Cefotaxime: in vitro activity and tentative interpretive standards for disk susceptibility testing

A paper strip test that detects cefotaxime-resistant variants of gram-negative bacilli was described and compared with a beta-lactamase induction test. Both tests demonstrated a potential for resistance that is not indicated by standard agar dilution and agar diffusion tests.Emergence of bacterial resistance during therapy with third-generation cephalosporins such as cefotaxime has been noted by a number of authors whose findings were recently reviewed by Sanders and Sanders (7). Standard antibioticsusceptibility tests did not reveal the potential for resistance to emerge, and a beta-lactamase induction test (6) has been recommended for this purpose (5). This test detects bacteria that produce the Richmond and Sykes type I chromosomally mediated inducible beta-lactamase (9) which is associated with the emergence of resistance to third-generation cephalosporins (4,5,8,10).We have found that a paper strip test will demonstrate antibiotic-resistant bacterial cells present in a population that appears susceptible when tested by standard methods (4,5,8,9). It has been suggested that these variant cells may survive antibiotic treatment and cause therapy failure (7). We describe the paper strip test and compare it with the beta-lactamase induction test.For the beta-lactamase induction test, Mueller-Hinton agar plates were inoculated with gram-negative bacilli as for disk diffusion susceptibility testing. A 30-,ug cefoxitin disk (Becton Dickinson & Co., Paramus, N.J.) was placed on each plate, and a 30-,ug cefotaxime disk (Biological Laboratories Ltd., Auckland, New Zealand) was placed next to it, separated by a distance equal to the sum of the zones of inhibition for each disk when tested separately. Negative tests showed no change in the zone of inhibition around each cefotaxime disk. Positive tests showed a decreased zone of inhibition, equal to 4 mm or more around the cefotaxime disk adjacent to the cefoxitin disk (Fig. 1) (Fig. 2). * Corresponding author.These colonies were picked off and tested for an increase in cefotaxime resistance.We tested 292 gram-negative bacilli that were recent significant clinical isolates from the microbiology department of our hospital. All were susceptible to cefotaxime at a concentration of 16 pug/ml or less as measured by agar dilution (1). Susceptibilities from agar diffusion tests with 30-,ug cefotaxime disks agreed with agar dilution results (2, 3).Of the 78 isolates of Serratia, Citrobacter, indole-positive Proteus, Enterobacter, and Pseudomonas species, 59 produced colonies within the zone of inhibition next to the paper strip for the heavy inoculum (Table 1). Subsequent tests of these colonies confirmed increased resistance, with MICs of cefotaxime at least four times higher than those of the original inoculum. Still within the clinically susceptible range were 27 isolates that produced colonies with MICs to cefotaxime of 32 ,ug/ml or less. Colonies from 32 isolates had MICs that had increased to, or were greater than, 64 ,ug/ml and were classified as clinically resistant. Of ...

supporting

confidence: 52%

Comparison of a beta-lactamase induction test with a test that detects low-frequency resistance to cefotaxime

Menzies¹,

MacCulloch²

1985

“…Two cases were mixed E. coli-P. mirabilis; one each was E. coli-S. marcescens and Enterobacter agglomerans-Morganella morganii. 9 One case of mixed S. pneumoniae-H. influenzae documented by TTA.…”

Section: Resultsmentioning

confidence: 99%

“…All clinical bacterial isolates from patients in this study were initially tested for susceptibility to cefotaxime with a 30-,ug disk, using a standard disk diffusion technique (2). The interpretive criteria for disk diffusion susceptibility tests were those recently published (9). Additionally, agar dilution minimal inhibitory concentration (MICs) for cefotaxime were determined in Mueller-Hinton agar (BBL Microbiology Systems) for all but three isolates according to techniques defined by the International Collaborative Study (6).…”

Section: Methodsmentioning

confidence: 99%

Clinical evaluation of cefotaxime for therapy of lower respiratory tract infections

Schleupner¹,

Engle²

1982

A clinical trial was designed to evaluate the efficacy and safety of cefotaxime, a new semisynthetic, broad-spectrum cephalosporin, in the therapy of communityand hospital-acquired pneumonias. Thirty-nine males (mean age, 65 years) were treated for 41 episodes of pneumonia. Only five patients did not have a serious underlying disease; 15 had two or more significant disorders. Sixty-six percent of these pneumonias were due to Streptococcus pneumoniae or Haemophilus influenzae. The minimal inhibitory concentrations for all bacterial isolates ranged from 0.008 to 4 ,ug/ml. Peak serum cefotaxime levels during therapy ranged from 12 to 124 ,ug/ml 1 h after a 1-g dose. Satisfactory bacteriological and clinical responses were observed in 85% of the cases. Four episodes of pulmonary superinfections due to cefotaxime-resistant gram-negative bacilli were noted, each in a patient being mechanically ventilated. Pseudomonas was involved in each of these superinfections, and three were fatal. No serious toxicity or adverse reaction to cefotaxime was seen. The results of this study suggest that cefotaxime is an effective and well-tolerated new cephalosporin antimicrobial agent for the therapy of pneumonia due to susceptible organisms.

“…The bacteria most likely to harbor the higher minimal inhibitory concentrations (MICs) for these new ,B-lactams are the nonfermentative bacilli and the serogroup D Streptococcus spp. ; however, a few strains of Enterobacteriaceae may have MICs of 2.0 to 32 ,ug/ml (3,(7)(8)(9). These latter organisms represent a very different population of enteric bacilli only moderately susceptible (MS) to these highly active new drugs.…”

mentioning

confidence: 99%

“…The MIC screening phase and the retesting of strains were performed by dilution susceptibility tests, using methods described previously and published in the latest edition (tentative standard) of the National Committee for Clinical Laboratory Standards (NCCLS) dilution methods (3,14). In the screening tests, two antimicrobial concentrations were used for each drug (1.0 and 32 ±g/ml for cefotaxime, ceftazidime, and moxalactam; 2.0 and 64 ,ug/ml for cefoperazone), and those Enterobacteriaceae isolates ultimately having MICs of .2.0 and c32 F±g/ml were selected for synergy studies at The Clinical Microbiology Institute, Tualatin, Oreg.…”

mentioning

confidence: 99%

Antimicrobial activity of amikacin combinations against Enterobacteriaceae moderately susceptible to third-generation cephalosporins

Jones¹,

Packer²

1982

Self Cite

Enterobacteriaceae strains having elevated minimal inhibitory concentrations (.2.0 to s32 ,ug/ml) of cefoperazone, cefotaxime, ceftazidime, and moxalactam were synergistically inhibited by amikacin combinations (54.1 to 69.6% occurrence). Indifference was rare (8.1% for moxalactam), and true antagonistic interactions were not observed. Strains resistant or susceptible to these new cephalosporins were also synergistically inhibited by the addition of amikacin, reducing resistant cephalosporin minimal inhibitory concentrations to clinically achievable levels.Amikacin has been recognized as the currently available aminoglycoside most refractory to bacterial enzyme inactivation (18). This stability has generally limited the use of amikacin to those clinical bacterial strains resistant to kanamycin, gentamicin, and tobramycin by enzyme plasmid-mediated mechanisms. Similarly, the recently introduced third-generation cephalosporins have substantial stability to bacterial plactamases and a potent antimicrobial activity (2, 3, 6-9, 15, 16). The bacteria most likely to harbor the higher minimal inhibitory concentrations (MICs) for these new ,B-lactams are the nonfermentative bacilli and the serogroup D Streptococcus spp.; however, a few strains of Enterobacteriaceae may have MICs of 2.0 to 32 ,ug/ml (3,(7)(8)(9). These latter organisms represent a very different population of enteric bacilli only moderately susceptible (MS) to these highly active new drugs. Very few Enterobacteriaceae are currently considered resistant (MICs, .64 ,g/ml) to cefoperazone,' cefotaxime, ceftazidime, or moxalactam.To determine the possibility of using antimicrobial combinations to treat infections caused by these MS strains of Enterobacteriaceae (cefoperazone, cefotaxime, ceftazidime, or moxalactam MICs, 2.0 to 32 ,ug/ml), we screened over 6,000 organisms to find strains having elevated MICs as described above. These recent clinical isolates from The Cleveland Clinic Foundation (Cleveland, Ohio), St. Francis Hospital (Wichita, Kans.), St. Vincent Hospital and Medical Center (Portland, Oreg.), and Northwestern Memorial Hospital (Chicago, Ill.) were collected and then retested for their susceptibility to the new ,-lactams singly and in combination with amikacin. Synergy analysis was determined by the checkerboard broth dilution technique, confirmed by a limited number of bactericidal concentration isobolograms and kill curves. Some additional organisms were tested, including several with resistance to one or more of the five broad-spectrum drugs to detect their possible conversion from resistantto-susceptible MIC results by the addition of another antimicrobial agent.MATERALS AND METHODS Antibiotics. The broad-spectrum drugs utilized in all phases of this study were supplied by the following manufacturers: amikacin, Bristol Laboratories, Syracuse, N.Y.; cefoperazone, Pfizer Inc., New York, N.Y.; cefotaxime, Hoechst-Roussel Pharmaceuticals Inc., Somerville, N.J.; ceftazidime, Glaxo Inc., Research Triangle Park, N.C.; moxalactam, Eli Lilly & Co., ...