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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