Clinical evaluation of moxalactam: evidence of decreased efficacy in gram-positive aerobic infections

Salzer, William; Pegram, P. Samuel; McCall, Charles E.

doi:10.1128/aac.23.4.565

Cited by 33 publications

(5 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This lack of resistance may be due in part to the infrequent use of chloramphenicol as treatment of bacterial infections. However, failure of chloramphenicol treatment for a patient with meningitis and ventriculitis caused by B. fragilis was reported [103].…”

Section: Chloramphenicolmentioning

confidence: 99%

Antimicrobial Resistance in Anaerobes

Rasmussen

Bush

Tally

1997

Clinical Infectious Diseases

160

View full text Add to dashboard Cite

The development of antibiotic resistance in anaerobic bacteria has a tremendous impact on the selection of antimicrobial agents for empirical therapy. Susceptibility studies have documented the emergence of antimicrobial resistance and indicate distinct differences in resistance patterns related to individual hospitals, geographic regions, and antibiotic-prescribing regimens. Resistance to beta-lactam drugs, clindamycin, tetracyclines, and 5-nitroimidazoles (metronidazole) has been observed. The prime mechanism for resistance to beta-lactam agents is the production of beta-lactamases. Resistance to clindamycin is mediated by modification of the ribosome. Tetracycline resistance is mediated by both tetracycline efflux and ribosomal protection. 5-Nitroimidazole resistance appears to be caused by a combination of decreased antibiotic uptake and decreased nitroreductase activity. The level of chloramphenicol susceptibility remains quite high, whereas uniform resistance to aminoglycosides and quinolones is observed. Understanding the mechanisms of resistance is critical for both informed selection of antimicrobial therapy and the design of new antimicrobial agents.

show abstract

Section: Chloramphenicolmentioning

confidence: 99%

Antimicrobial Resistance in Anaerobes

Rasmussen

Bush

Tally

1997

Clinical Infectious Diseases

160

View full text Add to dashboard Cite

show abstract

“…In marked contrast to previously published series, scattered reports of therapeutic failures have begun to appear in the medical literature (2,5,8,12). With obtained from various manufacturers and solubilized according to the manufacturers' instructions.…”

Section: Manuscript In Preparation)mentioning

confidence: 57%

Examination of gram-negative bacilli from meningitis patients who failed or relapsed on moxalactam therapy

Eng¹,

Cherubin²,

Smith³

et al. 1984

Antimicrob Agents Chemother

View full text Add to dashboard Cite

One Salmonella and four Escherichia coli isolates from patients with bacterial meningitis who had responded slowly, relapsed, or failed to respond to monotherapy with moxalactam were examined. For purposes of comparison, an E. coli isolate from one patient who had responded promptly to therapy was also studied. On testing, moxalactam had higher MICs and MBCs (two to four times) than cefotaxime or ceftriaxone for all isolates; the rates of killing of the isolates were dependent on the antibiotic concentrations used. At comparable multiples of the MIC, these isolates were generally killed more slowly by moxalactam than by cefotaxime or ceftriaxone. In addition, a reduction of 3 in the logarithm of the number of CFU per milliliter could be attained at far lower concentrations with cefotaxime or ceftriaxone than with moxalactam. The degree of concentrationrelated killing of bacteria produced by the beta-lactams appeared to correlate with the clinical responses of the patients. Furthermore, real differences appeared to exist among the third-generation cephalosporins, which were not evident by the MIC and MBC points alone but were evident in the concentration-related killing curves. Determination of a reduction of 3 in the logarithm of the number of CFU per milliliter after a 6-h incubation is suggested as the criterion for the screening of antibiotics for the therapy of gram-negative bacillary meningitis.Soon after their introduction, the newer third-generation cephalosporins were generally accepted as potential antibacterial agents of choice for the therapy of gram-negative bacillary meningitis (1,4,11). A recent survey of infectious disease consultants in the United States showed that these antibiotics were indeed being used for the treatment of meningitis cases involving a wide range of bacterial pathogens (C. E. Cherubin, manuscript in preparation).In marked contrast to previously published series, scattered reports of therapeutic failures have begun to appear in the medical literature (2,5,8,12 Susceptibility testing. The CSF isolates were tested for susceptibility to antibiotics in three ways. First, the isolates were tested by the macro-broth dilution method with an inoculum of 5 x 105 CFU in 1 ml (14). A 0.1-ml portion was subcultured from each tube after an 18-h incubation at 35°C, and the criterion of 99.9% killing was used for the MBC. Second, the method described by Eng et al. (6) was used to ascertain the effect of a large inoculum on the susceptibility results. For this procedure, the organisms were tested by the same macro-broth dilution method but at an inoculum of 5 x 107 CFU/ml. The MIC at the higher inoculum was determined by the highest drug dilution which inhibited turbidity formation in the tube, compared with a control tube containing 1% Formalin and the same inoculum (6). A 100-pl sample from each tube was subcultured after an 18-h incubation at 35°C, and the same criterion of 99.9% killing was used to determine the MBC. Third, the organisms were retested in CSF and in Mueller-Hinton broth by ...

show abstract

“…At least part of the explanation may lie in the inoculum effect on their MICs in the cases of Pseudomonas, Serratia, and Enterobacter species (1). In addition, they may have somewhat less activity in treating staphylococcal and streptococcal infections than older cephalosporins (8). Finally, their somewhat decreased activity against B. fragilis makes them somewhat less attractive in the therapy of intraabdominal abscesses (9).…”

Section: Resultsmentioning

confidence: 99%

Imipenem versus moxalactam in the treatment of serious infections

Eron¹,

Hixon²,

Park³

et al. 1983

Antimicrob Agents Chemother

View full text Add to dashboard Cite

Imipenem (formerly imipemide, N-formimidoyl thienamycin, or MK0787) was compared to moxalactam in a randomized therapeutic trial involving 39 evaluable patients with serious bacterial infections. Of those treated with imipenem, 89% were cured or improved versus 60% for moxalactam (P = 0.06). Although mucocutaneous fungal infections occurred in both groups (25 and 10%, respectively), Streptococcus faecalis superinfection was seen in two patients in the moxalactam group only. Adverse drug reactions occurred with both drugs, although bleeding occurred in three patients treated with moxalactam.Imipenem (formerly imipemide, N-formimidoyl thienamycin, or MK0787) is a novel betalactam antibiotic having desthiocarbapenem as its nucleus. In vitro studies (5) MATERIALS AND METHODSPatients with septicemia, soft tissue, respiratory tract, and urinary tract infections were admitted to a randomized study at The Fairfax Hospital (Falls Church, Va.) comparing moxalactam (2 g intravenously every 8 h) to imipenem (0.5 g intravenously every 6 h) combined with MK0791, a structural analog of imipenem designed to block catabolism of the drug by the brush border of the kidney (6). The method of culturing, laboratory tests for safety, and informed consent have all been described previously (2), with the exception that Mueller-Hinton broth was used for the determination of MICs rather than Trypticase soy broth (BBL Microbiology Systems). Susceptibility to imipenem and moxalactam was initially determined for all isolates by using 10-,ug disks for imipenem and 30-,ug disks for moxalactam. Zones equal to or greater than 16 and 18 mm, respectively, were used to indicate sensitivity. Although we hoped that all isolates would be sensitive to both antibiotics, in several instances in the imipenem group, bacteria were resistant to moxalactam. One patient who had been started on moxalactam was dropped from the study when her P. aeruginosa isolate was shown to be moxalactam resistant. A second patient who developed a rash after a small dose of imipenem was also dropped from the study. Gramstained specimens were examined for the presence of polymorphonuclear leukocytes and homogeneous populations of organisms (except in polymicrobial infections) in an attempt to distinguish pathogens from colonizers identified on cultures.Wound infections showed signs of local inflammation with purulent drainage. Intraabdominal infections consisted of abscesses or cholangitis or both. Respiratory tract infections were diagnosed by the presence of purulent sputum or sinus drainage and radiological evidence of infection of the lung or sinus. Urinary tract infections had colony counts greater than 105 per ml of urine with pyuria noted on urinalysis. Septicemia was defined as the occurrence of two or more positive blood cultures.Cure was defined as the complete resolution of signs of infection accompanied by sterilization of the infected site at the conclusion of therapy. When culture specimens were no longer available, assessment of response was made on clinical g...

show abstract

Clinical evaluation of moxalactam: evidence of decreased efficacy in gram-positive aerobic infections

Cited by 33 publications

References 19 publications

Antimicrobial Resistance in Anaerobes

Antimicrobial Resistance in Anaerobes

Examination of gram-negative bacilli from meningitis patients who failed or relapsed on moxalactam therapy

Imipenem versus moxalactam in the treatment of serious infections

Contact Info

Product

Resources

About