Summary
Methicillin-resistant staphylococci (M-R staphylococci) represent 30% of the staphylococcal strains isolated in our hospital and pose important therapeutic problems. In a preliminaryin vitro checker-board study the bactericidal effect of various cephalosporins (cephalothin, cefamandole, cefotaxime and cefoperazone) in combination with other antibiotics (netilmicin, amikacin, vancomycin and fosfomycin) was studied on ten M-R staphylococcal strains. The combinations of cefoperazone with amikacin, cephalothin with vancomycin and of the four cephalosporins with fosfomycin were synergistic on the ten strains (FBC indexes ⩽0.75). According to the CSF and bone levels achieved by these antibiotics and their bactericidal concentrations in combination, the combination of cefotaxime and fosfomycin was the most interesting, a concentration of ⩽2 mg/l cefotaxime being bactericidal on five homogeneous M-RStaphylococcus aureus when combined with 4 mg/l of fosfomycin. This combination of cefotaxime (25 mg/kg, i.v. infusion over 30 min) and fosfomycin (50 mg/kg, i.v. infusion over three hours) three to four times daily was used to treat 16 patients: three patients with meningitis, six with bone and joint infections and seven with persistent bacteremia. The FBC indexes were ⩽0.625 for the 12 strains studied. All the patients were cured without relapses. The concentrations of cefotaxime, desacetyl cefotaxime and fosfomycin in the CSF during meningitis three hours after the end of the infusion on the second day of treatment were 8.76, 6.82 and 58.0 mg/l, respectively, for patient one and 2.0, 0.53 and 31.0 mg/l, respectively, for patient two. These good results allowed us to treat eight patients with methicillin-sensitive staphylococcal meningitis with this combination. All eight patients were cured.
Zusammenfassung
Methicillin-resistente Staphylokokken (M-R-Staphylokokken) machen 30% der Staphylokokkenisolate unseres Krankenhauses aus, sie verursachen erhebliche Therapieprobleme. In einer vorausgehendenIn vitro-Studie mit Checkerboard-Technik wurde die bakterizide Wirkung verschiedener Cephalosporine (Cephalotin, Cefamandol, Cefotaxim, Cefoperazon) in Kombination mit anderen Antibiotika (Netilmicin, Amikacin, Vancomycin und Fosfomycin) gegen M-R-Staphylokokken geprüft. Die Kombination von Cefoperazon mit Amikacin, von Cephalotin mit Vancomycin und der vier untersuchten Cephalosporine mit Fosfomycin war gegen die zehn geprüften Stämme synergistisch wirksam (FBC-Indices ⩽0,75). Im Hinblick auf die Liquor-und Knochenspiegel und die bakterizide Aktivität der Kombinationen war Cefotaxim mit Fosfomycin am interessantesten. Bakterizide Wirkung gegen fünf homogene M-R-Staphylokokkenstämme wurde bei der Kombination von ⩽2 mg/l Cefotaxim und 4 mg/l Fosfomycin erreicht. Diese Kombination wurde zur Behandlung von 16 Patienten, von denen drei an Meningitis, sechs an Knochen- und Gelenkinfektionen und sieben an persistierender Bakteriämie litten, eingesetzt. Drei- bis viermal täglich wurde Cefotaxim in einer Dosis von 25 mg/kg über 30 min infundiert, Fosfomycin in einer Dosis von 50 mg/kg in dreistündiger i.v.-Infusion appliziert. 12 untersuchte Staphylokokkenstämme wiesen FBC-Indices von ⩽0,625 auf. Alle Patienten wurden ohne Rezidiv geheilt. Bei Meningitis erreichten Cefotaxim, Desacetylcefotaxim und Fosfomycin am zweiten Therapietag drei Stunden nach Infusionsende Liquorkonzentrationen von 8,76, 6,82 und 58,0 mg/l bei Patient eins und 2,0, 0,53 und 31,0 mg/l bei Patient zwei. Nach diesen günstigen Ergebnissen schien es gerechtfertigt, weitere acht Patienten mit Meningitis durch Methicillin-empfindliche Staphylokokken mit der Kombination zu behandeln. Alle acht Patienten wurden geheilt.
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Literature
Soussy, C. J., Duval, J. Evolution de la résistance des staphylocoques aux pénicillines. Sensibilité actuelle deStaphylococcus aureus résistant à la méticilline et autres antibiotiques. In:Vachon, F., Regnier, B. (eds.): Les infections à staphylocoques méticilline résistants. Librairie Arnette, Paris 1984, pp. 7–25.
Acar, J. F., Courvalin, P., Chabbert, Y. A. Methicillin resistant staphylococcemia: bacteriological failure of treatment with cephalosporins. Antimicrob. Agents Chemother. 71 (1970) 280–285.
Klimek, J. J., Marsik, F. J., Bartlett, R. C., Weir, B., Shea, P., Quintiliani, R. Clinical, epidemiologic and bacteriologic observations of an outbreak of methicillin resistantStaphylococcus aureus at a large community hospital. Am. J. Med. 61 (1976) 340–345.
Crossley, K., Loesch, D., Landesman, B., Mead, K., Chern, M., Strate, R. An outbreak of infections caused by strains ofStaphylococcus aureus resistant to methicillin and aminoglycosides. I. Clinical studies. J. Infect. Dis. 139 (1979) 273–279.
Craven, D. E., Kollisch, N. R., Hsieh, C. R., Connolly, M. G., McCabe, W. R. Vancomycin treatment of bacteremia caused by oxacillin-resistantStaphylococcus aureus: comparison withβ-lactam antibiotic treatment of bacteremia caused by oxacillin-sensitiveStaphylococcus aureus. J. Infect. Dis. 147 (1983) 137–143.
Klastersky, J., Coppens, L., Van der Auwera, P., Meunier-Carpentier, F. Vancomycin therapy of oxacillin-resistantStaphylococcus aureus infections. J. Antimicrob. Chemother. 11 (1983) 361–367.
Myers, J. P., Linnemann, C. C. Bacteremia due to methicillin-resistantStaphylococcus aureus. J. Infect. Dis. 145 (1982) 532–536.
Regnier, B., Garaud, J. J., Wolff, M., Laisne, M. J., Rouveix, E., Nkam, M., Vachon, F. La vancomycine seule et en association aux aminosides. In:Vachon, F., Regnier, B. (eds.): Les infections à staphylocoques méticilline résistants. Librairie Arnette, Paris 1984, pp. 119–132.
Sorrell, T. C., Packham, D. R., Shanker, S., Foldes, M., Munro, R. Vancomycin therapy for methicillin-resistantStaphylococcus aureus. Ann. Intern. Med. 97 (1982) 344–350.
Portier, H., Tremeaux, J. C., Chavanet, P., Gouyon, J. B., Duez, J. M., Kazmierczak, A. Treatment of severe staphylococcal infections with cefotaxime and fosfomycin in combination. J. Antimicrob. Chemother. 14 Suppl. B (1984) 277–284.
Le Goffic, F., Martel, A., Moreau, N., Capnau, M. L., Soussy, C. J., Duval, J. 2″O-Phosphorylation of gentamicin components by aStaphylococcus aureus strain carrying a plasmid. Antimicrob. Agents Chemother. 12 (1977) 26–36.
Soussy, C. J., Bouanchaud, D. H., Fouace, J., Dublanchet, A. A gentamicin resistant plasmid inStaphylococcus aureus. Ann. Microbiol. (Institut Pasteur) 126 B (1975) 91–94.
Watanakunakorn, C. Treatment of infections due to methicillin-resistantStaphylococcus aureus. Ann. Intern. Med. 97 (1982) 376–378.
Kazmierczak, A., Portier, H., Chandesris, C., Pothier, P., Labia, R. Determination by high pressure liquid chromatography of cefotaxime and desacetyl-cefotaxime concentrations in cerebrospinal fluid of adults with bacterial meningitis. In:Grassi, C., Pereti, P. (eds.): Current chemotherapy and immunotherapy. American Society for Microbiology, Washington D. C. 1982, pp. 582–583.
Kosmidis, J., Stathakis, Ch., Mantopoulos, K., Pouriezi, T., Papathanassiou, B., Daikos, G. K. Clinical pharmacology of cefotaxime including penetration into bile, sputum, bone and cerebrospinal fluid. J. Antimicrob. Chemother. 6 Suppl. A (1980) 147–151.
Sicilia, T., Estevez, E., Rodriguez, A. Fosfomycin penetration into cerebrospinal fluid of patients with bacterial meningitis. Chemotherapy 27 (1981) 405–413.
Sirot, J., Lopitaux, R., Dumont, C., Rampon, S., Cluzel, R. Diffusion de la fosfomycine dans le tissu osseux chez l'homme. Pathol. Biol. 31 (1983) 522–524.
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Portier, H., Lucht, F., Chavanet, P. et al. Cefotaxime in combination with other antibiotics for the treatment of severe methicillin-resistant staphylococcal infections. Infection 13 (Suppl 1), S123–S128 (1985). https://doi.org/10.1007/BF01644232
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DOI: https://doi.org/10.1007/BF01644232