Cardiobacterium hominis - Antimicrobial Therapy

General 

               For many years, penicillin or ampicillin, alone, or in combination with an aminoglycoside, were regarded as the standard treatment for endocarditis due to HACEK organisms. Serum bactericidal titers for C. hominis in patients given penicillin alone have ranged from 1:256 to 1:2560 and the average duration of treatment for cured patients was 37 days with a range of 12-49 days. Twenty-seven [87%] of 31 patients with C. hominis endocarditis, including all 4 patients with prosthetic heart valve involvement, were cured. However, with the emergence of β-lactamase producing strains within the HACEK group of organisms an ad hoc writing group for the American Heart Association now recommends cefotaxime or ceftriaxone as the drugs of choice for treatment of HACEK endocarditis, an approach endorsed by others. The recommended dose of ceftriaxone is 2g once daily intravenously or intramuscularly. The recommended duration of treatment is 3-4 weeks for native valve disease and 6 weeks when a prosthetic valve is involved. A successful outcome has been reported in 11 patients with C. hominis infection of prosthetic valves. Treatment regimens ranged from ampicillin or ceftriaxone alone for 4 weeks, to penicillin or ampicillin, plus gentamicin for almost 6 weeks, and in the only reported case of aortic homograft valve infection, ceftriaxone and gentamicin for 18 days followed by oral amoxicillin.  

               Although third generation cephalosporins have been recommended because of the occurrence of β-lactamase-producing HACEK organisms, this might be questioned for C. hominis infection since ceftriaxone was seemingly ineffective in both cases due to β-lactamase-producing strains. The one patient, whose organism was resistant to cefotaxime in vitro, remained febrile after receiving ceftriaxone for 6 days, and was eventually cured using a combination of vancomycin and rifampicin followed by amoxicillin/clavulanate and rifampicin. The other patient received ampicillin and gentamicin for two weeks, then ceftriaxone (MIC 1.0 μg/ml) 2 g 12 hourly for a further three weeks. At this time she developed a skin rash and was changed to intravenous ciprofloxacin 400 mg 12 hourly, before undergoing aortic valve replacement for progressive heart failure. Although neither patient was proven to have bacteriological failure following the recommended course of ceftriaxone, they illustrate the importance of determining susceptibilities in each case and the occasional need for alternative treatment options. Based on limited data, it would seem reasonable to treat infection due to β-lactamase producing strains of C. hominis with a carbapenem, a β-lactam/β-lactamase-inhibitor combination or a fluoroquinolone. It should, however, be noted that the fluoroquinolones have variable activity e.g. ofloxacin MIC as high as 8.0 μg/ml.  

Alternative Therapy  

               The American Heart Association’s preferred alternative to a third generation cephalosporin is combination treatment with ampicillin and gentamicin, providing the isolate does not produce β-lactamase. The recommended dose of ampicillin is 12g/day intravenously, either continuously or in 6 equally divided doses and that of gentamicin is 1mg/kg intramuscularly or intravenously 8-hourly. Monotherapy with ampicillin is no longer recommended. These recommendations are necessarily made on the basis of scanty published data.  

               There are few precedents for managing infection due to isolates resistant to penicillins or cephalosporins, or for treating patients unable to tolerate these antibiotics. Gentamicin alone for 6 weeks has been reported to be successful. However, the suggested treatments for those with β-lactam allergies are aztreonam or fluoroquinolones or trimethoprim-sulphamethoxazole, provided susceptibility is confirmed. While combination treatment with a β-lactam plus an aminoglycoside is commonly used, there is no evidence that it is superior to monotherapy for C. hominis endocarditis.