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Transcript
 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
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







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.
 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.
 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
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
 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.
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
 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
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 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
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 may be devided into: upper and lower tract
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.
 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.
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.
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
Bacterial
Streptococcus
pyogenes
Infectious
mononucleosis
<1
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
40
Mycoplasmal
Mycoplasma
pneumoniae
Unknown
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.
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
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
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





•
•
•
Staphylococcus aureus causes pharyngitis
expecially in children (1% of cases)
Staphylococcal pharyngitis is
characterized by:
Mucopurulent drainage
Mucosal erythema
Localized pustules
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.
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 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.
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
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 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: 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 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 (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.
The most frequent cause of chronic otitis externa is chronic suppurative otitis media
with perforated tympanic membrane.
Rare causes include: tubercolosis, syphilis and sarcoidosis.
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 is defined by the presence of fluid in the middle ear accompanied by signs or
symptoms
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
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
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
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
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 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)
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
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 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 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 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.
 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: 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, 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 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.
 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.
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.
 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
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 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.


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
 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)
 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 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
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
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
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
 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


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




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

S. aureus
Streptococcus pneumoniae
Pseudomonas aeruginosa
•
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




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





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 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
Criptococcus neoformans
 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%.
Klebsiella pneumoniae on Mc Conkey agar
 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 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.








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)



•
•
•
•
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 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.

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.)
 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 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)
 However it is important to recognize the importance of non infectious causes
 of chronic pneumonia including:
 Neoplasia (carcinoma, lymphoma etc.)
 Drugs
 Radiations
 Amyloidosis
(deposit of amiloid proteins in organs or tissue such as heart,
intestine)
 Sarcoidosis
(abnormal collection of inflammatory cells in many organs)
 Other idiopathic causes
•
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.
 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
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 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
 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
•
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.








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
•

•



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)




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)

 Proteomic analysis has indicated an outer
 membrane protein, upregulated in
 anaerobic condition and able to reduce the
 accumulation of toxic products of anaerobic
 respiration.
•
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.
 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)
 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.




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 antistaphylo coccal agents should be considered
•
•
•

•
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).
 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 infection may involve only
the lower urinary tract or may involve both
the upper and the lower tract.
 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 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







Risk of cystitis increases in presence of:
obstruction of the bladder or urethra (congenital abnormalities)
insertion of instruments (catheterization or cystoscopy)
Pregnancy
(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
Normally, when the bladder empties, the
ureter closes automatically
In reflux, the valves don’t close and urine
is forced back toward the kidney







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.
 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.
 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

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
 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
 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.
 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 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.
 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 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
 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.
 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.
•
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.
•
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 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 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.
 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.
Nonpolio enteroviruses
Arboviruses
Herpesviruses
Human immunodeficiency virus
Adenovirus
Parainfluenza virus
Influenza virus
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.)
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








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 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










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%.
 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.
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.








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.
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
Group B Streptococcus
 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.
 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.
 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.
•
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
 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%
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
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.
 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
 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
 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.
 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.
 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 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
 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.
 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.
 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
susceptibi lity 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
 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.
 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-
to person 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.
 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 microorga nisms 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 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.
 Alcohol

in the health care setting,
“alcohol” indicates two watersoluble 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.
 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.
 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).
 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.
 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
 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.

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.
 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)

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
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
 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.
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





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.
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 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.
 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
 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.







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.
 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.
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
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)
 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.

 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
 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 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.
 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
 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
 The most common complications are:
 Fever
(low-grade)
 Catheter obstructions (caused by bacteria or glycocalix compounds)
 Urinary stones

crystal-
(P. mirabilis produce urease, which hydrolyzes urea
to ammonia, increasing urine pH and causing
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
 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
 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
 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.
 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.
 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