Opportunistic infections

By Dr.Maysaa El Sayed Zaki Professor of Clinical Pathology l Many opportunistic infections are acquired in hospital. Opportunistic infections are a major cause of illness and death in oncology patients and the leading cause of death in recipients of renal transplants. l Severely immunocompromised patients may develop simultaneous infections with several different types of ‘opportunist’ organisms. l Opportunistic infections are the usual cause of death in patients with the acquired immunodeliciency syn­drome (AIDS). ‘OPPORTUNIST’ Organisms l The term ‘opportunist’ is not an exact one. ‘Opportunist’ organisms have three main characteristics: l 1. They are usually organisms of low pathogenicity, e.g. l Pseudomonas aeruginosa l Staph. Epidermidis l Candida albicans l Cytomegalovirus l Pneumocysus carinii l 2. They cause serious infections mainly when the host’s defense mechanisms against infection are impaired, e.g. l In patients receiving treatment for acute leukaemia or lymphoma, recipi­ents of renal or other transplants who are immunosuppressed, and patients with AIDS l 3. They can behave as conventional pathogens’ but under opportunistic condi­tions may cause atypical clinical presenta­tions or disseminated lesions, e.g. l Mycobacterium tuberculosis causing a PUO illness in immunosuppressed patients due to miliary TB or Strongyloides stercoralis causing over­whelming life­threatening infection in a persistently immunosuppressed patient ‘Opportunist’ bacteria l Gram­negative bacilli l Gram­negative bacilli are the most common l ‘opportunist’ pathogens and their sources are either l Endogenous from the patient’s alimentary tract flora, the most frequent source, causing ‘autogenous’ infections (‘self­infections’) l or Exogenous from infected or colonized lesions from other patients or from moist contaminated sites in the hospital environment Cross­infection may be asso­ciated with the spread of Gram­negative bacilli by the hands of hospital staff l There is a high incidence of opportunistic Gram­negative infections in special units such as oncology units, intensive care and special care baby units, neurosurgical units, liver units, renal units and burns units. l Factors that pre­dispose to Gram­negative infections in these units include instrumentation and the frequent administration of antibiotics. l Many of the Gram­negative bacilli are multiple antibiotic resistant and this resistance is often R factor (plasmid) mediated; there may also be ‘cross­infection’ with plasmids mediating ‘en bloc’ multiple antibiotic resistance between different strains of the same species or between strains of different Gram­negative bacterial species. l The epidemiology of infections occurring in inten­sive care units is typical of that seen in special units. Gram­positive bacteria l These are important causes of opportunistic infections although less frequent causes than Gram­negative bacilli. Examples include Strep. pneumeniae in splenectomized children (sometimes causing serious and recurrent infections), Listeria monocytogenes in lymphoma patients, Staph. aureus in neutropenic patients (causing pneumonia and septicaemia) and Staph. aureus or Nocardia asterozdes in chil­dren with chronic granulomatous disease. l Strep. agalactiae (Lancefield group B haemolytic streptococcus) may cause serious infections in low birth weight neonates and may also rarely cause endo­carditis in elderly debilitated patients. l Staph. epidermidis is an increasingly frequent oppor­tunist organism in immunocompromised or debilitated patients who have either an intra­venous infusion or a catheterized urinary tract or continuous ambulatory peritoneal dialysis (CAPD). This staphylococcus is also an important cause of infection in patients with a Spitz­Holter valve, a prosthetic heart valve or a hip joint prosthesis. l Viridans streptococci have also recently been noted to cause septicaemia occasionally in neutropen ic immuno­suppressed patients. Acid­fast bacilli l Mycobacterium tuberculosis in an important ‘opportunist’ causing disseminated lesions in renal transplant and other patients receiving prolonged immunosuppressive drugs and in patients with lymphoma. BCG and some ‘opportunist’ (‘anonymous’) mycobacteria have also caused infections in immunocompromised patients, although these are very rare compared with NI. tuberculosis, for example disseminated life­ threatening infection due to BCG in a child with chronic granulomatous disease. l Mycobacteriuni avium­intracellulare frequent­ly causes disseminated infection in patients with AIDS. Opportunist fungi l Fungal causes of opportunistic infection are rare compared to bacterial causes, but are important causes of life­ threatening infections in persistently immunocompromised patients. Examples include Candida albicans and other Candida species, Pneumocyssis carinii, Aspergillus funugatus and other Aspergillus species, Cryptococcusus neoformans, Mucor, Histoplasma capsulatum and Coccidioides immitis. The latter two fungi are mainly relevant in patients who have, at some time, stayed in the endemic regions of North America. l These infections particularly affect patients with decreased cellu­lar immunity or neutropenia, including those with lvmphomas or sarcoidosis and recipients of renal transplants. l Previous broad­spectrum antibiotic therapy is an important predisposing factor, especially for Candida and Aspergiilus infections. l Serious Candida lesions may develop in pharyngeal— oesophageal, bronchial, renal and endocardial sites, sometimes in association with candidnemia. l Patients who are having peritoneal dialysis can occasionally develop a candida peritonitis. l Aspergillus infection mainly involves the lungs but subsequent dissemina­tion can involve one or more other sites includ­ing the brain, pituitary, kidneys and heart. l Not only may multiple sites become infected by one fungus, but simultaneous infection due to more than one type of fungus may also occur. The mortality rate of opportunistic fungal infections is high, especially in aspergillus infections in immunosuppressed patients. Viral, protozoal and helminth opportunist organisms l Viruses, protozoa and helminths may cause life­threatening infections in patients with impaired cellular immunity including patients with lymphoma, immunosuppressed patients and patients with AIDS OPPORTUNISTIC CONDITIONS l The ‘opportunistic conditions’ present in an individual patient greatly influence the type of infections that the patient may develop. These conditions include: l Impaired host defenses l This is the most important group of ‘opportunistic conditions’. The three main types of impaired general host defenses include severe neutropenia (granulocytopenia), impaired cel­lular immunity and impaired humoral immu­nity (see Table 7.2). l Severe neutropenia is probably the most fre­quent type of impaired host defense mecha­nism encountered in patients who develop hospital acquired (nosocomial) infection and it may result in serious infections. Infections in neutropenic patients are most often bacterial and death often results from either pneumonia or septicaemia. The chances of serious bacterial infections occurring is inversely related to the granulocyte count, when the granulocyte counts are less than 500­1000 per mm3. The risk of infection is also closely related to the duration of severe neutropenia. Virtually all patients tend to develop serious bacterial infections when the blood granulocyte count has remained less than 300 per mm3 for more than 2 or 3 weeks. l Patients with impaired cellular immunity may suffer from ‘intracellular’ (Table 7.2), bacterial, viral, fungal, protozoal or helminth infections and simultaneous infection with different organisms is frequent. l AIDS is now the most common cause of serious impairment of cellular immunity, in the community, in many countries. l An impaired humoral immune response is particularly associated with serious bacterial infections. l Severe impairment of an immunoglobulin response to infection is less frequent in adults than an impaired cellular immune response. l Impaired immunity and disorders affecting phagocytes may be due either to primary (congenital) or secondary (acquired) causes. Congenital immunodeficiency is discussed in Chapter 8 and is much less frequent than impaired host defenses due to acquired caus­es. Secondary causes include: l 2­Extremes of age l e.g. low birth weight neonates and the elderly l 3­Acquired diseases including l Acquired immunodeficiency syndrome (see Chapter 22) l Diseases of the reticuloendothelial system e.g. leukemia, lymphoma, myeloma l Immunoglobulin deficiency associated with disease l e.g. nephrotic syndrome, protein­los­ing enteropathy, severe malabsorption syndrome l Metabolic disease l e.g. diabetes mellitus, uremia, liver failure l Sarcoidosis l 4­Treatment l Cytotoxic and immunosuppressive drugs l e.g. steroids, azathioprine, vincristine and other drugs used in the treatment of cancer and for recipients of trans­plants. l These drugs frequently cause neutropenia and severe immunodeficiency l 5­Radiotherapy l body irradiation for patients receiving bone marrow­ w hole .g .e ) )trans­plants is an extreme example l 6­Instrumentation and surgery l These manipulations impair local mechanical barriers to infection and facilitate the invasion of organisms into the body, e.g. intravenous infusions and CVP lines, indwelling urinary catheters, tracheostomies and IPPR with use of ventilators and humidifiers. l Endogenous infection is most frequent with these invasive procedures but cross­infection is also common. The causative organisms often include multiple antibiotic­ resistant strains of bacteria l 7­Administration of broad­spectrum antibiotics l The giving of broad­spectrum antibiotics to patients with impaired host defences and/or recent instrumentation predisposes to superin­fection by antibiotic­resistant strains of oppor­tunist bacteria, such as Kiebsiella, Pseudomonas or Serraria, of fungi, such as Candida. l NB Immunosuppressed patient + ampicillin = Klebsidla infection (in many patients) l 8­Structural damage to an organ or system l For example, a kidney damaged by calculi or a lung damaged by previous infection provides a nidus for bacteria and other organisms. l 9­Foreign bodies l Implantation of foreign materials also provides a nidus for infection, often by organisms of low pathogenicity. For example, Staph. epidermidis and candida infections of arteriovenous shunts in renal dialysis patients, aortic dacron grafts, intravenous catheters, prosthetic heart valves, etc. DIAGNOSIS OF OPPORTUNISTIC INFECTIONS l Clinical features are often lacking in immuno­compromised patients with infection. Fever is frequently the only obvious feature. However, fever may also be due to non­infective causes including malignancy or drug reactions. l In all febrile patients blood cultures, prefer­ably two or three sets, should be collected before the start of prompt ‘blind’ chemothera­py. l If possible, a urine sample should also be collected for culture before treatment starts. l A clear bacteriological diagnosis, achieved in only 20­40% of patients, is valuable for subse­quent optimal therapy. l Knowledge of the patient's clinical stare, chest X­ray findings, the types of ‘opportunistic conditions’ present, and the local prevalence of ‘opportunist’ organisms may cause certain infections to be suspected. The specimens required for each main type of infection arc included in Table7.1. l Diagnosis of the exact site of infection is frequently difficult in severely neutropenic patients. Signs of infection may be lacking due to deficiency in ‘pus’ cells and impaired inflammatory response. l Common sites of infection that need to be considered include the lungs, pharynx and oesophagus, and peri­anal region. l in some patients, bacteria from the faecal flora enter the blood from the normal gastrointestinal tract. l Although symptoms or signs at a localized site, such as the perianal region, may be minimal, appropriate swabs should be collected in addition to blood and urine cultures. l Physical examination of the chest and chest X­ray may also show only minimal abnormalities when the patient pre­sents with fever, and sputum may not be pro­duced. l A few days after cultures have been collected, and ‘blind’ antibiotic treatment started, there may be little evidence of any clinical response in some patients who have diffuse shadows apparent on a chest X­ray. Unusual opportunist organisms (Tables 7.1—7.3) need serious consideration in these circumstances. l Pneumocystic pneumonia is the most frequent opportunistic infection in patients with AIDS. l Diagnosis of Pneumocystis and other unusual opportunistic lung infections by open lung biopsy is probably the method of choice since adequate samples of tissue can then be examined by silver stains (such as Grocott’s and other stains) to see the characteristic pneumocystis cysts or fungi. l Histology may also reveal infection by Mycobacrerium tuberculosis or cytomegalovirus. l However, open lung biopsy is not practical in many patients and less invasive procedures such as fibreoptic bronchoscopy with the collection of bronchial washings or biopsy material may be considered. l ‘Induced sputum’ samples can be examined by microscopy and culture for fungi and acid­fast bacilli. l An immunofluorescent anti­pneumo­cystis stain or a Grocott’s silver stain of this spu­tum may reveal pneumocvstis infection. l Serological investigations for evidence of infection by Condida albicans (candida anti­gen), Aspergillus furnigatus (aspergillus antigen and precipitins), Crvptococcus neoforinans (cryptococcal antigen), cytomegalovirus (CMV, CFT), Legionella pneumophila (fluores­cent legionella antibodies), and other opportunist organisms are useful when paired sera show a rising ‘specific’ antibody titre of four­fold or greater, or a single high titre or a positive antigen test. l A positive specific 1gM anti­body result is particularly helpful if cytomegalovirus or legionella infection is sus­pected. l However, these antibody tests are fre­quently unhelpful since ‘false negative’ or only low serum antibody titers result in some patients with established infections, because the immune response is too poor to generate significant antibody titers. l Molecular biology tests are likely to have an important role in future for the diagnosis of certain opportunistic infections such as pneu­mocystis and cytomegalovirus disease l PREVENTION OF OPPORTUNISTIC INFECTIONS l Any impairment of general host defences by treatment is kept under regular review so that the lowest dosage of immunosuppressive drugs, such as steroids, are used for the short­est possible duration that is compatible with effective treatment of the non­infective condi­tion. The main preventive measures include the follow­ing. l 1. High standards of asepsis and antisepsis l Special care is necessary to avoid iniection when putting up intravenous infusions, insert­ing CVP lines, performing peritoneal dialysis or other forms of instrumentation. l 2. Agreed antimicrobial drug policy and prophylaxis l a. Systemic drugs l The use of systemic broad­spectrum antibi­otics in special units should be reduced to a minimum. However, some authorities have suggested the use of ciprofloxacin for the prophylaxis of bacterial infections in neutropenic patients. l This antibiotic is not active against Bacteroides in the normal flora of the gut so ‘colonization resistance’ against some hospital pathogens may be maintained. l Constant bacteriological monitoring of the pathogens isolated from clinical specimens from patients in special units is necessary with particular attention to the current antibiotic sensitivity patterns. l It may be necessary to temporarily ‘ban’ the use of certain antibiotics in a special unit which are associated with a high incidence of antibiotic resistance in the unit. l With bone marrow transplant patients, prolonged prophylaxis with cotrimoxazole may be indicated to prevent pneumocystis lung infection. l b. Oral non_absorbable drugs l Administration or oral non­absorbable drugs may help to prevent septicaemia and anorectal abscesses in patients during the treatment of acute leukaemia while severe neutropenia is occurring. l Various mixtures have been recom­mended including FRACON (a combination of framycetin , colistin and nystatin, used in Britain). These oral drugs (ocasionally sup­plemented by sterile topical antiseptics, such as chlorhexidine, applied to the external surfaces including the perineum and lower genital tract in the female) are given to reduce the gut flora which is the usual source of ‘self­ infec­tions’ in patients with granulocyte counts less than 500 per mm. l c. Prophylactic anti—tuberculous or antihelminth, drugs l In persistently immunosuppressed patients who are known to have had TB in the past, or who have come from a strongyloides endemic geographical area, there is a reasonable indica­tion for prophylaxis with anti­tuberculous drugs or thiahendazole, respectively. l . l 3. Protective isolation l A single room is preferable for leukaemic or transplant patients expected to develop severe neutropenia during treatment and protective isolation procedures are desirable. l The hospital staff of the compromised patient should not also nurse other patients with TB or varicella­zoster infections, unless they are definitely known to have immunity to these infections. l These infected patients should be adequately separated from compromised patients. If an accidental contact occurs between the susceptible compromised patient and a person with measles or varicella­zoster infection, prophylaxis with the appropriate immunoglobulin should immedi­ately be given. l Patients who have severe and persistent immunodeficiency states or who are being immunosuppressed, including irradiated and immunosuppressed recipients of bone marrow transplants, may require complete positive pressure protective isolation. l Patients with malignant disease who are having anticancer chemotherapy should not be given salads or uncooked vegetables which may be a source of Gram­negative bacilli that may colonize the gut Thank You l