitis cases are subdivided into cases with polyps and cases without polyps.
When polyps are present (ethmoid or mascellary sinuses), the condition is more severe.
Abnormally narrow sinus and deviated septum blocks the drainage from the sinus cavities
contribuiting to infections.
A combination of anaerobic and aerobic bacteria including Staphylococcus aureus and
coagulase-negative staphylococci can occur. Also fungi play an important role in this disease
(fungi can be found in the nasal cavities and sinuses of most patients with sinusitis).
Antibiotic treatment provide a reduction of inflammation.
Treatment of sinusitis
Nasal irrigation may help in cases of chronic sinusitis, decongestant sprays may
provide relief.
Antibiotic treatment
Most cases of sinusitis are caused by viruses and resolve without antibiotics.
If symptoms do not resolve within 7 days, amoxicillin/clavulanate (Augmentin)
is used.
Fluoroquinolones and macrolide antibiotics are indicated in patients
allergic to penicillins.
Corticosteroids
Intranasal corticosteroids are used in combination with antibiotics.
Lower tract respiratory infections
Bronchitis
Bronchitis is an inflammatory syndrome of the tracheobronchial tree. It occurs most often
during the winter months, when respiratory tract infections are prevalent.
May be divided in acute and chronic.
Acute bronchitis: clinical finding and
etiology
 Cough occurs in approximately 50% of cases of acute bronchitis.
 The symptoms are most requently associated with fever.
(Members of all the major respiratory virus groups often cause cough and bronchitis,
in fact, cases of acute bronchitis are particularly common during epidemic influenza)
A small number of all cases of acute bronchitis have a nonviral cause.
Mycoplasma pneumoniae and Bordetella pertussis play an important role.
In adolescens and adults Bordetella pertussis has been associated with 12 to 32% of cases.
Also Chlamydia pneumoniae has been associated with cases of acute bronchitis
Treatment
Symptomatic treatment
Treatment of most cases of acute bronchitis is symptomatic and is directed primarily at the
control of cough. Patients do not require hospitalization except in cases of unusual severity
Antimicrobial treatment
Antimicrobial treatment is recommended for cases of acute bronchitis caused by Bordetella
pertussis, Mycoplasma and Chlamydia pneumoniae.
Antimi
Mycoplasma pneumoniae infections are treated with erithromycin or tetracycline.
Bordetella pertussis infections with erythromycin
Chlamydia pneumoniae with tetracycline, erithromycin or azitromycin
Chronic bronchitis and obstructive
pulmonary disease
Chronic bronchitis is a chronic inflammation of the bronchi in the lungs.
It is considered one of the two forms of chronic obstructive pulmonary disease (COPD),
clinically defined as a persistent cough producing sputum and mucus for at least three months
per year. COPD is a severe form characterized as airflow limitation. Occasionally chest pain
fever and malaise may occur.
Superinfections can coexist, causing exacerbation of COPD. Mucus is often green and also
may be orange or pink, depending on the pathogen causing the inflammation.
Epidemiology and etiology of COPD
Over the past several decades, the prevalence of Chronic Obstruc.Pulmon.Dis.
has increased in wordlwide, especially in industrialized countries and in women
Multiple factors can cause COPD:
 tobacco smoking is considered the major cause in industrialized countries
 cystic fibrosis caused by a gene defect in the transmembrane conductance
 immunoglobulin deficiency (IgA or selective IgG subclasses or both)
 structural or acquired defect in cilia
 air pollution
Allergies can also cause mucus hypersecretion, leading to symptoms similar to asthma
or bronchitis
Microrganisms implicated in acute
exacerbation of COPD
An exacerbation of COPD or chronic bronchitis is signaled by an increased
volume of more purulent sputum, cough and dyspnea.
Bacterial bronchial airway colonization includes:
Streptococcus pneumoniae, Haemophilus influenzae, Neisseria ssp.
Also respiratory viruses have been associated with asthmatic exacerbation
(one third were related to viral infections) such as Rhinoviruses, coronaviruses
and parainfluenzaviruses)
Antibiotic therapy
Many consideration must guide the selection of appropriate antibiotic therapy
including spectrum of activity, mechanism of action, tissue penetration,
tolerance of the drug by the patients.
Antimicrobial choice must be made in the context of emerging antibiotics
resistance.
Currently most patients receive:
amoxicillin clavulanate
erithromycin
levofloxacin
Acute pneumonia
Acute pneumonia is the sixth most common cause of death in USA and the most common
cause of infection-related mortality.
A wide number of microbial agents can cause acute pneumonia, and no a single antimicrobial
regiment can be expected to cover all possibilities, because a specific etiologic diagnosis is
often not possible.
In addition the prevalence of antibiotics resistant strains has made this challenge more difficult
This is a section of the lungs in a patient affected by pneumonia.
The neutrophils appear to be floating in space
Etiological agents of acute
pneumonia: bacteria
Streptococcus pneumoniae
Staphylococcus aureus
Anaerobic bacteria: bacteroides,fusobacterium ssp
Haemophilus influenzae
Enterobacteriacee:
Escherichia coli
Klebsiella pneumoniae
Enterobacter
Serratia
Pseudomonas aeruginosa
Legionella pneumoniae
Acinetobacter
Neisseria meningitidis
Less common agents of acute pneumonia:
Fungi, Rickettsia, Chlamydia etc.
Aspergillus ssp
Candida albicans
Candida ssp
Coccidioides immitis
Cryptococcus neoformans
Histoplasma capsulatum
Coxiella burnetii Q fever stands for queer, is a zoonosis (contact with
infected animals
Rickettsia rickettsiae puncture of tick
Chlamydia psittaci caused by infected birds (parrots ducks)
Chlamydia pneumoniae pneumonia often asymptomatic in young p.
Chlamydia trachomatis causes ocular or genital infections
Mycoplasma pneumoniae causes an atypical form of pneumonia in
young population
Causative agents of acute
pneumonia: viruses
Children
Common
Respiratory syncyntial virus
Parainfluenza virus types 1,2,3.
Influenza A virus
Uncommon
Adenovirus, Rhinovirus
Adults
common
Influenza A and B
Uncommon
Rhinovirus
Enterovirus
Community-acquired pneumonia
Acute Community-Acquired pneumonia
A long list of bacterial, fungal, viral agents may cause this syndrome.
Patients with acute community-acquired pneumonia are usually in their mid-fifties to late
sixties.
Peak incidences in midwinter and early spring have been described, so there is no
“pneumonia season” but disease takes place at all time.
Most patients (60% to 90%) have one or more chronic diseases, cardiovascular diseases
neurological diseases, diabetes. Immunosuppression related to myelosuppressive agents
or HIV infection may be present in more than 57% of patients. (patients affected by HIV
infection are treated with myelosuppressive agents and develop pneumonia in many
cases
Acute Community-Acquired
Pneumonia: signs and symptoms
Community-acquired pneumonia presents with a sudden onset of a chill followed by fever
chest pain and cough producing mucopurolent sputum.
The signs, symptoms and physical findings vary according to the age of the patient.
These classic findings in some combination are present in approximately 81% of patients
with community-acquired pneumonia for a mean of 6 days.
Cough is noted in greater than 80 to 90% of patients and is often productive.
A variety of nonrespiratory symptoms are associated with pneumonia, including anorexia,
sweats and nausea.
Tachypnea (more than 30 breaths per minute) is noted in older age groups.
The white blood cells (15,000 to 35,000/mm3), also positivity in C-reactive protein is
noted early
Acute Community-acquired
pneumonia. Signs and symptoms
Acute Community-Acquired
Pneumonia: infectious agents
In the past 50% to 90% of cases were caused by Streptococcus pneumoniae.
More recently the importance of S. pneumoniae has varied showing from 16 to 60%.
Advanced age, cigarette smoking, diabetes, chronic illnesses, have been indicated as
significant risk factors for the development of pneumococcal pneumonia.
An estimated 3% to 38% of cases of ACAP are caused by Haemophilus influenzae
(the true incidence is obscured by the difficulty to isolate it from sputum).
Staphylococcus aureus accounts for 2 to 5% and takes an increase importance in older
patients or in those with influenza.
Gram negative rods account for 7 to 18% of cases. Half of these cases are caused by
Pseudomonas aeruginosa. Gram negative rods are particularly important in hospitalized patients
and immunocompromized patients
Acute Community-Acquired
Pneumonia: infectious agents
S. aureus
Streptococcus pneumoniae
Pseudomonas aeruginosa
Acute Community-Acquired
Pneumonia: other agents
•
•
•
•
•
The importance of Legionella species varies
in different geographic areas.
No clinical signs distinguish legionella
species pneumonia from that caused by
other bacteria
However the presence of a high fever, male
sex, elevated liver enzyme levels, have all
been associated with Legionella
pneumoniae.
Moraxella catarrhalis has been also
identified as a cause of pneumonia.
The incidence is low, but Moraxella
catarrhalis appareas an important pathogen
in older adults with Chronic Obstructive
Pulmonary Disease or in
immunocompromized people.
Moraxella catarrhalis
Community-Acquired Pneumonia:
in the older adults
Pneumonia is the third most common cause for hospitalization in those 65 and older,
and a major cause of morbidity and mortality may be considered.
Fever less commonly in older adults (especially over 80) occurs, temperature is variable,
but tachypnea more frequently is observed.
In general the etiological agents of community acquired pneumonia in older people
are similar to younger populations: S. pneumoniae is the predominant
organism (20 to 60% of cases). H. influenzae is the second most common agent.
Increased oropharyngeal colonization with Gram negative rods has been documented
in the older population, so a predisposition to develop pneumonia has been noted in
these subjects
Community-Acquired Pneumonia:
in Patients with AIDS
Pneumocystis carinii infection remains a significant problem in patients with AIDS.
Many studies suggest that Pneumocystis accounts for over one third of cases of
pneumonia in HIV-positive populations.
The cases of pneumonia can be 100 to 300 times greater in HIV infected patients than in
non-HIV infected controls.
A variety of other microrganisms have been implicated, including:
Rhodococcus equi (intracellular Gram positive organism, it infects animals occasionally
humans are infected, especially immunocompromized patients)
Pseudomonas aeruginosa especially in presence of central venous or urinary catheters.
Mycobacterium tuberculosis and nontuberculous mycobacteria,
Cryptococcus neoformans
Cytomegalovirus
Pneumocystis carinii
Pneumocystis carinii a fungal organism or a protozoa is considered
(unconfirmed taxonomy)
Asymtomatic infection is common in infant (confirmed by level of specific
antibodies in population).
Pneumonia in AIDS patients a riattivation of infection and no a new
infection is considered
Community-Acquired Pneumonia:
in Patients with AIDS
Criptococcus neoformans
Severe Community-Acquired
Pneumonia
Approximately 10% of community acquired pneumonia cases are severe and required
intensive care and/or mechanical ventilation.
Advanced age, presence of other significant diseases (including pulmonary diseases),
congestive heart failure, genetic predisposition, appear to be associated with the
development of severe community-acquired pneumonia.
Streptococcus pneumoniae and Legionella pneumophila are the organisms more
frequently involved.
Gram negative rods, especially klebsiella species must be considered in patients affected
by Chronic Obstructive Pulmonary Diseases, diabetes and in case of alcohol abuse.
Mortality rates have ranged from 20% to 50%.
Severe Community-Acquired
Pneumonia
Klebsiella pneumoniae on Mc Conkey agar
Atypical pneumonia syndrome
In 1938 Hobart Reiman described a mild clinical form of atypical pneumonia
characterized by fever malaise, headache, cough without sputum.
Mycoplasma pneumoniae, Chlamydia pneumoniae, Francisella tularensis and a
variety of respiratory viruses may cause atypical pneumonia.
Mycoplasma pneumoniae infections in the older child (older than 5 years), in the
adolescent and in the young adult occurs. Mycoplasmal infection occurs at all time but,
an increased incidence is noted in the late summer and autumn, in contrast
Adenovirus infection, another cause of atypical pneumonia, most commonly occurs
between January and April
Francisella tularensis
•
Francisella tularensis is Gram negative
intracellular parasyte.
•
It is the etiological agent of tularemia, a
zoonosis called rabbit fever.
•
Bacterium can infect rabbits and other
small animals.
•
Infection can be transmitted to humans
by a puncture of ticks (vector) or by
inhalation of bacteria.
•
Infection of the skin is observed (75-80%
of cases ) after a contact with infected
animals (ulcerated areas)
•
In course of tularemia also a form of
atypical pneumonia occurs.
Antibiotic therapy in CommunityAcquired Pneumonia
The choice of antibiotic is complicated by the increasing incidence of drug resistance in
pneumococci.
The incidence of penicillin nonsusceptibility (MIC ≥0,12) has increased dramatically since the 1970.
Surveillance studies between 1979 and 1987 shoved high levels of incidence of
Penicillin nonsusceptibility. By the early 1990 the incidence has increased to 20% and by
the winter of 1999-2000, 34,1% of pneumococchi strains were nonsusceptible and 16%
were resistant to penicillin (MIC<2).
Oral cephalosporins such as cefuroxime appears to be the most potentially usefull, but
only for penicillin-intermediate strains (from 0,125 to 2) of pneumococci.
Parental penicillin or third-generation cephalosporins (ceftriaxone or cefotaxime) are
used for resistant strains.
Vancomycin, linezolid, quinupristin/dalfopristin are considered when etiologic agent is
meticillin resistant Staphylococcus aureus (MRSA)
Pneumonia prevention
•
•
•
•
Vaccination against influenza virus and against S. pneumoniae serve to prevent pneumonia.
In older adults, influenza vaccine decreases the incidence of pneumonia by 53%.
Pneumococcal polysaccharide vaccine is recommended for patients older than 65.
Protein polysaccharide vaccine is available only for pediatric use (conjiugated vaccine).
Chronic pneumonia
• Chronic pneumonia is a pulmonary parenchymal process caused by infectious or
noninfectious agents, that has been present for weeks to months, characterized by
abnormal radiografic findings and chronic or progressive pulmonary symptoms.
Chronic pneumonia: etiology
The infectious causes of chronic pneumonia can be divided into two main groups:
1)
Agents that typically cause acute pneumonia and are unusual causes of chronic
pneumonia
2)
Infectious agents that typically cause chronic pneumonia.
Many agents typically causing acute pneumonia such as: anaerobic bacteria,
Staphylococcus aureus, Haemophilus influenzae, enterobacteriacee and
Pseudomonas aeruginosa, most likely produce a persistent chronic pneumonia.
This is a chronic necrotizing process that most commonly occurs in patients
with significant diseases (alcoholism, diabetes mellitus, hospitalized patients, individuals
requiring ventilatory assistance etc.)
Chronic pneumonia: etiology
Infectious agents that typically cause chronic pneumonia
Aerobic and anaerobic bacteria:
Actinomyces
responsable of chronic abscesses
Nocardia
Rhodococcus equi
Burkholderia ssp
Mycobacteria (tuberculosis, avium complex)
Fungi:
Aspergillus ssp
Cryptococcus neoformans
Coccidioides ssp
Burkholderia cepacia complex
Burkholderia cepacia complex is a group of Gram negative, catalase positive
and lactose non fermenting species (nine species). This microrganism causes
pneumonia in immunocompromized patients and lung disease in patients
affected by cystic fibrosis or chronic granulomatosis disease.
Pathogenesis: organisms may be found in water or in soil and can survive in wet
areas, also person to person spread has been documented.
Infection can cause a rapid decline in the lung function resulting in death.
B. cepacia complex is naturally resistant to many common antibiotics including
Aminoglicosides or Polimixyn B (used for identification of organism: polymixin
bacitracin lactose agar)
Chronic pneumonia: noninfectious
causes
However it is important to recognize the importance of non infectious causes
of chronic pneumonia including:
Neoplasia (carcinoma, lymphoma etc.)
Drugs
Radiations
Amyloidosis
Sarcoidosis
(deposit of amiloid proteins in organs or tissue such as heart, intestine)
(abnormal collection of inflammatory cells in many organs)
Other idiopathic causes
Chronic pneumonia in people with
AIDS
• In persons with acquired
immunodeficiency syndrome this
infection is frequently seen. In these
patients, chronic pneumonia may be
caused by Rhodococcus equi,
Pneumocystis ssp, Cytomegalovirus
or by noninfectious disorders as
Kaposi’s sarcoma, lymphoma, radiation
therapy etc.
• Since the introduction of antibiotics in
the 1940s, new pathogens have
emerged. Organisms considered to be
commensals are now recognized
as pathogens.
R. equi produces large and mucoid colonies.
Initially the colonies are greyish but after
further incubation may appear salmon in colour.
Chronic pneumonia: therapy
In many patients, etiologic agents do not are identified only on the basis of Gram stain or
cultural methods, but definitive diagnosis requires serologic, histologic, bacteriologic
studies or other diagnostic tests.
In this situation, immediate empirical therapy is recommended, the choice of antimicrobial
agents must be based according to epidemiologic or clinical data.
Empirical therapy with the newer fluoroquinolones (levofloxacin, moxifloxacin
etc) may be performed
In patients, affected by chronic pneumonia, intubated in an intensive care unit,
antimicrobial therapy should provide broad-spectrum coverage against hospital-acquired
flora including anaerobes, Staphylococcus aureus and aerobic Gram negative bacteria
Corticosteroids in chronic
pneumonia
The use of corticosteroids in the treatment of patients with chronic pneumonia is controversial.
Steroids are not indicated in case of pneumonia caused by infectious agent .
Generally corticosteroids only in chronic pneumonia due to noninfectious causes are used.
Cystic fibrosis
Cystic fibrosis is caused by a mutation in the gene encoding for the protein cystic fibrosis
transmembrane conductance regulator (CFTR).
This gene is required to regulate the components of sweat glands, the production of digestive
juices, and mucus. Cystic fibrosis determines superinfections of the lungs, compromizes the
function of the pancreas, liver , intestine, and sex organs.
The mucus clogs the lungs causing breathing problems and bacterial infections with conseguent
lung damage
Cystic fibrosis: clinical
manifestations
The clinical manifestations of cystic fibrosis are related to viscous secretions
and chronic bacterial infection of the lung. More than 90% of cystic fibrosis
deaths are caused by the progressive pulmonary insufficiency.
Most respiratory bacterial infections in adults are caused by Staphylococcus
aureus, Pseudomonas aeruginosa, Burkholderia cepacia complex.
The clinical finding is dominated by a chronic cough characterized by purulent
sputum, dyspnea anorexia and weightless.
Most adults may exhibit low-grade fever, sepsis or bacteremia.
Despite the large number of bacteria in sputum, other complications
(hemoptisis or pneumothorax) frequently occur.
Hemoptisis is expectoration of blood from the bronchi.
Pneumothorax is a collection of air or gas in pleural cavity in course of trauma or
surgical treatment
Cystic fibrosis: other complications
• The pancreas is particularly involved in cystic fibrosis; most patients show a
progressive destruction of organ.
The prevalence of diabetes mellitus increases in adults.
• The diabetic condition increases the predisposition to pulmonary infections
and makes difficult the treatment.
Cystic fibrosis: microbiology
Staphylococcus aureus and Pseudomonas aeruginosa are the primary
etiological agents of pulmonary infection in patients with cystic fibrosis.
S. aureus can be found in about 30% of patients with CF. Antistaphylococcal
penicillins (methicillin and isoxazolil-penicillins) are used to control infections
caused by this microrganism.
Resistance to these antibiotics is increasing in patients with CF (10 to 30% are
infected with methicillin-resistant Staphylococcus aureus MRSA).
A further problem in CF patients with MRSA infection is the emergency of
strains with reduced vancomycin susceptibility
Small colony variants of S. aureus are recognized
with increasing frequency in patients with CF or
chronic osteomyelitis
The variant shows a higher survival to cell
mediated immunity
Cystic fibrosis: microbiology
• More than 80% of adolescent and adult patients with CF, presents a chronic infective
state caused by Pseudomonas aeruginosa.
• Strains of P. aeruginosa isolated from these patients produce a large amounts of
an extracellular mucoid polysaccharide called alginate (mucoid colonies that result
from alginate production are predominant in patient with CF and are rarely seen in
patient with other chronic diseases)
Pseudomonas aeruginosa and
antibiotic resistance
In the early stage of cystic fibrosis infection Pseudomonas aeruginosa strains
are usually susceptible to all antipseudomonal β-lactams, imipenem, quinolones
and aminoglycosides.
Repeated antibiotic treatments and selection of chronic mucoid strains,
Increases antibiotic resistance.
Two factors occur to determine antibiotic resistance:
1) growth as a biofilm
2) growth under anaerobic conditions
Many studies have shown that P. aeruginosa growing as a biofilm is much more
resistant to antibiotics, in addition the capacity to grow under anaerobic
conditions increases the resistance against the aminoglycosides (inactive under
anaerobic conditions)
P. aeruginosa growing under
anaerobic conditions
Proteomic analysis has indicated an outer
membrane protein, upregulated in
anaerobic condition and able to reduce the
accumulation of toxic products of anaerobic
respiration.
Cystic fibrosis: microbiology
• Burkholderia cepacia is an emerging
important nosocomial pathogen
isolated from 10% of patients with CF.
• Many patients with CF and infected
with B. cepacia develop the cepacia
syndrome characterized by a rapid
deficiency of pulmonary function and
bacteremia (these patients die within 6
mounths).
The ability to biofilm formation play an
important role in resistance against
antibiotics.
• Burkholderia cepacia is a frequent
cause of infection in patients with
transplanted lungs.
Cystic fibrosis: microbiology
Other bacteria such as Haemophilus influenzae, Moraxella catarrhalis,
Stenotrophomonas maltophilia and members of enterobacteriacee have been
isolated from the respiratory tract of patients with cystic fibrosis and may play a
role in their pulmonary disease.
In this period, the life expectancy is increasing and more patients with CF
survive, so multidrug-resistant microrganisms such as S. maltophilia are seen
with increased frequency.
The role of Mycobacteria in the lung disease of patients with CF has been
observed. Nontuberculous mycobacteria have been isolated in more than 13%
of patients with CF (72% were Mycobacterium avium complex, 18%
Mycobacterium abscessis)
Cystic fibrosis: (oral therapy)
The aim of therapy is to retard progressive lung demage by removing viscous
and purulent secretions, by bloking person-to-person spread of drug-resistant
organisms frequently noted in CF affected patients.
Antibiotic treatments play a key role in survival. Oral antibiotics can be used to
treat subacute pulmonary exacerbation, despite the presence of
Pseudomonas aeruginosa (resistant to these antibiotics).
Antibacterial therapy, in this case, inhibits the release of toxic bacterial
exoproducts also in absence of bacterial killing.
The emergency of bacterial resistance during monotherapy limits the efficacy
of long-term treatment.
Cystic fibrosis: (parental therapy)
Parental therapy is indicated for clinical exacerbations that do not respond to
oral antimicrobials.
Parental therapy should be guided by bacteriologic analysis of sample and
susceptibity tests to antibiotics.
A combination of antibiotics is indicated to treat infections caused by
Pseudomonas aeruginosa. The pharmacologic regimen usually includes an
aminoglycosides plus another agent active against P. aeruginosa such as a
Cephalosporin (ceftazidime or cefepime).
In case of Staphylococcus aureus infection addition of specific antistaphylococcal agents should be considered
Urinary tract infections:definition
• Urinary tract infection is an infection
regarding the urinary system.
• Urinary system includes the upper
(Kidneys, ureters) and the lower
tract (bladder and urethra).
• Any part of urinary system can
become infected, but most
infections involve the
lower urinary tract (bladder and
urethra).
• Women are at particular risk to
develop urinary tract infection (1:5).
Urinary tract infections: definition
Bacteriuria is a frequently used term to indicate the presence of bacteria in the
urine.
The presence of infected urine in the bladder can be discovered by quantifying
the bacteria in collected urine or in urine obtained via uretral catheterization.
The term “significant bacteriuria” indicates that the number of bacteria
exceeds the number expected from normal contamination.
Asymptomatic bacteriuria refers a significant bacteriuria in patients without
symptoms.
Urinary tract infections
Urinary tract infection may involve only
the lower urinary tract or may involve both
the upper and the lower tract.
Lower urinary tract infections:
cystitis
Cystitis is an infection of the urinary bladder.
This condition more often affects the women, but can regard either sex and all
age groups.
There are several types of cystitis:
1) traumatic bacteria are transferred from the intestinal
tract to the bladder
2) radiation patients treated with radiation therapy
3) hemorragic blood in urines
4) eosinophilic rare form, the bladder wall is infiltrated
with a high number of eosinophils
Cystitis: causes and incidence
Cystitis occurs when the normally sterile lower urinary tract is infected by
bacteria and becomes irritated and inflamed
This condition affects sexually active women ages (20 to 50) but may occur in
not sexually active women or in young girls. Older adults are a high risk for
developing cystitis.
Cystitis is rare in males.
Females are more exposed because of their relatively shorter urethra and the
relatively short distance between the opening of the urethra and the anus
Cystitis: risk factors
Risk of cystitis increases in presence of:
obstruction of the bladder or urethra (congenital abnormalities)
insertion of instruments
Pregnancy
(catheterization or cystoscopy)
(urine discharge becomes difficult)
Diabetes (urines contain more sugar favouring the growth of bacteria)
Analgesic nephropathy (damage induced by use of aspirin, paracetamol)
Reflux nephropathy
(urine is forced back toward the kidney)
Older males develop cystitis associated with a condition of benign
prostatic hyperplasia, prostatitis and abnormalities of urethral structure
Reflux nephropathy
Normally, when the bladder empties, the
ureter closes automatically
In reflux, the valves don’t close and urine
is forced back toward the kidney
Cystitis: infecting organisms
More than 95% of lower urinary tract infection are caused by a single bacterial
species. Escherichia coli is the most frequent infecting organism in acute
forms.
In recurrent urinary tract infections, especially in presence of structural
abnormalities (obstructive uropathy, congenital anomalies) the frequency of
infection caused by Proteus, Pseudomonas, Klebsiella, Enterobacter
enterococci and staphylococci increases
In presence of structural anomalies it is relatively common to isolate
multiple organisms from the urine.
Instrumentation and repeated courses of antimicrobial therapy play an
important role in selection of antibiotic-resistant organisms.
Cystitis: infecting organisms in
hospital environment
The hospital environment influences the etiology of urinary tract infections.
Proteus, Klebsiella, Enterobacter, Pseudomonas ssp, staphylococci and
enterococci are more often isolated from hospitalized patients, on the contrary
E. coli is the most frequent in community.
Cross-infections are important in the pathogenesis of hospital-acquired urinary
tract infections, especially related to catheters introduction.
Corynebacterium urealyticum, staphylococcus saprophyticus and other
coagulase-negative staphylococci have been recognized as important
nosocomial pathogens.
cystitis: symptoms
 Pressure in the lower pelvis
 Painful urination (dysuria)
 Frequent urination (polyuria)
 Need to urinate at night
 Abnormal urine color (cloudy)
 Blood in the urine (hematuria)
 Strong urine odor
Cystitis: tests
In case of cystitis:
• urine analysis
urine analysis commonly shows an
increased number of white blood
cells or red blood cells.
• urine culture
A sample of urine or a speciment
of catheterized urine are collected
for identification of infecting
organism and to select the
specific antibiotic treatment.
Dip slide urine culture device
Cystitis: treatment
Antibiotic treatment is important in the control of infection and
in prevention of recurrent forms.
Conventional therapy
In the past, 7 to 10 days of therapy were recommended for patients with lower
tract infections. In recent years it has become clear that most women have only
a superficial infection and can be treated with shorter courses of therapy,
sometimes with only a single dose of an antimicrobial agent.
Short-Course therapy
Short-course therapy is defined as 3 or fewer days of treatment.
The advantages include a better compliance and a decreased risk for
emergence of multi-resistant organisms in intestinal, urethral or vaginal flora
Cystitis: short-course therapy
Short-course therapy
The most widely used regiments are the oral doses of amoxicillin.
Other regiments include, aminoglycosides, tetracycline, cephalosporins and
fluoroquinolones.
Because of the high cost of the fluoroquinolones and more rapid emergency of
bacterial resistance with their wide-spread use, clinisians may prefer to use
Trimethoprim-sulfamethoxazole. This agent must be used in case of susceptible
infecting organisms or in patients do not receiving recent antimicrobial therapy.
Cystitis: Fungal origin
Candida ssp vary often can cause infection in catheterized patients.
Catheters must be removed in 30 to 40% of subjects with candiduria.
Continuous amphotericin B bladder irrigation or oral fluconazole (200 mg for 7
days) in association with removing catheter serve to eliminate candiduria.
Complicated urinary tract infection
Complicated urinary tract infection indicates an infection caracterized by
functional or structural anomalies (catheters, calculi, malformations).
In general infection in men, pregnant women, children or hospitalized
patients may be considered complicated.
In these cases, relapses or reinfections can occur.
Relapse
is a bacteriuria with the same infecting microrganism.
Reinfection is a bacteriuria with a different microrganism from the original
infecting bacterium.
In patients with complicated infection, infecting microrganisms become
more often resistant to antimicrobial agents.
Reinfection of the urinary lower tract
Many patients can develop frequent reinfections of the urinary lower tract, in
these cases, when symptoms are severe, long-term chemoprophylaxis is
recommended.
If reinfection occurs in course of therapy, the prophylactic agent must be
changed.
Long-term chemoprophylaxis should be considered in patients at risk to
develop renal parenchymal damage (e.g. young children or adults with
obstructive uropathy).
Fluoroquinolones and other antimicrobial agents are used with good
results
Acute pyelonephritis: upper tract
• Acute pyelonephritis describes a clinical syndrome characterized by frank
pain and fever often associated with dysuria, urgency and frequency.
• More frequently this syndrome is accompanied by significant bacteriuria and
acute infection of the kidney
In severe pyelonephritis the Kidney
is enlarged.
Renal surface is covered by
variable numbers of small
yellowish, abscesses surrounded by
zone of hyperemia
Acute pyelonephritis: infecting
organisms
Adhesive properties of the organisms are involved in selection of bacteria able
to colonize and infect upper urinary tract.
Humans studies have confirmed the significance of the adhesive capacity of the
urinary pathogens in pathogenesis of upper tract infections.
Pyelonephritis E. coli strains, adhere more strongly to uroepithelial cells, with
filamentous organelles called pili or fimbriae.
P fimbriae are frequently present in uropathogens E. coli.
In addition to P fimbriae a variety of adhesins have been identified on
uropathogenic E.coli
Other uropathogen microrganisms such as Proteus mirabilis and Klebsiella
ssp. have demonstrated the importance of adherence in pathogenesis of urinary
infections.
Acute pyelonephritis: antimicrobial
therapy
Patients with severe pyelonephritis should be hospitalized.
In patients with acute community-acquired pyelonephritis, when Gram-negative
bacilli are suspected, empirical therapy includes a wide number of antimicrobial
agents: aminoglycosides, piperacillin-tazobactam, third-generation
cephalosporins (cefotaxime or ceftriaxone) or parental fluoroquinolones.
In patients with hospital-acquired Gram-negative infection the possibility to
isolate multi-resistant organisms increases.
Ceftazidime, cefepime, piperacillin-tazobactam, meropenem or ertapenem often
in combination with aminoglycosides are recommended.
Chronic pyelonephritis
• In chronic pyelonephritis one or both
kidneys are involved.
• The anatomo-pathologic exam
shows inflammatory changes in the
pelvic wall, with papillary atrophy.
• The parenchyma shows interstitial
fibrosis with an inflammatory
infiltrate of lymphocytes, plasma
cells and occasionally neutrophils.
Central nervous system syndromes
• The central nervous system may be
infected by a variety of agents,
including viruses, bacteria, fungi,
protozoa.
• In addition a number of
noninfectious disorders may regard
the CNS
such as: neoplastic diseases,
intracranial tumors, vascular
disorders etc.
• All central nervous system diseases
are associated with significant
morbidity and mortality.
Meningitis
Meningitis is an inflammation of the protective membranes covering the brain and spinal cord
(meninges), identified by an abnormal number of white blood cells in cerebrospinal fluid (CSF)
meningitis in acute or chronic form can occur.
Acute meningitis
Acute meningitis is clinically defined as a syndrome characterized by
meningeal symptoms that occur sudden or after several days.
The most common symptoms are severe headache (90% of cases) followed by
nuchal rigidity (70% of cases) associated with fever, confusion, vomiting and
inability to light tolerate (photophobia).
Sometimes especially in small children, only non specific symptoms may be
present such as irritability.
Chronic meningitis is characterized by signs and symptoms lasting for more
than 4 weeks.
Acute meningitis
The acute meningitis syndrome may be caused by a wide variety of infectious
agents but may be caused also by noninfectious agents.
Aseptic meningitis
Viruses are the major cause of the aseptic meningitis syndrome, a term used
to define any meningitis (infectious or noninfectious) for which the etiologic
agent is not defined with stain or cultural methods of CSF and characterized by
lymphocytic pleocytosis.
Acute meningitis: viral agents
Nonpolio enteroviruses
Arboviruses
Herpesviruses
Human immunodeficiency virus
Adenovirus
Parainfluenza virus
Influenza virus
Acute meningitis : major bacterial
agents
Haemophilus influenzae
Neisseria meningitidis
Streptococcus pneumoniae
Listeria monocytogenes mening. occur in extreme ages of life or in AIDS patients, in
pregnant women is associated with risk of miscarriage)
Streptococcus agalactiae colonizes the vaginal and gastrointestinal tract
Staphylococcus aureus and epidermidis
Enterococcus ssp
Propionibacterium acnes
Escherichia coli
Klebsiella pneumoniae
Pseudomonas aeruginosa
Salmonella ssp account for 1% of cases of meningitis in infant and neonates (high mortal.)
Acute meningitis: other bacterial
agents of aseptic meningitis
Rickettsiae
(obligated parasites)
Rickettsia rickettsii zoonotic infection endemic in mediterranean countries
3% of cases develops meningitis
Rickettsia conorii
zoonosis, humans may be infected by a puncture of ticks
Rickettsia prowazekii
trasmetted by pediculi
Spirochetes
Treponema pallidum syphilis agent, meningitis occurs in the first years of infection
Borrelia burgdorferi (Lyme disease) transmissed by infected ticks.
Meningitis occurs in 10-15% of cases
Leptospira ssp zoonotic infection, may be asymptomatic or severe ranging from low
grade fever to meningitis. Diagnosis is performed by serology
Protozoa and Helminths
Community-acquired meningitis
Bacterial meningitis one of the most important disease in worldwide is
considered.
Haemophilus influenzae, Neisseria meningitidis and Streptococcus
pneumoniae, (the tree most common etiological agents) account for more
than 80% of cases.
Surveillance studies conducted during 1995, showed the incidence of bacterial
meningitis decreased. This decrease was a result of vaccination against
Haemophilus influenzae type B (recommended for pediatric use).
Bacterial meningitis is now a disease of adults rather than of infants or
children.
In patients 16 years old or older, community-acquired bacterial meningitis is
caused by S. pneunomiae, N. meningitidis and Listeria monocytogenes
Bacterial meningitis in hospitalized
patients
Bacterial meningitis is also a significant problem in hospitalized patients with
most cases (40%) caused by Gram-negative bacilli (death level about 35%).
The mortality rate for meningitis caused by Enterobacteriaceae is 80%.
More than half of cases in children younger than 24 mounths is caused by
Salmonella, an unusual meningeal pathogen in industrial countries.
In addition bacterial meningitis is a major problem in underdeveloped countries
with 50% of deaths occurring within 48 hours of hospitalization
Bacterial agents of meningitis:
Haemophilus influenzae
Most cases of meningitis caused by
Haemophilus influenzae occur in infants
and children younger than 6 years (incidence
peak of 6 to 12 mounths), with
90% of cases caused by capsular type B
strains.
A significant reduction has been seen in
incidence of invasive infection including
bacterial meningitis caused by H. influenzae
type B in Europe and in United
States.
This decrease is attributed to use of
conjugate vaccine (routine use in children
beginning at 2 mounths of age). The number
of cases has decreased more than
90%.
Bacterial agents of meningitis:
Neisseria meningitidis
Neisseria meningitidis causis meningitis in children and young adults.
Meningococci of serotypes B, C, Y account for most of epidemic diseases.
Serogroup B is frequent in Italy, it accounts for 75% of cases.
Respiratory tract infections, with viruses, such as influenza virus, may play a
role in the pathogenesis of invasive meningocaccal disease.
Patients with deficiencies in the terminal complement components have an
increased incidence of neisserial infection.
An increased risk of invasive meningococcal disease has been observed in
subjects with properdin deficiencies, which suggests a potential role of the
alternative pathway in a complement mediate resistance against meningococci.
Bacterial agents of meningitis:
Neisseria meningitidis
In conclusion because
meningococcal meningitis
occurs in approximately
39% of persons with
complement deficiencies, a
screening test for
complement function
should be performed for all
patients with invasive
meningococcal infection.
Bacterial agents of meningitis:
Streptococcus pneumoniae
Streptococcus pneumoniae is one of the most frequently observed etiologic
agent of bacterial meningitis, it accounts for about 45% of cases.
Streptococci may be divided into more than 90 serotypes, but only 18 are
responsible for 82% of the cases of pneumococcal pneumonia, with a frank
correlation between bacteremic serotypes and those implicated in meningitis.
Meningitidis can derive by cases of pneumonia, otitis media, mastoiditis,
sinusitis ,endocarditis.
Serious infections may be observed in patients affected by:
alcoholism, malnutrition, chronic liver or renal disease, diabetes, multiple
myeloma etc.
Bacterial agents of meningitis:
Streptococcus pneumoniae
Bacterial agents of meningitis:
Listeria monocytogenes
Listeria monocytogenes causes 8% of cases of bacterial meningitis, has been isolated from
land, water, vegetable (infection is often associated with the ingestion of contamined foods)
Listerial infection is most common in infants, in adults older than 60 years,
alcoholics, cancer patients, receiving corticosteroid therapy and immunosuppressed adults.
Pregnant women may present the organism asymptomatically in their genital tract and they
transmit the infection to newnates.
GBNA medium (Gum base nalidixic acid) green-blue colonies
Bacterial agents of meningitis:
Streptococcus agalactiae
Group B Streptococcus
Bacterial agents of meningitis:
Streptococcus agalactiae
Group B Streptococcus, called Streptococcus agalactiae, is a common cause
of meningitis in neonates (52% of all cases), it has been isolated from the
vaginal or rectal cultures of asymptomatic pregnant women.
The risk of trasmission from mother to infant increases on the basis of inoculum
of organisms and on the basis of the number of maternal colonization sites.
Horizontal trasmission has also been documented from the hands of nursery
personnel in hospital.
Group B Streptococcus can also cause meningitis in adults especially in
case of diabetes, cardiac disease, renal failure, corticosteroid therapy.
Bacterial agents of meningitis:aerobic
Gram-negative bacilli
Aerobic Gram-negative bacilli such as Klebsiella ssp, Escherichia coli, Serratia
marcescens, Pseudomonas aeruginosa, Salmonella ssp. are important etiologic
agents of bacterial meningitis. These agents may be isolated from the CSF of
patients after head trauma or neurosurgical procedures and may also be found
in neonates, older adults, immunocompromized patients.
In patients affected by E.coli meningitis, 75% of cases are caused by strains
with K1 antigen. Almost half of pregnant women have this organism
isolated on rectal culture (75% of their infants will be colonized during the first
days of life).
Horizontal trasmission from nursery staff members has also been reported.
Viral meningitis
Enteroviruses are the most important viruses causing meningitis.
Because they are able to escape host defence mechanisms, they may replicate
and disseminate with CNS invasion.
The clinical manifestation of enteroviral meningitis depend on host age and
immune status. In neonates, fever is always present and is accompanied
by any combination of vomiting anorexia, rush and upper respiratory symptoms
and signs.
Nuchal rigidity is present in more than half of patients, expecially in children
in adulescents and in adults.
Photophobia is present in older patients.
Bacterial meningitis: symptoms and
signs
• Patients with bacterial meningitis present fever headache, meningismus
(nuchal rigidity and positivity to Kernig and Brudzinshi signs), accompained by
signs of cerebral dysfunction ranging from lethargy to coma.
• In case of bacterial meningitis in adults the classic triad: fever, nuchal rigidity
and change in mental status was found in two third of patients.
• Some categories of patients may not manifest many of the classic signs of
bacterial meningitis
Diagnosis of bacterial meningitis
For the diagnosis of bacterial meningitis, CSF collected by
lumbar puncture, may be tested.
Typical findings in acute bacterial meningitis are observed:
Opening pressure
200-500 mm H2O
White blood cell count
1000-5000 mm3
Percentage of neutrophils
> 80%
Protein
100-500 mg/dL
Glucose
<40 mg/dL
Gram stain
positive 90%
Culture
positive 85%
Antimicrobial therapy of acute
meningitis
Microorganism
Standard therapy
Haemophilus infl.
β lactamase neg. Ampicillin
Alternative therapies
β lactamase pos.
Neisseria mening
Third gen cephalosporins
Third gen ceph, cefepime,
chloramph.
Cefep, chloramph. Fluoroq.
Penicillin MIC<0,1
Penicillin MIC>2
Penicillin G, ampicillin
Third gen ceph, chloramph.
Vancomycin, third gen.
cephalosporins
Third gen ceph, chloramph.
Penicillin MIC<0,1
Penicillin G, ampicillin
Vancomycin, third gen.
cephalosporins
Penicillin MIC>2
Vancomycin, third gen.
cephalosporins
third gen. Cephalosporins
plus fluoroquinolones
fluoroquinolones
Streptococcus
pneumoniae
Antimicrobial therapy for acute
meningitis
Microorganism
Standard therapy
Alternative therapies
Enterobacteriacee
Third gen. cephalosporins
Pseudomonas aerug.
Ceftazidime or cefepime
Aztreonam, fluoroquinolones,
meropenem
Aztreonam, fluoroquinolones,
meropenem
Listeria monocytogen
Ampicillin or penicillin G
Trimethoprim sulpham.
Streptococcus agalac
Ampicillin or penicillin G
Third gen. Cephalosporins,
vancomycin
Methicillin sensitive
oxacillin
vancomycin
Methicillin resistant
vancomycin
vancomycin
Staphylococcus epid
vancomycin
Staphylococcus aur.
Immunoprophylaxis: Haemophilus
influenzae (recommended vaccination)
Vaccination to prevent infection is a vary useful measure for
decreasing the incidence of bacterial meningitis.
For Haemophilus influenzae type B, the availability of conjugate
vaccines has decreased the number of cases more than 90% in
recent years (conjugate vaccines are effective in reducing
nasopharyngeal colonization).
Three different types of vaccines are licensed for immunization
Immunoprophylaxis: Haemophilus
influenzae (recommended vaccination)
The Hib vaccine is available as:
Hib (alone)
Hib in combination with DTaP (Diphtheria-Tetanus-acellular
Pertussis) vaccine
Hib in combination with recombinant hepatitis B (HBV) vaccine
Immunoprophylaxis: Neisseria
meningitis
Monovalent vaccines using purified serogroup capsular polysaccharides
antigens of Neisseria meningitis have been shown to be immunogenic in
humans.
Serogroup A and C vaccines have demonstrated clinical efficacies of
approximately 85 to 100% in older children and adults (serogroup C component
is poorly immunogenic in recipient younger than 2 years).
The efficacy decreases durung the first 3 years after a single dose.
Vaccination with the quadrivalent meningococcal vaccine (A, C, Y, W135)
is recommended for high risk patients.
Immunoprophylaxis:Streptococcus
pneumoniae
Use of current 23-valent pneumococcal vaccine is recommended for prevention
of bacteremic pneumococcal disease in high risk persons 65 years and older,
with chronic cardiovascular disease, chronic pulmonary disease, diabetes
mellitus, alcoholism, chronic liver disease etc.
Heptavalent conjugate pneumococcal vaccine, administared in four doses
(2, 4, 6, 12 months) is used in children and in infants (efficacy 97%) in
prevention of invasive pneumococcal disease.
Special problems: nosocomial
infections
Nosocomial infections in hospitalization period occur and are a result of
treatmen in hospital or in healthcare service units.
Infections are considered nosocomial if they appear 48 hours or more after
hospital admission or within 30 days after dismission.
Nosocomial infections are known a hospital-acquired infections or
healthcare-associated infection.
Nosocomial infections can cause severe pneumonia, infections of the
urinary tract, bloodstream etc. Many types of infections are difficult to
treat with antibiotics and antibiotic resistance is vary frequent.
Nosocomial infections control
Nosocomial infection control is a discipline developed during the late 1950 to
prevent the problem of nosocomial staphylococcal infections.
The primary role of an infection-control program is to reduce the risk of
hospital-acquired infection transmitted by patients, students and visitors.
The hospital infection control program vary from institution to institution, but,
generally, regards the following areas:
Surveillance
Education
Antimicrobial utilization
Environmental Hygiene
Nosocomial infections
Surveillance
Surveillance for nosocomial infections is generally reserved to areas of the
hospital where the highest rates of infection, highest impact of infection and
antibiotic resistance are likely to be found.
These areas include: intensive care units, cardiothoracic surgery units,
hematology and oncology units.
The importance of surveillance was demonstrated by the reduction in
nosocomial infections in hospitals with active surveillance program, compared
with hospitals without such programs.
Nosocomial infections
Education
A fundamental role in prevention of nosocomial infections is to educate
the hospital staff in specific sections for the control of diseases: sterilization,
disinfection and infection-control policies.
In many hospitals the epidemiology team is responsible for blood-borne
pathogen training and for airborne-isolation-mask training and fit testing.
Nosocomial infections
Antimicrobial utilization
Aboud one-half of hospitalized patients receive antimicrobial agents and their
use varies widely in hospitals.
The hospital epidemiology program should monitor the antimicrobial susceptibility profiles to observe the development of antimicrobial resistance.
The results should be correlated with the antimicrobial agents currently used in
the institution.
Many remedies should be made to optimize antimicrobial prophylaxis for
surgical procedures, optimize the choice of empiric antimicrobial therapy and
improve the antimicrobial prescribing practices
Nosocomial infections
Environmental hygiene
Because most of hospitalized patients has become immunocompromized,
the importance of environmental hygiene has significantly increased.
The control and prevention of environmental infection by hospital
epidemiologists must be considered.
Disinfection, sterilization and control
of hospital environment
A major risk of clinical procedures is the introduction of infections. A failure of
disinfection or sterilization techniques increases not only the risk of person-toperson trasmission (e.g, hepatitis B virus), but also the risk of environmental
pathogens trasmission (e.g. Pseudomonas aeruginosa, Klebsiella pneumoniae).
The use of disinfectants, the sterilization of medical or surgical instruments is
crucial to inhibit the transmission of infectious pathogens to patients.
Disinfection, sterilization and control of
hospital environment: definition of terms
Sterilization:
is a complete suppression or destruction of all forms of microbial
life. Steam under pressure, dry heat, ethylene oxide gas, and liquid chemicals
are the principal sterilizing agents used.
Disinfection:
describes a process that eliminates many or all pathogenic microorganisms with the exception of bacterial spores. The efficacy of disinfection
depends on the level of bacterial contamination, on the nature of objects, on the
presence of biofilms, on the temperature and pH.
Disinfection, sterilization and control of
hospital environment: definition of terms
Disinfection differs from sterilization by the absence of sporicidal property, but
this is an oversimplification. Many disinfectants in fact can kill spores with
prolonged exposure times.
Cleaning
is the removal of visible organic and inorganic materials from objects and
surfaces, using water with detergents or enzymatic products.
Decontamination
is a procedure that removes pathogenic microorganisms from objects.
Disinfection: chemical disinfectants
Alcohol
in the health care setting,
“alcohol” indicates two water-soluble
chemical compounds: ethyl alcohol
and isopropyl alcohol. These
alcohol are rapidly bactericidal
rather than bacteriostatic against
vegetative forms of bacteria, they
are also tuberculocidal, fungicidal,
virucidal, but do not kill bacterial
spores.
Alcohols are not recommended to
sterilize medical and surgical
materials for the absence of
sporicidal action and inability to
penetrate protein-rich materials.
Disinfection: chemical disinfectants
Chlorine and chlorine compounds
Hypochlorites are the most widely used of the chlorine
disinfectants and are available in a liquid or solid form. They
have a broad spectrum of antimicrobial activity (bactericidal,
virucidal, fungicidal, sporicidal, mycobactericidal). Remove dried
or fixed organisms and biofilm from surfaces, with a low
incidence of serious toxicity.
In hospital are used as irrigating agents in endodontic treatment, to
disinfect laundry, dental appliances and water distribution system in
hemodialysis centers and hemodialysis machines.
Disinfection: chemical disinfectants
Hydrogen peroxide
Many reports describe bactericidal, virucidal, sporicidal and fungicidal properties
of hydrogen peroxide, in hospital it has been instilled into urinary drainage bags
to eliminate a source of bladder bacteriuria and environmental contamination.
(this procedure did not reduce catheter associated bacteriuria).
One of the more recent low-temperature plasma sterilizers
is STERRAD system.
It uses hydrogen peroxide vapor and low-temperature gas
plasma to sterilize most clinical devices (hydrogen peroxide
in presence of electric circuit is transformed in plasma state
with production of free radicals).
Disinfection: chemical disinfectants
Iodophors
Iodophors are used for the disinfection of blood-culture bottles and medical
instruments (endoscopes, hydrotherapy tanks).
Antiseptic iodophors are not used such as hard-surface disinfectants.
Iodine or iodine-based antiseptic should not be used on silicone catheters
because the silicone tubes may be damaged.
Disinfection: chemical disinfectants
Quaternary ammonium compounds
The quaternary ammonium compounds are widely used as surface disinfectants.
There have been some reports of infections related to contaminated
quaternary ammonium compounds used to disinfect materials such as
cystoscopes or cardiac catheters (most Gram-negative enterobacteria have
been found to survive or grow in them)
The quaternaries are commonly used in enviromental disinfection of non critical
surfaces such as floors, forniture and walls
Disinfection against emerging
pathogens
Revelant emerging pathogens include: Cryptosporidium parvum
(causes oppurtunistic infections in AIDS patients), Helicobacter pylori (gastritis
and ulcer), E. coli 0157:H7 (is enterohemorrhagic E. coli), HIV, Hepatitis C
virus, Creutzfeld-Jakob prion (causis spongiform encephalopathy), antibioticresistant bacteria such as MRSA (methicillin-resistant Staphylococcus aureus),
multidrug-resistant Mycobacterium tuberculosis and nontuberculosis
mycobacteria.
The susceptibility of each of these pathogens to chemical disinfectants has been
studied. With the exception of prion (see later) standard disinfection procedures
are able to sterilize or disinfect instruments or medical devices
contaminated with blood or other organic fluids from infected persons.
Disinfection against prions
The prions of Creutzfeldt-Jakob disease exhibit an unusuals resistance to
conventional chemical and physical methods.
For high-risk tissues (brain, spinal cord etc), high risk patients and critical
medical devices, is recommended to clean the device and sterilize by one of
four methods.
1)
Immerse in 1N NaOH for 1 hour, remove and rinse in water and autoclave
at 121° C for 1 hour.
2)
Immerse instruments in 1N NaOH for 1 hour and heat in a gravity
displacement sterilizer at 121° C for 30 min.
3)
Autoclave at 134°C for 18 min. in a prevacuum sterilizer.
4)
Autoclave at 132°C for 1 hour in a gravity displacement sterilizer.
Infections caused by percutaneous
intravascular devices
The use of intravascular devices, to deliver sterile fluids, drugs and nutritional
products has increased during the past decades. It is estimated that aboud 50%
of ospitalized patients receive intravenuos therapy with a large risk for local and
systemic blood stream infections.
The use of therapeutic medical devices is often associated with complications.
Vascular catheters have become an increasingly source of bacteremias (from
3% in the mid-1970s to 19% in the early 1990s)
Nosocomial bacteremia caused by
percutaneous intravascular devices
Pathogenesis:
In order of intravascular device-related bacteremia, microrganisms must gain
access to the extraluminal or intraluminal surface of the device. Microbial
adherence and incorporation into biofilms then occurs, resulting first in infection
and then in hemotogenous dissemination.
The figure illustrates the potential points of access to an intravascular device, each
of which is associated with cases of nosocomial bacteremia
Device-related bacteremia can derive by:
health
1) point of insertion of device
2) contamination of the device or attachment of
pathogens on the skin surrounding the insertion site
health care worker
Nosocomial bacteremia caused by
percutaneous intravascular devices:
other infection sources
Contamination may occur in case of defects in container
Contamination may occur in case of malfuntioning air filter
Contamination may occur in case of defect of pressure measuring
devices
Contamination may reach blood stream at the catheter insertion
size
Nosocomial bacteremia caused by percutaneous
intravascular devices: Microbiology
Staphylococci predominate, and are the most frequently isolated pathogens in
device-related infections.
Although Staphylococcus aureus is a frequent cause of device-associated
infections, the coagulase-negative staphylococci have become the most
common causes of these infections in the past two decades, especially in
immunocompromizes patients and when long-term central venous access is
required.
Recent studies have suggested that CN staphylococci may be able to adhere
to plastic catheters more than other microrganisms (ability to biofilm formation).
Staphylococci account for two thirds to 90% of the cases of bacteremia
associated with medical implanted devices.
Microbiology of device-associated Bacteremia:
(other microrganisms)
Coagulase-negative staphylococci including Staphylococcus epidermidis
Staphylococcus aureus
Enterococcus ssp
Serratia marcescens
Candida albicans
Candida tropicalis
Pseudomonas aeruginosa
Klebsiella ssp
Enterobacter ssp
Citrobacter freundii
Corynebacterium ssp
Burkholderia cepacia complex
Microbiology of device-associated Bacteremia:
(other microrganisms)
Recent studies have suggested an increase in catheter-associated infections
caused by Gram-negative bacilli.
The frequent etiology of unusual microrganisms such as: Enterobacter,
Burkholderia, Citrobacter, suggests the possible presence of these
pathogens in hospital environment.
Concomitant use of broad-spectrum antimicrobials expecially in
immunocompromized patients, contributes to increase the number of deviceassociated bloodstream infections produced by a variety of unusual bacterial
and fungal pathogens.
Antibiotic lock prophylaxis
The use of antibiotic lock solution, in which an antibiotic is injected into the catheter lumen
and the solution is left within the lumen for periods of some hours or days has received
attention in the past years. Antibiotic lock therapy in combination with systemic antibiotic is
recommended for prevention of bacteremias related to central venous catheters or implantable
devices, when the catheters are not removed and the infection is due to coagulase-negative
staphylococci, S. aureus or Gram-negative bacilli producing biofilm.
Antibiotic lock solution contains
taurolidine, biocompatible antibiotic,
citrate and anticoagulant agent
Nosocomial respiratory infections
Nosocomial respiratory tract infections are an important cause of mortality and
morbility in world and they account for approximately 15% of all
nosocomial infections.
Generally any respiratory infection, in health care setting, may occur but the
adjective “nosocomial” indicates those acquired within hospitals.
Many viruses such as: Influenza virus, respiratory syncytial virus and
parainfluenza virus can infect hospitalized patients.
Aspergillus ssp, herpes virus and other opportunistic pathogens cause
respiratory tract infections in transplant recipients and other
immunocompromized patients.
Nosocomial pneumonia
Pneumonia is a frequent, severe and costly problem in hospitalized patients.
It accounts for 15% to 20% of nosocomial infections and is second only to
urinary tract infection.
In intensive care units, pneumonia is the number one of nosocomial infections.
Hospital acquired pneumonias account for the majority of deaths
attributed to nosocomial infections
Nosocomial pneumonia
Definition
Nosocomial pneumonias are inflammatory conditions
of the lung parenchyma caused by infectious agents
not present or incubating at the time of admission,
developed 48 to 72 hours after admission to the
hospital.
Accumulation of neutrophils in the distal bronchioles,
alveoli and interstitium of the lung constitutes the
histopathologic report.
In the last decade, definitions that include
positive cultural results have become preferred by
clinical investigators.
Nosocomial pneumonia:risk factors
A number of studies performed during the last years have established a number
of risk factors for nosocomial pneumonia, such as the elderly age.
These subjects show wide compromises in respiratory tract functions, resulting in
respiratory tract obstruction, reduction of the lung volumes, decreased filtration of
inspired air, or decreased clearance of secretion. Sometimes this condition is
associated with other intrinsic
neurologic defects.
Insertion of an endotracheal tube allows
the direct access of microrganisms to the
lower respiratory tract.
Nosocomial pneumonia:etiology
When disease develops within 4 or 5 days of admission or intubation, the
most common etiological agents associated with hospital-acquired
pneumonia are: Haemophilus influenzae, Streptococcus pneumoniae and
Moraxella catarrhalis.
These bacteria probably originate from the oropharyngeal flora present at
admission.
When disease develops after 5 days a large number of pathogens
may be associated with nosocomial pneumonia.
Etiology of nosocomial pneumonia
after 5 days of admission
Staphylococcus aureus
Streptococcus pneumoniae
Haemophilus ssp (predominantly H. influenzae)
Moraxella catarrhalis
enterobacteriaceae
Pseudomonas ssp (predominantly P.aeruginosa)
Acinetobacter ssp
Other enteric Gram negative bacilli
Fungi (predominantly Candida ssp)
Mixed bacteria: coagulase neg Staphylococci,
enterococci, viridans streptococci, Neisseria, anaerobes
Examples of antimicrobial agents recommended for
empirical therapy of nosocomial pneumonia
Microorganisms
Clinical setting
antibiotics
S. aureus
Severe disease before 5
days in absence of risk
factors
Cefotaxime or ceftriaxone or
or
Clindamycin and ciprofloxacin or
Moderate disease in
absence of risk factors
Vancomycin or levofloxacin
Severe disease in
presence of risk factors
Gentamicin or ciprofloxacin plus
S. pneumoniae
H. influenzae
enterobacteriaceae
P. aeruginosa
Acinetobacter ssp
Stenotrophomonas
maltophilia
Burkholderia cepacia
MRSA
or
Moderate disease in
presence of risk factors
Piperacillin/tazobactam or
Imipenem/cilastatin or
meropenem or
piperacillin/tazobactam or
Cefepime or cefotaxime and
vancomycin or linezolid (if MRSA
likely)
Nosocomial urinary tract infections
Urinary tract infection (UTI), is the most common nosocomial infection that
occurs in both hospitals and nursing homes.
In hospitals where the epidemiology has been better investigated, 80% or more
nosocomial UTIs are related to the use of urethral catheters. Another 5% to
10% occur after other genitourinary manipolations.
In this period the widespread use of systemic antibiotics determines an
increasing number of Candida ssp isolated from catheterized urinary tract.
Risk factors for UTIs associated
with catheterization
Many studies have described the risk factors for catheter-associated urinary
tract infections.
 Time of catheterization
 Microbial colonization of the drainage bag
 Diabetes mellitus
 Absence of antibiotic use
 Female sex
 Abnormal serum creatinine
 Errors in catheter care
Time of catheterization
The time of catheterization is the most important risk factor for the
development of catheter-associated infections.
catheterization is required in these cases:
 Surgery (1 to 7 days)
 Urine measurement (serious ill patients 7 to 30 days)
 Urine retention (1 to more than 30 days)
 Urinary incontinence (more than 30 days)
Short-Term Catheterization
Short-term catheterization is vary used in hospital, in fact 15-25% of hospitalized
patients receive a catheter.
Most catheters are applied only for a short time.
Nevertheless, between 10% and 30% of these catheterized patients develop
urinary tract infection.
In short-term catheterized patients, Escherichia coli is the species most
frequently isolated.
Other common organisms are Pseudomonas aeruginosa, Klebsiella
pneumoniae, Proteus mirabilis, Staphylococcus epidermidis, enterococci
and Candida ssp.
Most episodes of bacteriuria in short-time catheterization are caused by a
single
organisms.
Long-term catheterization
Urines of long-term catheterized patients become infected.
Two different situation can occur.
 The incidence of new episodes of UTIs similar to those observed in
short-time catheterized patients (including a wider variety of Gram positive
and Gram negative species.
 The ability of some microbes to persist for weeks or months in the
catheterized urinary tract
Long-term catheterization: microbiology
Two particular types of microorganisms infect the long-term catheterized urinary
tract:
 E. coli
(strains with specific type 1 pilus)
 Providencia stuartii (strains with specific MR/K adhesin)
P. stuartii strains are rarely found outside the catheterized urinary tract
(it uses catheter such as a niche). It causes purple urine bag syndrome
Urine specimens for long-term catheterized patients, show polymicrobial
bacteriuria in more than 95% of cases
Bacteriuria include common uropathogens such as E.coli, Pseudomonas
aeruginosa and Proteus mirabilis
Complications associated with longterm catheterization
The most common complications are:
 Fever
(low-grade)
 Catheter obstructions (caused by bacteria or glycocalix compounds)
 Urinary stones
(P. mirabilis produce urease, which hydrolyzes urea
to ammonia, increasing urine pH and causing crystal-
lization in catheter lumen).
 Chronic renal inflammation common in long-term catheterized persons.
Often chronic pyelonephritis associated
with deformed calices can occur.
 Other complications
urethritis, epididymitis, scrotal abscess etc
Treatment
Asyntomatic catheter-associated bacteriuria should not be treated.
In case of syntomatic bacteriuria, patients generally are treated with the same
antibiotic therapy used to treat bacteriuria from a known or suspected
bacterial species.
Antibiotics should be modified in case of different report by clinical microbiology
laboratory
Surgical and trauma-related wound
infections
Wound infections after surgical procedures may be frequent in hospitals.
The prognosis of surgical and trauma related infections, depend on
the interaction between:
Patients-related factors such as host immunity, nutritional status, presence of
chronic diseases
Procedure-related factors severity of trauma
Microbial factors adherence and invasion of implicated microrganisms
Perioperative antimicrobial prophylaxis
Microbiology of wound infections
Bacterial contamination of the surgical wounds is inevitable.
Despite many techniques have been performed to eliminate this risk,
bacteria can be isolated from wound surface after surgical procedure.
Numerous species have been described as wound pathogens:
Staphylococcus aureus, CN staphylococci, Enterococci, Escherichia coli,
Pseudomonas aeruginosa, Enterobacter, Proteus mirabilis, Klebsiella
pneumoniae, Bacteroides fragilis.
Unusual and hard-to-culture species including: non-tuberculous mycobacteria,
Nocardia species, Legionella species, Mycoplasma hominis etc. are
occasionally implicated.
Source of contamination of surgical
wound
Despite numerous sources of bacterial contamination of surgical wound have
been described, two are the most common the source of contamination.
 The direct contamination of a patient’s endogenous flora at the moment of
surgery, the most common mechanisms is considered.
 Trasmission from contaminated surgical instruments or surgical materials,
contamination from the skin, mucous membranes of operating room staff
have been implicated as potential sources of microbial contamination.
Perioperative antibiotic therapy
Over the past 20 years, the efficacy of antimicrobial prophylaxis in surgical
procedures has been documented.
The interaction between inoculated bacteria and prophylactically
administared antibiotic, is one of the most important determinant for the
positive prognosis of infected wound in surgical procedures.
For example, without antibiotic prophylaxis the referred risk in developing a
Staphylococcus aureus wound infection after cardiac surgery is 15% to 45%
(approximately the frequency of naso-pharingeal colonization).
The success of perioperative prophylaxis correlates directly with the
susceptibility of bacteria to antibiotics