Susceptibility of Neisseria gonorrhoeae to cefpodoxime: determination of MICs and disk diffusion zone diameters

Abstract

We studied the susceptibilities of 77 strains of Neisseria gonorrhoeae to four antibiotics: cefpodoxime, ceftriaxone, penicillin, and tetracycline. All strains were susceptible to ceftriaxone. Cefpodoxime MICs (range, 0.001 to 0.125 ,ug/ml) were parallel to and approximately four times those of ceftriaxone, and all strains will probably be considered susceptible to cefpodoxime. Disk diffusion zone diameters for cefpodoxime ranged from 35 to 57 mm. Of the strains, 32% were penicillin resistant and 51% were tetracycline resistant (MIC,.2 ,ug/ml). Susceptibility measurements were consistent for disk diffusion zone diameter and MIC, with an overall agreement of 215 of 225 (96%) for ceftriaxone, penicillin, and tetracycline combined. On the basis of these in vitro data, cefpodoxime should be evaluated in the treatment of gonorrhea.There are two major limitations in the current management of patients with gonorrhea. The first limitation is the shortage of effective antimicrobial agents which can be given in a single oral dose. Oral medications can improve acceptance of treatment, and single-dose therapy makes it unnecessary to rely on patient compliance to complete therapy at home. Quinolones (3) and cephalosporins (1) have both been useful in the oral treatment of gonorrhea. Tetracyclines (10) and penicillin (5), however, are no longer reliable therapeutic agents because of the emergence and dissemination of resistant strains of Neisseria gonorrhoeae.The second limitation is the exceptional difficulty in testing for antibiotic resistance in N. gonorrhoeae. Few clinical laboratories currently do more than test for P-lactamase production (7). The fastidious growth requirements of N. gonorrhoeae have precluded the use of the usual broth microdilution and disk diffusion technologies for routine susceptibility testing. Reference laboratories provide information about resistance patterns in different geographical regions, but this may be of limited value in treatment decisions made at the time of diagnosis.We studied the susceptibility of N. gonorrhoeae to cefpodoxime, a new oral cephalosporin. This agent is administered as cefpodoxime proxetil, an ester prodrug, which is metabolized to active drug (cefpodoxime) by intestinal esterases (13). Cefpodoxime is resistant to many bacterial P-lactamases and has an antimicrobial spectrum similar to that of cefixime but with greater activity for gram-positive organisms (9). In one in vitro study, cefpodoxime had activity superior to that of cefuroxime and comparable with that of ceftriaxone for N. gonorrhoeae (12). Cefpodoxime is well absorbed and well tolerated and has a plasma half-life of 2.7 h (2); after a single oral dose of 200 mg, levels in plasma exceed 1 ,ug/ml for more than 5 h.We compared susceptibility results for cefpodoxime, ceftriaxone, penicillin, and tetracycline. Ceftriaxone is currently the preferred therapy for the treatment of gonorrhea in the United States (4). A dose of 250 mg given intramuscularly is essentially 100% curative for gonorrhea infection of the a...

Worldwide Susceptibility Rates of Neisseria gonorrhoeae Isolates to Cefixime and Cefpodoxime: A Systematic Review and Meta-Analysis

“…Among the 25 included studies, only four [27] , [28] , [29] , [30] reported all seven of the categories in our data matrix, seven [31] , [32] , [33] , [34] , [35] , [36] , [37] reported data on six of these categories, ten [38] , [39] , [40] , [41] , [42] , [43] , [44] , [45] , [46] , [47] provided information on five of these categories, and four [48] , [49] , [50] , [51] reported data of only four of these categories ( Table 2 ). The quality of an included study was negatively scored in particular when it failed to describe the study population or NG isolate identification method.…”

“…No significant publication bias was found (the Begg rank correlation test, P = 0.197). The susceptibility rate of NG isolates to cefpodoxime was lower than that to cefixime (92.8% vs. 99.8%, χ 2 = 951.809, P<0.001); the former ranged from 89.9% (95% CI: 84.5%–93.5%) to 100% (95% CI: 95.6%–100%) over the five included studies concerning cefpodoxime susceptibility ( Figure 3 ) [27] , [30] , [47] , [50] , [51] . Four reported cefpodoxime susceptibility rates of 100%, and one documented a rate of 89.9%.…”

Antimicrobial susceptibility testing of Neisseria gonorrhoeae and implications for epidemiology and therapy.

“…Several strains had cefmetazole MICs of .4 ,ug/ml, suggesting that they might not be eradicated with single-dose cefmetazole. To a lesser extent, this has been shown with other cephalosporins such as cefuroxime (75), cefpodoxime (35,93), cefoxitin (75) and even ceftriaxone (50, 102). The very widespread use of cephalosporins could conceivably accelerate the process of selecting less and less 1-lactamsusceptible strains in the way that CMRNG increased slowly in incidence over the decades during which penicillin was the drug of choice for gonorrhea.…”