cilastatin--imipenem-drug-combination and Endocarditis--Bacterial

We herein report the case of 34-year-old woman with acute tricuspid valve infective endocarditis (IE) associated with a ruptured sinus of Valsalva and multiple septic pulmonary emboli. She had no history of medical problems, except for atopic dermatitis (AD). Blood cultures identified methicillin-sensitive Staphylococcus aureus. Despite the administration of two months of antibiotic therapy, the patient experienced recurrent pulmonary emboli and developed heart failure due to a left-to-right shunt, whereas the area of vegetation did not change in size. She subsequently underwent surgery for shunt closure and tricuspid valve replacement. The AD was thought to be the cause of the patient's bacteremia, which consequently resulted in aggressive right-sided IE.

Topics: Adult; Anti-Infective Agents; Cilastatin; Cilastatin, Imipenem Drug Combination; Dermatitis, Atopic; Drug Combinations; Endocarditis, Bacterial; Female; Gentamicins; Heart Failure; Humans; Imipenem; Methicillin-Resistant Staphylococcus aureus; Sinus of Valsalva; Treatment Outcome; Tricuspid Valve

Therapy for endocarditis due to Pseudomonas aeruginosa is complicated by the emergence of resistance during therapy, lack of universally available synergistic antimicrobial agents, and unacceptably high morbidity and mortality rates. The authors report a case of aortic valve endocarditis due to P. aeruginosa in which resistance to piperacillin developed during combined therapy with tobramycin. Bacteriologic cure was obtained with a combination of imipenem/cilastatin and tobramycin. The authors review six other cases of P. aeruginosa endovascular infections treated with imipenem.

Topics: Adult; Anti-Bacterial Agents; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Drug Therapy, Combination; Endocarditis, Bacterial; Humans; Imipenem; Male; Pseudomonas Infections; Tobramycin

To report a case of Pseudomonas aeruginosa endocarditis that was successfully treated with high-dose imipenem/cilastatin and to discuss dosage modification based on individual pharmacokinetic parameters.. Clinical studies, review articles, and relevant laboratory and pharmacokinetic information.. A 27-year-old man with right-sided P. aeruginosa endocarditis was successfully treated with long-term imipenem/cilastatin and tobramycin. The imipenem dose required to achieve therapeutic serum concentrations and cidal activity was 6 g/d. The manufacturer's recommended maximum dose is 4.0 g/d or 50 mg/kg/d. Because of the patient's large apparent volume of distribution, low serum imipenem concentrations, and lack of serum cidal activity, the clinical decision was made to increase the dose to 6 g/d or 54 mg/kg/d. Treatment was tolerated for seven weeks without any adverse effects. The patient remains free of symptoms 24 months after the diagnosis.. Careful and discriminate use of larger-than-recommended doses of imipenem may be indicated in certain clinical situations. Dosage may need to be adjusted to body size in order to obtain optimal serum concentrations and activity.

Topics: Adult; Anti-Bacterial Agents; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Drug Therapy, Combination; Endocarditis, Bacterial; Humans; Imipenem; Male; Pseudomonas Infections; Risk Factors; Tobramycin

Activities of imipenem and vancomycin against methicillin resistant Staphylococcus aureus (MRSA) were compared in vitro and in a rabbit model of aortic valve endocarditis. Against 25 MRSA clinical isolates, imipenem was bacteriostatic (MIC90/MBC90, mg/l 8/32) in vitro while vancomycin was bactericidal (MIC90/MBC90, mg/l 2/4). Rabbit endocarditis was produced with a MRSA isolate against which both drugs were bactericidal. Imipenem-cilastatin had better efficacy than vancomycin by the following criteria, the number of survivors (9/13 vs 7/13), clearance of bacteraemia (9/9 vs 3/7; P = 0.019), sterility of cardiac vegetations (9/9 vs 1/7; P = 0.001) and sterility of distant organs (8/9 vs 2/7; P = 0.035). Thus, imipenem-cilastatin may be a potentially useful alternative agent to vancomycin in the therapy of MRSA endocarditis in the occasional situations when the drug demonstrates in-vitro bactericidal activity against the pathogen. Efficacy against MRSA strains with higher MBCs remains to be proved.

Topics: Animals; Aortic Valve; Cilastatin; Cilastatin, Imipenem Drug Combination; Cyclopropanes; Drug Combinations; Endocarditis, Bacterial; Heart Valve Diseases; Imipenem; Methicillin; Penicillin Resistance; Rabbits; Staphylococcal Infections; Staphylococcus aureus; Thienamycins; Vancomycin