Phenomenon of resistance to Augmentin associated with sensitivity to ampicillin: occurrence and explanation.

Ampicillin was found to be some tenfold more active than amoxycillin against Enterobacter cloacae. This finding explains the observation that some Ent cloacae strains are sensitive to ampicillin in the disc test but resistant to Augmentin. Ampicillin was also found to be more active than amoxycillin against Citrobacter freundii and Serratia marcescens. In view of these findings, the practice of using ampicillin discs to predict sensitivity to amoxycillin should be reconsidered. The use of both ampicillin and amoxycillin discs is appropriate if errors are to be avoided.

The in vitro activity of the newer beta-lactam antibiotics against 124 strains of gram-negative bacilli.

The MIC values of 99 isolates of Enterobacteriaceae to 11 of the newer beta-lactam antibiotics, and 25 isolates of Pseudomonas aeruginosa to 9 of these drugs were compared with representatives of the established beta-lactam antibiotics and gentamicin. The MIC values for the newer agents were significantly lower in comparison with the older reference compounds. The potential clinical use of these newer antibiotics is discussed.

In vitro activity of six antibiotics against multiresistant staphylococci and other gram-positive cocci.

Sixty-two strains of Staphylococcus aureus and coagulase-negative staphylococci, 21 Streptococcus faecalis and 17 other strains of streptococci isolated from cases of endocarditis were tested for sensitivity against rifampicin, teicoplanin, vancomycin, fusidic acid, erythromycin and novobiocin. Only rifampicin, novobiocin and teicoplanin were found to be active against the great majority of these strains. The microbial properties of these antibiotics suggest the necessity of combinations for effective therapy. The combinations rifampicin + novobiocin and rifampicin + teicoplanin were additive and suppressed the emergence of resistant mutants. Thus according to in vitro tests, either of these two combinations would be suitable for prophylactic use in high-risk patients, especially those scheduled to receive prosthetic implants.

In vitro activity of combinations of antibiotics against Staphylococcus aureus resistant to gentamicin and methicillin.

Twenty clinical isolates of Staphylococcus aureus, resistant to both gentamicin and methicillin, were tested in vitro for sensitivity to rifampicin, novobiocin, fusidic acid, vancomycin, teicoplanin and an extended range of aminoglycosides. Rifampicin was the most active compound tested, having an MIC of less than 0.02 mg/l. All the strains were inhibited by 1 mg/l of novobiocin, vancomycin and teicoplanin, and only one strain was resistant to fusidic acid. 50% of the strains were inhibited by less than 1 mg/l of amikacin and netilmicin, but other aminoglycosides were of poor activity. Resistant mutants were selected when strains were grown in the presence of rifampicin, novobiocin or fusidic acid alone, but this did not occur when rifampicin was combined with either novobiocin or vancomycin. Pharmacokinetic and other considerations suggest that a combination of rifampicin and novobiocin deserves further assessment for the treatment of infections caused by this type of organism.

Use of rifampin for the treatment of urinary tract infections.

The pharmacokinetic and microbiologic properties of rifampin are such that the antibiotic appears suitable for the treatment of urinary tract infections. However, its use alone for this indication is associated with an unacceptably high rate (approximately 30%) of acquisition of high-level resistance during therapy-an event that results in the failure of treatment. The combination of rifampin with another suitable antibiotic prevents this emergence of resistance. In vitro, pharmacokinetic, epidemiologic, and clinical studies with a combination of rifampin and trimethoprim (300 mg of rifampin: 80 mg of trimethoprim) both in England and in other countries have shown that this combination is effective and safe for the treatment of recurrent urinary tract infections. Provided that careful laboratory controls are used, the combination of rifampin and trimethoprim is a useful addition to the list of antibiotics available for the treatment of this condition.

Stability of aminoglycoside resistance in vitro in gentamicin-resistant Staphylococcus aureus.

Stability of aminoglycoside resistance has been investigated in 20 strains of Staphylococcus aureus resistant to gentamicin (16 strains were also resistant to methicillin). In view of previous reports that incubation at elevated temperatures can hasten the loss of unstable antibiotic resistance, we passaged strains daily in a liquid medium for 24 days at 43 degrees C. The nine strains which were resistant to neomycin kept their aminoglycoside resistance virtually intact, whereas most of the other 11 strains (sensitive to neomycin) lost almost all their resistance to gentamicin and kanamycin after 5 days. It thus appears that the stability of aminoglycoside resistances in Staph. aureus is closely linked to the resistance of the strains to neomycin. This finding has important possible consequences in terms of the advisability of the clinical usage of preparations containing neomycin or framycetin for topical application and bowel sterilization.

Activity of rifampicin against staphylococci, with special reference to multiresistant strains.

Antibiotic-sensitive and multiply-resistant isolates of Staphylococcus aureus and Staph. epidermidis were all sensitive to rifampicin (MIC less than or equal to 0.015) mg/l) and to novobiocin, vancomycin and teicoplanin (MICs less than 1 mg/l). No tolerance was observed. Resistance sometimes developed in bactericidal tests on rifampicin or novobiocin alone, but not with vancomycin or teicoplanin, or with combinations. The implications of these findings are discussed in the context of serious infections with staphylococci, especially those resistant to beta-lactams and aminoglycosides.

Intravenous co-trimoxazole therapy in serious infections.

The intravenous therapy with co-trimoxazole was used to control serious sepsis in 15 patients in the intensive care unit of a large metropolitan hospital. Co-trimoxazole was found to be a safe, effective, and eminently satisfactory alternative to the present vogue treatments of serious, bacteriologically undiagnosed infections.