ABSTRACT
The effect of high N-acetylcysteine (NAC) concentrations (10 and 50 mM) on antibiotic activity against 40 strains of respiratory pathogens was investigated. NAC compromised the activity of carbapenems (of mostly imipenem and, to lesser extents, meropenem and ertapenem) in a dose-dependent fashion. We demonstrated chemical instability of carbapenems in the presence of NAC. With other antibiotics, 10 mM NAC had no major effects, while 50 mM NAC sporadically decreased (ceftriaxone and aminoglycosides) or increased (penicillins) antibiotic activity.
Subject(s)
Acetylcysteine/pharmacology , Anti-Bacterial Agents/pharmacology , Imipenem/pharmacology , Thienamycins/pharmacology , beta-Lactams/pharmacology , Aminoglycosides/antagonists & inhibitors , Aminoglycosides/pharmacology , Ceftriaxone/antagonists & inhibitors , Ceftriaxone/pharmacology , Drug Combinations , Drug Interactions , Enterobacter cloacae/drug effects , Enterobacter cloacae/growth & development , Enterobacter cloacae/isolation & purification , Ertapenem , Escherichia coli/drug effects , Escherichia coli/growth & development , Escherichia coli/isolation & purification , Humans , Imipenem/antagonists & inhibitors , Klebsiella pneumoniae/drug effects , Klebsiella pneumoniae/growth & development , Klebsiella pneumoniae/isolation & purification , Meropenem , Microbial Sensitivity Tests , Penicillins/agonists , Penicillins/pharmacology , Pseudomonas aeruginosa/drug effects , Pseudomonas aeruginosa/growth & development , Pseudomonas aeruginosa/isolation & purification , Respiratory Tract Infections/microbiology , Staphylococcus aureus/drug effects , Staphylococcus aureus/growth & development , Staphylococcus aureus/isolation & purification , Streptococcus pneumoniae/drug effects , Streptococcus pneumoniae/growth & development , Streptococcus pneumoniae/isolation & purification , Streptococcus pyogenes/drug effects , Streptococcus pyogenes/growth & development , Streptococcus pyogenes/isolation & purification , Thienamycins/antagonists & inhibitors , beta-Lactams/antagonists & inhibitorsABSTRACT
The preventive effect of betamipron (N-benzoyl-3-propionic acid: BP) on the renal uptake and nephrotoxicity of carbapenems (panipenem and imipenem) was studied in rabbits. Panipenem, a new carbapenem antibiotic, induced nephrotoxicity at a dose of 200 mg/kg, i.v., but this was less severe than that caused by a single dose of imipenem or cephaloridine. Along with the significant reduction of nephrotoxicity, the uptake of these carbapenems in the renal cortex was remarkably inhibited by simultaneous treatment with BP (200 mg/kg, i.v.). These results suggest that BP reduces the nephrotoxicity of carbapenems through inhibiting the active transport of carbapenems in the renal cortex. Because of the low toxicity of BP (LD50 in the rat, more than 3,000 mg/kg, i.v.), it was concluded that BP might be a good candidate for reducing the nephrotoxicity induced by panipenem or imipenem.
Subject(s)
Alanine/analogs & derivatives , Carbapenems/antagonists & inhibitors , Carbapenems/metabolism , Kidney Cortex/metabolism , Kidney Diseases/prevention & control , Alanine/pharmacokinetics , Alanine/pharmacology , Alanine/therapeutic use , Animals , Carbapenems/toxicity , Glycosuria, Renal/chemically induced , Imipenem/antagonists & inhibitors , Imipenem/pharmacokinetics , Imipenem/toxicity , In Vitro Techniques , Kidney Cortex/drug effects , Kidney Diseases/chemically induced , Kidney Diseases/urine , Male , Necrosis/chemically induced , Necrosis/pathology , Proteinuria/chemically induced , Rabbits , Thienamycins/antagonists & inhibitors , Thienamycins/pharmacokinetics , Thienamycins/toxicityABSTRACT
The activity of meropenem was similar to that of imipenem against 88 clinical isolates of Bacteroides spp., including 28 non-fragilis strains. Four of the isolates were able to hydrolyse cephamycins or penems. Investigation of beta-lactamases from these strains and 10 laboratory stock culture Bacteroides showed that meropenem and imipenem were degraded at a similar rate by cell-free preparations of these enzymes. Some of these strains were able to completely hydrolyse the carbapenems within 2 h. Despite this rapid hydrolysis, MICs of meropenem and imipenem for some of the strains remained within the susceptible range as judged by agar dilution titration.
Subject(s)
Bacteroides/drug effects , Thienamycins/metabolism , beta-Lactamases/metabolism , Anti-Bacterial Agents/pharmacology , Bacteroides/enzymology , Hydrolysis , Imipenem/metabolism , Imipenem/pharmacology , Meropenem , Microbial Sensitivity Tests , Species Specificity , Thienamycins/antagonists & inhibitors , Thienamycins/pharmacologyABSTRACT
Imipenem (formerly N-formimidoyl thienamycin) and ceftazidime were investigated for their postantibiotic effect on Pseudomonas aeruginosa. Four strains of P. aeruginosa in the logarithmic phase of growth were exposed for 1 and 2 h to concentrations of antibiotics achievable in human serum. Recovery periods of test cultures were evaluated after dilution or addition of beta-lactamase. A consistent postantibiotic effect against all strains was obtained with imipenem but not with ceftazidime. Although ceftazidime did not have a postantibiotic effect, it did suppress the growth of the organisms at concentrations equivalent to one-third of the MIC. The clinical implications of these effects need further evaluation.
Subject(s)
Anti-Bacterial Agents/pharmacology , Ceftazidime/pharmacology , Pseudomonas aeruginosa/growth & development , Thienamycins/pharmacology , Amikacin/pharmacology , Anti-Bacterial Agents/antagonists & inhibitors , Ceftazidime/antagonists & inhibitors , Imipenem , Microbial Sensitivity Tests , Moxalactam/pharmacology , Pseudomonas aeruginosa/drug effects , Thienamycins/antagonists & inhibitors , Time Factors , beta-Lactamases/pharmacologyABSTRACT
Chloramphenicol combined with cefotaxime, moxalactam, cefoperazone, aztreonam, or imipenem was tested in vitro against clinical isolates of Klebsiella pneumoniae. By time-kill cultures (killing curves), chloramphenicol interfered with activity of all five beta-lactams. When chloramphenicol was added before the beta-lactams, the action of cefotaxime, moxalactam, or cefoperazone against all isolates was antagonized at all times tested. The action of aztreonam was antagonized against four of six isolates. With imipenem, antagonism occurred against half of the isolates at some time during 24 h when chloramphenicol was added simultaneously, provided that a sufficient inoculum of K. pneumoniae was employed. Generally, less antagonism resulted when chloramphenicol was added after the cephalosporins. Interference of bactericidal activity of three new cephalosporins by chloramphenicol has potential clinical relevance to the therapy of gram-negative bacillary meningitis. The lesser antagonism of aztreonam and imipenem by chloramphenicol is of uncertain clinical relevance but indicates that this in vitro phenomenon may apply to a wide range of beta-lactam antibiotics.
