Journal of Antimicrobial Chemotherapy (1978) 4 (Suppl. B), 61-64

The susceptibility of Neisseria gonorrhoeae to cefoxitin sodium

L Phillips

Minimum inhibitory concentrations (MICs) of cefoxitin sodium and benzylpenicillin for 48 gonococci were compared. Although benzylpenicillin was much more active on sensitive strains, the two agents similarly inhibited less-sensitive strains at a concentration of about 1 mg/1. Cefoxitin activity was not affected by the production of j3-lactamase by 5 /J-lactamase-producing gonococci isolated in the U.K. and the U.S.A., but cephaloridine, cephalothin, cephalexin, cephradine, cefamandole, cefazolin, and cefuroxime were all less active against large than against small inocula. Despite this, cefuroxime was, weight for weight, more active than cefoxitin on large inocula. Introduction

A considerable amount of previous work has shown that cephalosporins resemble penicillins in their activity on gonococci. Minimum inhibitory concentrations (MICs) usually cover a range and there is a good correlation between MICs of different agents (Phillips, King, Warren, Watts & Stoate, 1976). This paper presents information on the in vitro activity of cefoxitin sodium on gonococci, in comparison with that of penicillin, and also on the activity of cefoxitin against /Mactamase-producing gonococci, in comparison with a number of cephalosporins. Materials and methods

The gonococci were mostly isolated from patients attending the Venereal Diseases Department of St. Thomas' Hospital. They included the only ^3-lactamase-producing strain (STH) that we have isolated (Phillips, 1976). They also included other /J-lactamaseproducing strains isolated in London (VDRL), Liverpool (Liv) and in the U.S.A. (USA 1 and 2, 76-061782 and 76-073389, respectively). Table I. Activity of benzylpenicillin and cefoxitin on 48 gonococci. Percentage of isolates

Benzylpenicillin Cefoxitin

0-007

0 •015

0-03

10

56

15

O3O5-7453/78/O7O1-BO61 Wl.00/0

MIC (mg/1) 0-06 012 2

8 15

0-25

0-5

10

2 73

6 6

6

61 © (1978) The Biritish Society for Antimicrobial Chemotherapy

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Department of Microbiology, St Thomas' Hospital Medical School, London, England

STH VDRL

Liv

t The 4 figures under each head represent MICs for inocula of loa, 10S, 10' and lo6 c.f.u.

See text for explanation of codes.

cephaloridine cephalothin cephalexin cephradine cefazolin cefamandole cefuroxime cefoxitin

Antibiotic

MICs for increasing inocula of isolates* of 8-lactarnase-producinggonococci : USA 1

Table 11. Activity of 7 cephalosporins and cefoxitin on 5 /I-lactarnase-producing gonococci

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USA 2

Susceptibility of Nehseria gonorrhoeae

63

Sensitivity tests were performed on Oxoid diagnostic sensitivity test agar (DST Oxoid CM261) containing 6% saponin-lysed horse blood and suitable concentrations of antibiotic. The inoculum consisted of approximately 10* colony forming units (c.f.u.) from a suspension of organisms in lysed-blood broth, delivered by a multiple inoculator (Phillips et al, 1976). Sensitivities of the whole collection of gonococci were determined for benzylpenicillin and cefoxitin. The activity of cephaloridine, cephalexin, cephalothin. cephradine, cefamandole, cefazolin, cefuroxime, and cefoxitin was examined against different inocula of /Mactamase-producing gonococci.

The MICs of penicillin and cefoxitin for 48 isolutes of gonococci are shown in Table I. Penicillin MICs showed the expected range from 0015 to 1 mg/1, with a bimodal distribution. MICs of cefoxitin ranged from 0-12 to 1 mg/1 and were not bimodally distributed. There were no /9-lactamase producers in this series. When MICs of benzylpenicillin and cefoxitin were compared by the method of leastsquare analysis, they were seen to correlate well (regression coefficient: 0-89). It was also clear that penicillin-sensitive organisms were, weight-for-weight, considerably less sensitive to cefoxitin, but relatively penicillin-resistant organisms (MIC: 0-5 to 1 mg/1) were not much less- susceptible to cefoxitin than were penicillin-sensitive organisms. At a theoretical penicillin MIC of about 1 mg/1, the cefoxitin MIC was also approximately 1 mg/1. The activity of all the cephalosporins and cefoxitin against /J-lactamase-producing gonococci is shown in Table II. All the strains behaved similarly for each antibiotic. There was often an inoculum effect, most striking for cephaloridine (4- to more than 16fold over the 1000-fold range on inocula tested) and cefamandole (8- to 64-fold), and somewhat less for the other cephalosporins (1- to 8-fold). Cefoxitin alone showed no inoculum effect. In some compensation, cefuroxime was so active that even with large inocula, MICs never exceeded 012 mg/1 for any isolate. Discussion On the basis of these results, cefoxitin shows considerable promise as an anti-gonococcal antibiotic. Although, with MICs around 01 mg/1, it is, like cephradine and cephalexin, one of the less-active /J-lactam antibiotics against penicillin-sensitive organisms, it is only about 10 times less active, with MICs of around 1 mg/1 against relatively penicillinresistant organisms. In this respect, cefoxitin differs from most cephalosporins, which are about 100 times less active than benzylpenicillin on sensitive and relatively resistant organisms. The striking exception to this is cefuroxime, which is uniquely more active weight-for-weight than benzylpenicillin on relatively penicillin-resistant strains. These results are in keeping with those of Finland, Garner, Wilcox & Sabath (1976). Cefoxitin retains many of its advantages against j9-lactamase-producing gonococci. With small inocula, only cefamandole and cefuroxime are more active. This is in keeping with the results of Blog et al. (1977). However, all the cephalosporins showed a more-orless striking inoculum effect with a 1000-fold change in inoculum. Cefoxitin showed none. Despite this, cefuroxime remained more active weight-for-weight even against high inocula, because of its very high activity.

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Results

64

I. Phillips

On the basis of these results, cefoxitin has a place in the treatment of gonorrhoea caused both by /J-lactamase-producing and by non-/Mactamase producing gonococci, subject to confirmation by clinical trial. Acknowledgements I thank Dr K. Shannon for his contributions to this study and Dr A. E. Wilkinson, Dr A. Percival and Dr C. Thornsberry for the gift of ^-lactamase-producing gonococci.

Blog, F. B., Chang, A., De Koning, G. A. J., Oranje, A. P., Stolz, E., Bosscher-Koetsier, G., De Jonge-Suy, M. P. E., Michel, M. F., O'Neil, E., De Weerdt-Van Ameyden, S. & Gaastra, L. Penicillinase-producing strains of Neisseria gonorrhoeae isolated in Rotterdam. British Journal of Venereal Diseases 53: 98-100 (1977). Finland, M., Garner, C , Wilcox, C. & Sabath, L. D. Susceptibility of Neisseria gonorrhoeae to 66 antibacterial agents in vitro. Journal of the American Venereal Disease Association 2: 33-40 (1976). Phillips, I. j3-lactamase-producing penicillin-resistant gonococcus. Lancet ii: 656-7 (1976). Phillips, I., King, A., Warren, C , Watts, B. & Stoate, M. W. The activity of penicillin and eight cephalosporins on Neisseria gonorrhoeae. Journal of Antimicrobial Chemotherapy 2: 31-9 (1976).

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References

The susceptibility of Neisseria gonorrhoeae to cefoxitin sodium.

Journal of Antimicrobial Chemotherapy (1978) 4 (Suppl. B), 61-64 The susceptibility of Neisseria gonorrhoeae to cefoxitin sodium L Phillips Minimum...
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