Cloxacillin: Class: Antibiotic. Indications: Treatment of Bacterial

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Cloxacillin: Class: Antibiotic. Indications: Treatment of bacterial infections including endocarditis, pneumonia, bone and joint infections, skin and soft-tissue infections, and sepsis that are caused by susceptible strains of penicillinase-producing staphylococci. Note: Exhibits good activity against Staphylococcus aureus; has activity against many streptococci, but is less active than penicillin and is generally not used in clinical practice to treat streptococcal infections. Available dosage form in the hospital: 250MG VIAL, 500MG VIAL, 250MG TABLET. Trade Names: Dosage: -Susceptible infections (manufacturer’s labeling): -Oral: 250-500 mg every 6 hours (maximum adult dose: 6 g/day) -I.M., I.V.: 250-500 mg every 6 hours (maximum adult dose: 6 g/day) Dosing recommendations of World Health Organization unless otherwise noted: -Arthritis (septic), methicillin-sensitive Staphylococcus aureus (MSSA) (unlabeled dosing): I.M., I.V.: 2 g every 6 hours for 2-3 weeks; Note: Oral therapy of 1 g every 6 hours may be used to complete therapy if parenteral therapy is discontinued prior to 2-3 week duration -Endocarditis (MSSA) (unlabeled dosing): I.V.: -Native valve: 2 g every 4 hours for 6 weeks; may give with gentamicin for initial 5 days (Choudri, 2000) -Prosthetic valve: 2 g every 4 hours for 6 weeks; give with gentamicin for 2 weeks and rifampin for 6 weeks (Choudri, 2000) -Uncomplicated endocarditis in I.V. drug users: 2 g every 4 hours for 4 weeks and gentamicin for initial 5 days or 2 g every 4 hours and gentamicin both given for 2 weeks total (Choudri, 2000) -Osteomyelitis (MSSA) (unlabeled dosing): I.M., I.V.: 2 g every 6 hours for 4-6 weeks (preferred) or for a minimum of 14 days, followed by 1 g every 6 hours orally to complete 4-6 weeks of therapy -Pneumonia (MSSA) (unlabeled dosing): I.M., I.V.: 1-2 g every 6 hours for 10-14 days - Renal Impairment : No dosage adjustment necessary. Common side effect: Hypotension, Confusion, fever, lethargy, seizure (high doses and/or renal failure), Pruritus, rash, urticarial, Abdominal pain, black or hairy tongue, diarrhea, flatulence, nausea, oral candidiasis, pseudomembranous colitis, vomiting, Arthralgia, myalgia, sneezing, wheezing. Pregnancy Risk Factor: B .

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Synergistic Activity of Ampicillin and Cloxacillin
144 THE JOURNAL OF ANTIBIOTICS APR. 1969 SYNERGISTIC ACTIVITY OF AMPICILLIN AND CLOXACILLIN PROTECTIVE EFFECT OF CLOXACILLIN ON ENZYMATIC DEGRADATION OF AMPICILLIN BY PENICILLINASE, AND THERAPEUTIC ACTIVITY OF MIXTURES OF AMPICILLIN AND CLOXACILLIN MlNORUNlSHIDA, YASUHIROMlNE Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Osaka, Japan and Shogo Kuwahara Department of Microbiology, Toho University School of Medicine, Tokyo, Japan (Received for publication February 15, 1969) A mixture of ampicillin (aminobenzyl penicillin, AB-PC) and cloxacillin (methylchlorophenylisoxazolyl penicillin, MCI-PC) showed an excellent bacteri- cidal activity even at low concentrations in which either of the penicillins alone did not have any activity against a clinically isolated strain of Escherichia colt, resistant to both of these penicillins. In this case, the microbial degrada- ion of AB-PC, caused by penicillinase (PC-ase), was strongly inhibited in the presence of MCI-PC. The enzymatic hydrolysis of AB-PC by extracellular nd cell-bound PC-ase, obtained from an AB-PC resistant strain of Staphylo- coccus aureus, was also inhibited in the presence of MCI-PC. Against that, t a under comparable conditions, penicillin G (PC-G) was almost completely destroyed by cell-bound PC-ase from this organism. An in vivo synergism was observed when mixtures of AB-PC and MCI-PC were applied for the treatment of mice challenged with a clinically isolated strain of E. coli resistant to both of these penicillins. Similar results were obtained in the treatment of mice experimentally infected with a strain of Staphylococcus aureus, which is highly resistant to AB-PC, but sensitive to MCI-PC. A decrease in the rate of hydrolysis of methicillin (dimethoxyphenyl penicillin, DMP-PC) by staphylococcal penicillinase (PC-ase) was first noted by Rolinson and his co-workers^.
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