Anaerobic pleuropulmonary infection.

Obligate anaerobes are the predominant constituents of normal oropharyngeal flora and produce pleuropulmonary infection in patients who are prone to aspirate. Obtaining material from these patients for culture from the site of infection that is uncontaminated by normal flora is problematic. In-vitro cultivation of obligate anaerobes requires rigorous anaerobic techniques and susceptibility testing of obligate anaerobes is not standardized in many clinical microbiology laboratories. Few clinical trials of drugs have been done in patients with laboratory documented or putative anaerobic pulmonary infection. For these reasons the diagnosis and therapy of anaerobic pulmonary infection are frequently empirical and guided by published studies of in-vitro activity against collected clinical isolates. Several new drugs that have in-vitro activity against obligate anaerobes have recently become available for empirical treatment of pneumonia.

Pharmacodynamics of antibacterial drugs.

Pharmacodynamics of antibacterial agents relates the time course of drug concentration to its antimicrobial effects at the infection site. Antibacterial agents can be divided into three groups based on pharmacodynamic characteristics: agents that exhibit concentration-dependent bactericidal activity over a range of drug concentrations (e.g., aminoglycosides and fluoroquinolones); agents that exhibit time-dependent bactericidal activity that has little relationship to the magnitude of concentration, provided the concentrations are above a minimally effective level (e.g., beta-lactam antibiotics and vancomycin); and agents that exhibit a predominantly bacteriostatic effect. Knowledge of antimicrobial pharmacodynamics provides a rational basis for determining optimal regimens of dosage amounts and length of dosage intervals.

Cephalosporins, carbapenems, and monobactams.

Nonpenicillin beta-lactams exhibit a variable spectrum of antimicrobial activity, have a wide range of clinical uses and a favorable safety profile. Cefepime's twice-daily dosage and increased activity against Enterobacteriaceae may offer some advantages over older cephalosporins. The carbapenems offer a broad antimicrobial spectrum, and meropenem has an improved safety profile compared with imipenem. Aztreonam is a useful alternative for patients with aerobic gram-negative infections who are allergic to penicillin. The emergence of resistant organisms, however, is an increasing problem with the frequent use of these antibiotics.

Risk factors for infective endocarditis: oral hygiene and nondental exposures.

BACKGROUND: The risks of infective endocarditis (IE) associated with various conditions and procedures are poorly defined. METHODS AND RESULTS: This was a population-based case-control study conducted in 54 Philadelphia, Pa-area hospitals from 1988 to 1990. Community-acquired IE cases unassociated with intravenous drug use were compared with matched community residents. Subjects were interviewed for risk factors. Diagnoses were confirmed by expert review of medical record abstracts with risk factor data removed. Cases were more likely than controls to suffer from prior severe kidney disease (adjusted OR [95% CI]=16.9 [1.5 to 193], P:=0.02) and diabetes mellitus (adjusted OR [95% CI]=2.7 [1.4 to 5.2], P:=0.004). Cases infected with skin flora had received intravenous fluids more often (adjusted OR [95% CI]=6.7 [1.1 to 41], P:=0.04) and had more often had a previous skin infection (adjusted OR [95% CI]=3.5 [0.7 to 17], P:=0.11). No association was seen with pulmonary, gastrointestinal, cardiac, or genitourinary procedures or with surgery. Edentulous patients had a lower risk of IE from dental flora than patients who had teeth but did not floss. Daily flossing was associated with a borderline decreased IE risk. CONCLUSIONS: Within the limits of the available sample size, the data showed that IE patients differ from people without IE with regard to certain important risk factors but not regarding recent procedures.

Dental and cardiac risk factors for infective endocarditis. A population-based, case-control study.

BACKGROUND: Although antibiotic prophylaxis against infective endocarditis is recommended, the true risk factors for infective endocarditis are unclear. OBJECTIVE: To quantitate the risk for endocarditis from dental treatment and cardiac abnormalities. DESIGN: Population-based, case-control study. SETTING: 54 hospitals in the Philadelphia area. PATIENTS: Persons with community-acquired infective endocarditis not associated with intravenous drug use were compared with community residents, matched by age, sex, and neighborhood of residence. MEASUREMENTS: Information on demographic characteristics, host risk factors, and dental treatment was obtained from structured telephone interviews, dental records, and medical records. RESULTS: During the preceding 3 months, dental treatment was no more frequent among case-patients than controls (adjusted odds ratio, 0.8 [95% CI, 0.4 to 1.5]). Of 273 case-patients, 104 (38%) knew of previous cardiac lesions compared with 17 controls (6%) (adjusted odds ratio, 16.7 [CI, 7.4 to 37.4]). Case-patients more often had a history of mitral valve prolapse (adjusted odds ratio, 19.4 [CI, 6.4 to 58.4]), congenital heart disease (adjusted odds ratio, 6.7 [CI, 2.3 to 19.4]), cardiac valvular surgery (adjusted odds ratio, 74.6 [CI, 12.5 to 447]), rheumatic fever (adjusted odds ratio, 13.4 [CI, 4.5 to 39.5]), and heart murmur without other known cardiac abnormalities (adjusted odds ratio, 4.2 [CI, 2.0 to 8.9]). Among case-patients with known cardiac lesions--the target of prophylaxis--dental therapy was significantly (P = 0.03) less common than among controls (adjusted odds ratio, 0.2 [CI, 0.04 to 0.7] over 3 months). Few participants received prophylactic antibiotics. CONCLUSIONS: Dental treatment does not seem to be a risk factor for infective endocarditis, even in patients with valvular abnormalities, but cardiac valvular abnormalities are strong risk factors. Few cases of infective endocarditis would be preventable with antibiotic prophylaxis, even with 100% effectiveness assumed. Current policies for prophylaxis should be reconsidered.

Prevention of bacterial endocarditis: recommendations by the American Heart Association.

OBJECTIVE: To update recommendations issued by the American Heart Association last published in 1990 for the prevention of bacterial endocarditis in individuals at risk for this disease. PARTICIPANTS: An ad hoc writing group appointed by the American Heart Association for their expertise in endocarditis and treatment with liaison members representing the American Dental Association, the infectious Diseases Society of America, the American Academy of Pediatrics and the American Society for Gastrointestinal Endoscopy. EVIDENCE: The recommendations in this article reflect analyses of relevant literature regarding procedure-related endocarditis, in vitro susceptibility data of pathogens causing endocarditis, results of prophylactic studies in animal models of endocarditis and retrospective analyses of human endocarditis cases in terms of antibiotic prophylaxis usage patterns and apparent prophylaxis failures. MEDLINE database searches from 1936 through 1996 were done using root words endocarditis, bacteremia and antibiotic prophylaxis. Recommendations in this document fall into evidence level III of the U.S. Preventive Services Task Force categories of evidence. CONSENSUS PROCESS: The recommendations were formulated by the writing group after specific therapeutic regimens were discussed. The consensus statement was subsequently reviewed by outside experts not affiliated with the writing group and by the Science Advisory and Coordinating Committee of the American Heart Association. These guidelines are meant to aid practitioners but are not intended as the standard of care or as a substitute for clinical judgment. CONCLUSIONS: Major changes in the updated recommendations include the following: (1) emphasis that most cases of endocarditis are not attributable to an invasive procedure; (2) cardiac conditions are stratified into high-, moderate- and negligible-risk categories based on potential outcome if endocarditis develops; (3) procedures that may cause bacteremia and for which prophylaxis is recommended are more clearly specified; (4) an algorithm was developed to more clearly define when prophylaxis is recommended for patients with mitral valve prolapse; (5) for oral or dental procedures the initial amoxicillin dose is reduced to 2 g, a follow-up antibiotic dose is no longer recommended, erythromycin is no longer recommended for penicillin-allergic individuals, but clindamycin and other alternatives are offered.

Prevention of bacterial endocarditis. Recommendations by the American Heart Association.

OBJECTIVE: To update recommendations issued by the American Heart Association last published in 1990 for the prevention of bacterial endocarditis in individuals at risk for this disease. PARTICIPANTS: An ad hoc writing group appointed by the American Heart Association for their expertise in endocarditis and treatment with liaison members representing the American Dental Association, the Infectious Diseases Society of America, the American Academy of Pediatrics, and the American Society for Gastrointestinal Endoscopy. EVIDENCE: The recommendations in this article reflect analyses of relevant literature regarding procedure-related endocarditis, in vitro susceptibility data of pathogens causing endocarditis, results of prophylactic studies in animal models of endocarditis, and retrospective analyses of human endocarditis cases in terms of antibiotic prophylaxis usage patterns and apparent prophylaxis failures. MEDLINE database searches from 1936 through 1996 were done using the root words endocarditis, bacteremia, and antibiotic prophylaxis. Recommendations in this document fall into evidence level III of the US Preventive Services Task Force categories of evidence. CONSENSUS PROCESS: The recommendations were formulated by the writing group after specific therapeutic regimens were discussed. The consensus statement was subsequently reviewed by outside experts not affiliated with the writing group and by the Science Advisory and Coordinating Committee of the American Heart Association. These guidelines are meant to aid practitioners but are not intended as the standard of care or as a substitute for clinical judgment. CONCLUSIONS: Major changes in the updated recommendations include the following: (1) emphasis that most cases of endocarditis are not attributable to an invasive procedure; (2) cardiac conditions are stratified into high-, moderate-, and negligible-risk categories based on potential outcome if endocarditis develops; (3) procedures that may cause bacteremia and for which prophylaxis is recommended are more clearly specified; (4) an algorithm was developed to more clearly define when prophylaxis is recommended for patients with mitral valve prolapse; (5) for oral or dental procedures the initial amoxicillin dose is reduced to 2 g, a follow-up antibiotic dose is no longer recommended, erythromycin is no longer recommended for penicillin-allergic individuals, but clindamycin and other alternatives are offered; and (6) for gastrointestinal or genitourinary procedures, the prophylactic regimens have been simplified. These changes were instituted to more clearly define when prophylaxis is or is not recommended, improve practitioner and patient compliance, reduce cost and potential gastrointestinal adverse effects, and approach more uniform worldwide recommendations.

Prevention of bacterial endocarditis. Recommendations by the American Heart Association.

OBJECTIVE: To update recommendations issued by the American Heart Association last published in 1990 for the prevention of bacterial endocarditis in individuals at risk for this disease. PARTICIPANTS: An ad hoc writing group appointed by the American Heart Association for their expertise in endocarditis and treatment with liaison members representing the American Dental Association, the Infectious Diseases Society of America, the American Academy of Pediatrics, and the American Society for Gastrointestinal Endoscopy. EVIDENCE: The recommendations in this article reflect analyses of relevant literature regarding procedure-related endocarditis, in vitro susceptibility data of pathogens causing endocarditis, results of prophylactic studies in animal models of endocarditis, and retrospective analyses of human endocarditis cases in terms of antibiotic prophylaxis usage patterns and apparent prophylaxis failures. MEDLINE database searches from 1936 through 1996 were done using the root words endocarditis, bacteremia, and antibiotic prophylaxis. Recommendations in this document fall into evidence level III of the US Preventive Services Task Force categories of evidence. CONSENSUS PROCESS: The recommendations were formulated by the writing group after specific therapeutic regimens were discussed. The consensus statement was subsequently reviewed by outside experts not affiliated with the writing group and by the Science Advisory and Coordinating Committee of the American Heart Association. These guidelines are meant to aid practitioners but are not intended as the standard of care or as a substitute for clinical judgment. CONCLUSIONS: Major changes in the updated recommendations include the following: (1) emphasis that most cases of endocarditis are not attributable to an invasive procedure; (2) cardiac conditions are stratified into high-, moderate-, and negligible-risk categories based on potential outcome if endocarditis develops; (3) procedures that may cause bacteremia and for which prophylaxis is recommended are more clearly specified; (4) an algorithm was developed to more clearly define when prophylaxis is recommended for patients with mitral valve prolapse; (5) for oral or dental procedures the initial amoxicillin dose is reduced to 2 g, a follow-up antibiotic dose is no longer recommended, erythromycin is no longer recommended for penicillin-allergic individuals, but clindamycin and other alternatives are offered; and (6) for gastrointestinal or genitourinary procedures, the prophylactic regimens have been simplified. These changes were instituted to more clearly define when prophylaxis is or is not recommended, improve practitioner and patient compliance, reduce cost and potential gastrointestinal adverse effects, and approach more uniform worldwide recommendations.

An assessment of the usefulness of the Duke criteria for diagnosing active infective endocarditis.

We evaluated the usefulness of the Duke criteria for diagnosing cases of active infective endocarditis (IE). Patients were identified prospectively over a 3-year period at 54 hospitals in the Philadelphia metropolitan area. Three of us independently reviewed abstracted hospital records and classified 410 patients as definite, probable, or possible cases of IE or as probable noncases. We then applied the Duke criteria to this sample to assess the degree of agreement between our diagnoses and the diagnoses based on these new criteria. Agreement was good to excellent, ranging from 72% to 90%, depending on the case definition used. The sensitivity of the Duke criteria was also good to excellent, varying from 71% to 99%, again depending on case definition used. Specificity was lower (0-89%). We conclude that use of the Duke criteria will result in little underdiagnosis of IE but that it may result in overdiagnosis of IE; therefore, these criteria should be applied prospectively to determine their clinical usefulness.

Prevention of bacterial endocarditis: recommendations by the American Heart Association.

OBJECTIVE: To update recommendations issued by the American Heart Association last published in 1990 for the prevention of bacterial endocarditis in individuals at risk for this disease. PARTICIPANTS: An ad hoc writing group appointed by the American Heart Association for their expertise in endocarditis and treatment with liaison members representing the American Dental Association, the Infectious Diseases Society of America, the American Academy of Pediatrics, and the American Society for Gastrointestinal Endoscopy. EVIDENCE: The recommendations in this article reflect analyses of relevant literature regarding procedure-related endocarditis, in vitro susceptibility data of pathogens causing endocarditis, results of prophylactic studies in animal models of endocarditis, and retrospective analyses of human endocarditis cases in terms of antibiotic prophylaxis usage patterns and apparent prophylaxis failures. MEDLINE database searches from 1936 through 1996 were done using the root words endocarditis, bacteremia, and antibiotic prophylaxis. Recommendations in this document fall into evidence level III of the US Preventive Services Task Force categories of evidence. CONSENSUS PROCESS: The recommendations were formulated by the writing group after specific therapeutic regimens were discussed. The consensus statement was subsequently reviewed by outside experts not affiliated with the writing group and by the Science Advisory and Coordinating Committee of the American Heart Association. These guidelines are meant to aid practitioners but are not intended as the standard of care or as a substitute for clinical judgment. CONCLUSIONS: Major changes in the updated recommendations include the following: (1) emphasis that most cases of endocarditis are not attributable to an invasive procedure; (2) cardiac conditions are stratified into high-, moderate-, and negligible-risk categories based on potential outcome if endocarditis develops; (3) procedures that may cause bacteremia and for which prophylaxis is recommended are more clearly specified; (4) an algorithm was developed to more clearly define when prophylaxis is recommended for patients with mitral valve prolapse; (5) for oral or dental procedures the initial amoxicillin dose is reduced to 2 g, a follow-up antibiotic dose is no longer recommended, erythromycin is no longer recommended for penicillin-allergic individuals, but clindamycin and other alternatives are offered; and (6) for gastrointestinal or genitourinary procedures, the prophylactic regimens have been simplified. These changes were instituted to more clearly define when prophylaxis is or is not recommended, improve practitioner and patient compliance, reduce cost and potential gastrointestinal adverse effects, and approach more uniform worldwide recommendations.

Gastrointestinal tract colonization with vancomycin-resistant Enterococcus faecium in an animal model.

Vancomycin-resistant enterococci have become important nosocomial pathogens in many institutions. The gastrointestinal tract of susceptible hosts serves as the likely reservoir from which the organism is disseminated. To study factors promoting colonization and the efficacy of decontamination therapy with antimicrobial agents, a model of gastrointestinal colonization with vancomycin-resistant Enterococcus faecium was developed in CF1 mice. At baseline, all animals were colonized with non-vancomycin-resistant enterococci (5.0 log10 CFU/g), but vancomycin-resistant organisms were not detectable. Following gastric inoculation with 5 x 10(8) CFU of a clinical isolate of vancomycin-resistant E. faecium, the strain transiently colonized the gastrointestinal tract of 100% of mice but was undetectable by Day 14 (< or = 2.7 log10 mean CFU/g). In animals who received 5 mg of streptomycin per ml or 250 micrograms of vancomycin per ml in drinking water, colonization with the organism occurred at significantly higher bacterial counts than in controls at 7 days following inoculation (9.4 for vancomycin, 9.2 for streptomycin, and 5.1 log10 mean CFU/g for controls; P < 0.05). Fecal concentrations of vancomycin-resistant E. faecium persisted at high counts through Day 22 in mice receiving these antibiotics, but low counts were also still detected in 3 of 10 control animals. In mice with previously established vancomycin-resistant E. faecium colonization, oral administration of ramoplanin, a lipoglycodepsipeptide to which the strain was susceptible, suppressed growth of all enterococci in feces, including the vancomycin-resistant strain after 7 days of therapy (< or = 3.1 and < or = 3.3 log10 mean CFU/g for vancomycin and streptomycin groups, respectively). All mice had a recurrence of colonization with vancomycin-resistant E. faecium after the ramoplanin was discontinued. In summary, this animal model demonstrates the importance of antibiotics in predisposing to gastrointestinal colonization with vancomycin-resistant Enterococcus spp. Although treatment with ramoplanin temporarily suppressed the organism, recurrence of colonization due to relapse or reinfection occurred.

Incidence of infective endocarditis in the Delaware Valley, 1988-1990.

This population-based study aimed to determine the incidence of native, prosthetic, and bioprosthetic valve nosocomial infective endocarditis (IE), and IE associated with the use of injected drugs. Patients with IE during 27 months over the years 1988 to 1990, and residing in any of 6 counties in the Philadelphia metropolitan area were identified. An expert panel reviewed all patients to verify the diagnosis. Incidence rates were estimated after adjustment for failure to recruit and underreporting. Of 853 potential patients, 670 (79%) met the inclusion criteria. The overall incidence rate of IE was 11.6 cases/100,000 person-years (95% confidence interval [CI] 10.8 to 12.4). The rates for specific types of IE were: 4.45 (95% CI 3.97 to 4.94) for community-acquired native valve, 0.94 (95% CI 0.72 to 1.12) for prosthetic valve, 0.94 (95% CI 0.71 to 1.16) for nosocomial, and 5.34 (95% CI 4.80 to 5.87) for IE associated with use of injected drugs. Previous population studies found overall incidence rates of 1.7 to 4 cases/100,000 person-years, similar to our rate for community-acquired native valve IE. Type-specific rates have not been previously reported. The higher overall rate in this study is partly related to the high prevalence of injection drug use in our area.

Pharmacodynamics of antimicrobial agents. Bactericidal and postantibiotic effects.

Pharmacodynamics of an antimicrobial agent relate the time course of concentrations of the drug to the antimicrobial effects at the site of infection. Antimicrobial agents can be divided into three main groups, based on antimicrobial pharmacodynamic characteristics: 1) agents that exhibit concentration-dependent bactericidal activity over a wide range of drug concentrations (e.g., the aminoglycosides and fluoroquinolones); 2) agents that exhibit time-dependent bactericidal activity that has little relationship to the magnitude of the drug concentrations, as long as the concentrations are above a minimally effective level (e.g., vancomycin and beta- lactam antibiotics); and 3) agents that exhibit predominantly a bacteriostatic effect. Knowledge of the antimicrobial pharmacodynamic characteristics provides a more rational basis for determination of optimal dosing regimens in terms of size of the dose and length of the dosing interval.

Activity of cefepime against ceftazidime-resistant gram-negative bacilli using low and high inocula.

Cefepime is a broad-spectrum cephalosporin that is reported to have enhanced activity against ceftazidime-resistant Gram-negative bacilli. In this study the effects of varying inoculum size on in-vitro susceptibility to cefepime and other selected antimicrobial agents were determined by agar dilution MICs and in time-kill studies. Among strains of Pseudomonas aeruginosa (n = 55) and Enterobacter spp (n = 56) that had previously been identified as ceftazidime-resistant, 73% and 96% were susceptible to cefepime (MIC < or = 16 mg/L), respectively, when tested with an inoculum of 10(4) cfu. However, with an inoculum of 10(7) cfu, 98% and 100% of strains were resistant, respectively. Furthermore, the bactericidal activity of cefepime against ceftazidime-resistant isolates was also inoculum-dependent. In time-kill studies, bactericidal action was obtained only at the lowest concentration of organisms (10(4) cfu/mL). beta-Lactamase extracted from an isolate of P. aeruginosa that demonstrated an inoculum effect had a lower affinity for cefepime than for ceftazidime. Overall, cefepime proved to be more resistant to hydrolysis by the beta-lactamase. However, differences in kinetics of the beta-lactamase against cefepime or ceftazidime do not appear to be of consequence in determining susceptibility of P. aeruginosa and Enterobacter spp. at high bacterial densities, since most strains with chromosomally-mediated beta-lactamase are highly resistant.

In vitro activity of RP 59500 (quinupristin/dalfopristin) against antibiotic-resistant strains of Streptococcus pneumoniae and enterococci.

The activity of RP 59500 (quinupristin/dalfopristin) was evaluated in vitro against antibiotic-resistant strains of Streptococcus pneumoniae (N = 15) and Enterococcus spp. (N = 43). By broth dilution MIC tests RP 59500 was highly active against penicillin-resistant S. pneumoniae and vancomycin-resistant Enterococcus faecium, but showed poor activity against E. faecalis. In time-kill studies the drug was rapidly bactericidal against S. pneumoniae but failed to kill most enterococci, even in the presence of gentamicin or human serum.

Assessing diagnostic criteria for active infective endocarditis.

A study was performed to describe agreement among experts on their classification of patients, in the absence of information concerning risk factors, as to the presence of infective endocarditis (IE). The study also assessed the clinical characteristics that enabled the experts to determine that a patient had IE. All patients with a discharge diagnosis of IE were identified prospectively from 54 hospitals in the Delaware Valley over a 3-year period. Patients were part of a case-control study of risk factors for IE. Three infectious disease experts independently reviewed abstracted hospital records and classified each of 151 eligible patients as a definite, probable or possible case, or a probable noncase, both based on clinical judgement and using a modified standard definition. Experts were more likely to classify a patient as a definite case of IE on the basis of clinical judgement than by using the modified standard definition. Agreement between reviewers was 92 to 95% when they were distinguishing only probable non-cases from others. Agreement between reviewers on specific categories was lower (40 to 58%). The number of positive blood cultures was a strong predictor of a patient's being classified as a case, as was the type of infecting organism. It is concluded that experts are willing to make a definitive diagnosis of IE on the basis of blood culture information alone. Further supporting evidence, such as the presence of vegetation on an echocardiogram, is needed when blood culture results are ambiguous.

Antibiotic treatment of experimental endocarditis due to vancomycin- and ampicillin-resistant Enterococcus faecium.

We compared ciprofloxacin, rifampin, and gentamicin treatments, alone and in combination, for 5 days in the therapy of experimental aortic valve endocarditis in rats caused by a clinical isolate of vancomycin-resistant Enterococcus faecium. The MICs and MBCs of vancomycin, ciprofloxacin, rifampin, and gentamicin were 250 and > 1,000, 3.1 and 6.3, 0.098 and 1.6, and 12.5 and > 50 micrograms/ml, respectively. Infected rats were sacrificed after completing 5 days of therapy. Additional rats within each treatment group were followed for 5 days beyond the last dose of antibiotic therapy. Although survivals in the different groups were not significantly different after 5 days of therapy, survival was significantly better 5 days beyond the last dose of antibiotic therapy in rats treated with rifampin-containing regimens. The combination of ciprofloxacin and gentamicin was bactericidal in vitro and in vegetations from rats with enterococcal endocarditis. Rifampin alone was similarly bactericidal in vivo, but it was not significantly better than rifampin in combination with other antibiotics. Subpopulations resistant to rifampin, but not ciprofloxacin, were detected in the inoculum and in most vegetations during therapy. However, the combination of ciprofloxacin plus both gentamicin and rifampin reduced both the rifampin-susceptible and -resistant population in vegetations of 9 of 10 animals below the level of detection after 5 days of therapy. Nevertheless, a residual enterococcal population apparently remained in numbers of < 2 log10 CFU/g after 5 days of therapy, which resulted in relapse. Perhaps a longer course of therapy would have eliminated this residual population and improved efficacy.