cefepime and Endocarditis--Bacterial

A variety of microorganisms can cause infective endocarditis (IE) in patients with native valves. Staphylococci and streptococci are most common in community-acquired IE; staphylococci are most common in nosocomial IE. Microbiology of prosthetic valve endocarditis (PVE) depends on timing. Early-onset PVE (ie, 60 days or fewer postsurgery) typically is nosocomial, with Staphylococcus aureus infection being most common. Intermediate-onset PVE (ie, 60 to 365 days postsurgery) typically involves a mix of nosocomial and non-nosocomial organisms. PVE that develops more than 1 year after surgery has microbiology similar to that of native valve endocarditis. Fever is the most common symptom; others include dyspnea, pleuritic pain, anorexia, and myalgias. The Modified Duke Criteria is the standard for diagnosis, with blood cultures being the most important test. If patients are in stable condition, three sets of blood cultures should be obtained more than 6 hours apart and from separate sites before starting antibiotics. Echocardiography aids in diagnosis and can identify conditions best managed with surgery. For empiric therapy for native valve IE, most patients should receive vancomycin. For PVE, vancomycin and gentamicin should be prescribed, plus cefepime or an antipseudomonal carbapenem. Treatment typically continues for 6 weeks after blood culture results are negative.

Topics: Anti-Bacterial Agents; Blood Culture; Carbapenems; Cefepime; Cephalosporins; Cross Infection; Echocardiography; Endocarditis; Endocarditis, Bacterial; Gentamicins; Heart Valve Prosthesis; Humans; Prosthesis-Related Infections; Staphylococcal Infections; Staphylococcus aureus; Streptococcal Infections; Vancomycin

Topics: Administration, Cutaneous; Adult; Cefepime; Cerebral Infarction; Dermatitis, Atopic; Echocardiography; Endocarditis, Bacterial; Female; Glucocorticoids; Heart Valve Prosthesis Implantation; Humans; Magnetic Resonance Imaging; Skin; Staphylococcal Infections; Staphylococcus aureus; Treatment Outcome

Topics: Adult; Anti-Bacterial Agents; Bacteremia; Cefepime; Cephalosporins; Daptomycin; Endocarditis, Bacterial; Humans; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Middle Aged; Staphylococcal Infections; Vancomycin

Topics: Aged; Aneurysm, False; Anti-Bacterial Agents; Aortic Valve; Aortic Valve Insufficiency; Aortic Valve Stenosis; Cefepime; Cephalosporins; Drug Therapy, Combination; Echocardiography; Echocardiography, Doppler, Color; Echocardiography, Transesophageal; Endocarditis, Bacterial; Enterococcus; Gram-Positive Bacterial Infections; Heart Failure; Heart Valve Prosthesis Implantation; Humans; Male; Mitral Valve; Mitral Valve Insufficiency; Tricuspid Valve Insufficiency; Vancomycin

This paper discusses a 26-year-old woman with end-stage renal disease on hemodialysis and Acinetobacter calcoaceticus-baumannii complex endocarditis. The patient had an indwelling right internal jugular catheter that was probably the nidus of infection. Transthoracic echocardiogram revealed an atypical presentation of the endocarditis as a large intracardiac mass, measuring in centimeters and occupying more than 50% of the right atrial cavity. The mass was attached to the lateral wall of the right atrium without valvular involvement. The patient was treated with prompt removal of the indwelling catheter, intravenous antibiotics, and surgical resection of the mass with an uneventful recovery. A literature search for cases of "Acinetobacter endocarditis" reveals this as the first case reported of Acinetobacter endocarditis presenting in this manner.

Topics: Acinetobacter Infections; Adult; Anti-Bacterial Agents; Catheters, Indwelling; Cefepime; Cephalosporins; Diagnosis, Differential; Endocarditis, Bacterial; Female; Heart Atria; Humans; Kidney Failure, Chronic; Ofloxacin; Ultrasonography; Vancomycin

Reduced susceptibility to daptomycin has been reported in patients with infections due to methicillin-resistant Staphylococcus aureus (MRSA). Although infections with daptomycin-nonsusceptible (DNS) MRSA are infrequent, optimal therapy of these strains has not been determined. We investigated the killing effects of novel antibiotic combinations with daptomycin (DAP) against two clinical DNS MRSA isolates (SA-684 and R6003) in a 72-h in vitro pharmacokinetic/pharmacodynamic (PK/PD) model with simulated endocardial vegetations (SEV). Simulated regimens included DAP at 6 mg/kg every 24 h (q24h) alone or in combination with trimethoprim-sulfamethoxazole (TMP/SMX) at 160/800 mg q12h, linezolid (LIN) at 600 mg q12h, cefepime (CEF) at 2 g q12h, and nafcillin (NAF) at 4 g q4h. Bactericidal activity was defined as a ≥3-log(10) CFU/g kill. Differences in CFU/g were evaluated between 4 and 72 h by analysis of variance with the Bonferroni post hoc test. DAP MICs were 4 and 2 mg/liter for SA-684 and R6003, respectively. In the PK/PD model, DAP alone was slowly bactericidal, achieving a 3-log(10) kill at 24 and 50 h for SA-684 and R6003, respectively. Against SA-684, DAP plus TMP/SMX, CEF, LIN, or NAF was bactericidal at 4, 4, 8, and 8 h, respectively, and maintained this activity for the 72-h study duration. DAP plus TMP/SMX or CEF exhibited superior killing than DAP alone against SA-684 between 4 and 72 h, and overall this was significant (P < 0.05). Against R6003, DAP plus TMP/SMX was bactericidal (8 h) and superior to DAP alone between 8 and 72 h (P < 0.001). The unique combination of DAP plus TMP/SMX was the most effective and rapidly bactericidal regimen against the two isolates tested and may provide a clinical option to treat DNS S. aureus infections.

Topics: Acetamides; Anti-Infective Agents; Cefepime; Cephalosporins; Daptomycin; Drug Combinations; Endocarditis, Bacterial; Linezolid; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Nafcillin; Oxazolidinones; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Aged; Anti-Bacterial Agents; Aortic Valve; Bacteremia; Cefepime; Cephalosporins; Echocardiography, Transesophageal; Endocarditis, Bacterial; Escherichia coli; Escherichia coli Infections; Follow-Up Studies; Humans; Male; Microbial Sensitivity Tests; Time Factors; Treatment Outcome

Pseudomonas aeruginosa is a rare cause of infective endocarditis. The case of community-acquired P. aeruginosa infective endocarditis reported here is the first described in the literature to present as bacterial meningitis. Furthermore, new risk factors for P. aeruginosa infective endocarditis, including mitral annular calcification and re-use of insulin syringes, are proposed. Treatment of P. aeruginosa infective endocarditis complicated by bacterial meningitis is discussed.

Topics: Acyclovir; Ampicillin; Calcification, Physiologic; Cefepime; Cephalosporins; Community-Acquired Infections; Diagnosis, Differential; Echocardiography, Transesophageal; Endocarditis, Bacterial; Female; Gentamicins; Humans; Meningitis, Bacterial; Middle Aged; Pseudomonas aeruginosa; Pseudomonas Infections; Risk Factors; Vancomycin

The purpose of this experimental study was first to compare the in vivo intrinsic activity of imipenem and cefepime administered as a continuous infusion and to determine their lowest effective serum steady-state concentration (LESSC). Secondly, we studied the effect of combining therapy with tobramycin.. In a Pseudomonas aeruginosa (ATCC 27853) rabbit endocarditis model, beta-lactam antibiotics were administered by continuous infusion over a 24 h treatment period at different doses until the LESSC was reached, i.e. able to achieve a 2-log drop of cfu/g of vegetations versus untreated animals. The effect of adding tobramycin (3 mg/kg once daily) was then studied.. The LESSC was between 3 x and 4 x MIC of cefepime for P. aeruginosa and about 0.2 5x MIC of imipenem. Combination of tobramycin with each of the two beta-lactams did not result in any further significant killing.. The optimal Css/MIC ratio might differ from one molecule to another. The LESSC of imipenem is lower than that of cefepime, giving a better intrinsic activity in vivo, despite a higher MIC in vitro.

Topics: Animals; Anti-Bacterial Agents; Cefepime; Cephalosporins; Disease Models, Animal; Drug Therapy, Combination; Endocarditis, Bacterial; Female; Humans; Imipenem; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections; Rabbits; Tobramycin

Topics: Aged; Amikacin; Aorta; Aortic Aneurysm; Aortic Valve; Bacteremia; Cefepime; Cephalosporins; Drug Therapy, Combination; Endocarditis, Bacterial; Humans; Male; Neisseria elongata; Neisseriaceae Infections; Species Specificity; Ultrasonography

Quinupristin-dalfopristin (Q-D) is an injectable streptogramin active against most gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA). In experimental endocarditis, however, Q-D was less efficacious against MRSA isolates constitutively resistant to macrolide-lincosamide-streptogram B (C-MLS(B)) than against MLS(B)-susceptible isolates. To circumvent this problem, we used the checkerboard method to screen drug combinations that would increase the efficacy of Q-D against such bacteria. beta-Lactams consistently exhibited additive or synergistic activity with Q-D. Glycopeptides, quinolones, and aminoglycosides were indifferent. No drugs were antagonistic. The positive Q-D-beta-lactam interaction was independent of MLS(B) or beta-lactam resistance. Moreover, addition of Q-D at one-fourth the MIC to flucloxacillin-containing plates decreased the flucloxacillin MIC for MRSA from 500 to 1,000 mg/liter to 30 to 60 mg/liter. Yet, Q-D-beta-lactam combinations were not synergistic in bactericidal tests. Rats with aortic vegetations were infected with two C-MLS(B)-resistant MRSA isolates (isolates AW7 and P8) and were treated for 3 or 5 days with drug dosages simulating the following treatments in humans: (i) Q-D at 7 mg/kg two times a day (b.i.d.) (a relatively low dosage purposely used to help detect positive drug interactions), (ii) cefamandole at constant levels in serum of 30 mg/liter, (iii) cefepime at 2 g b.i.d., (iv) Q-D combined with either cefamandole or cefepime. Any of the drugs used alone resulted in treatment failure. In contrast, Q-D plus either cefamandole or cefepime significantly decreased valve infection compared to the levels of infection for both untreated controls and those that received monotherapy (P < 0.05). Importantly, Q-D prevented the growth of highly beta-lactam-resistant MRSA in vivo. The mechanism of this beneficial drug interaction is unknown. However, Q-D-beta-lactam combinations might be useful for the treatment of complicated infections caused by multiple organisms, including MRSA.

Topics: Animals; Anti-Bacterial Agents; Cefamandole; Cefepime; Cephalosporins; Disease Models, Animal; Drug Resistance, Microbial; Drug Resistance, Multiple; Drug Therapy, Combination; Endocarditis, Bacterial; Humans; Lincosamides; Macrolides; Microbial Sensitivity Tests; Rats; Staphylococcal Infections; Staphylococcus aureus; Time Factors; Virginiamycin

The efficacy of cefepime, a new broad-spectrum cephalosporin, was compared with those of cefpirome, ceftazidime, vancomycin, imipenem-cilastatin and penicillin G in a rat model of endocarditis caused by a methicillin-susceptible strain of Staphylococcus aureus. Rats were infected intravenously with approximately 10(5) cfu of a penicillin-resistant strain of S. aureus 24 h after placement of a catheter into the left ventricle of the heart via the carotid artery. Efficacy was evaluated by comparing bacterial counts in the cardiac vegetations of treated rats with those of untreated controls. Rats treated with cefepime, cefpirome, ceftazidime, imipenem-cilastatin and vancomycin showed a reduction in the number of bacteria recovered from cardiac vegetations compared with infected control animals; penicillin G was ineffective in this respect. Serum concentrations of the study antimicrobials were determined at selected times following the administration of a single subcutaneous dose. The pharmacokinetic parameters of the cephalosporins were similar in these animals. This study shows that cefepime may be of value in the treatment of staphylococcal endocarditis.

Topics: Animals; Anti-Bacterial Agents; Cefepime; Cephalosporins; Endocarditis, Bacterial; Half-Life; Heart; Male; Microbial Sensitivity Tests; Rats; Rats, Sprague-Dawley; Staphylococcal Infections; Staphylococcus aureus

The efficacy of ciprofloxacin, BMY-28142, and ceftazidime was compared in vitro and in experimental left-sided endocarditis due to Pseudomonas aeruginosa in the rat. The dose, dosing interval, and duration of therapy were varied, and the resulting antibiotic levels in serum and vegetations were correlated with bacterial clearance from vegetations. These studies demonstrated that beta-lactams such as BMY exhibited a slow rate of bactericidal action and had no postantibiotic effect against P. aeruginosa in vitro or in vivo. As a consequence, BMY had to be given in multiple doses at relatively short intervals during which concentrations of antibiotics in vegetations were continuously in excess of the MBC for the pathogen. The earlier onset of rapid bactericidal action and the prolonged postantibiotic effect of ciprofloxacin (demonstrated in vivo and in vitro) were, in all likelihood, the factors that allowed the successful use of fewer doses of this antimicrobial agent at relatively longer dosing intervals.

Topics: Animals; Cefepime; Ceftazidime; Cephalosporins; Ciprofloxacin; Drug Therapy, Combination; Endocarditis, Bacterial; Gentamicins; Pseudomonas aeruginosa; Pseudomonas Infections; Quinolines; Rats; Rats, Inbred Strains; Time Factors