Antimicrobial susceptibility of Neisseria gonorrhoeae in Cuba (1995-1999): implications for treatment of gonorrhea

BACKGROUND: Antibiotic-resistant strains of Neisseria gonorrhoeae, especially those resistant to penicillin and tetracycline, have spread with remarkable rapidity in many Caribbean countries. GOAL: The goal of the study was to survey the antibiotic susceptibilities of N gonorrhoeae strains isolated from 1995 to 1999 in Cuba and to discuss the impact of antimicrobial resistance on the management of gonorrhea in the country. STUDY DESIGN: Susceptibility of the strains to penicillin, tetracycline, cefuroxime, ceftriaxone, ciprofloxacin, spectinomycin, and azithromycin were determined by an agar dilution method. RESULTS: Penicillin and tetracycline resistance was noted in 60.8% and 54.2%, respectively, of the N gonorrhoeae strains tested. A total of 63.35 (76/120) of the N gonorrhoeae strains exhibited plasmid-mediated resistance to penicillin, tetracycline, or both. Strains with chromosomally mediated resistance to these antibiotics accounted for 10% (12/120) of the strains. The strains were susceptible to ceftriaxone, cefuroxime, spectinomycin, and ciprofloxacin. One strain's ciprofloxacin MIC was 0.125 mircog/ml. Of the 52 strains tested, 23.1% displayed intermediate resistance to azithromycin. CONCLUSIONS: N gonorrhoeae strains exhibited a high frequency of resistance and multiresistance to penicillin and tetracycline. Therefore, these antibiotics should no longer be used to treat gonococcal infections in Cuba and should be substituted with effective drugs such as third-generation cephalosporins, spectinomycin, and fluoroquinolones. The detection of intermediate resistance to azithromycin and ciprofloxacin underlines the importance of periodic surveillance for susceptibility of N gonorrhoeae strains to antimicrobials agents used as primary therapy for gonorrhea.     

Antimicrobial sensitivity of Neisseria gonorrhoeae. Comparison of penicillinase producing and non-penicillinase producing strains.

The sensitivity of 42 strains of penicillinase producing Neisseria gonorrhoeae (PPNG) and 46 strains of non-PPNG was tested against benzyl penicillin, spectinomycin, erythromycin, cefuroxime, ceftriaxone, tetracycline, sulphamethoxazole, and trimethoprim. The minimum inhibitory concentrations (MICs) of all antimicrobials, except trimethoprim and ceftriaxone, differed significantly for PPNG and non-PPNG strains. Ceftriaxone was the most active compound tested, the MIC for all strains being less than or equal to 0.015 mg/1. PPNG were less sensitive than non-PPNG strains to spectinomycin. It remains to be seen whether the increase in prevalence of PPNG strains is followed by a gradual increase in low level resistance to spectinomycin as well as the occasional finding of high level resistance to this antibiotic.     

Incidence of penicillinase producing Neisseria gonorrhoeae (PPNG) strains and susceptibility of gonococcal isolates to antibiotics in Benin City, Nigeria.

Of 53 strains of Neisseria gonorrhoeae isolated in Benin City, Nigeria, in February 1983 to October 1984, 46 (87%) produced penicillinase. The minimum inhibitory concentrations (MICs) of penicillin G and ampicillin for these isolates were between 1 mg/l and and 50 mg/l. About 48% (22/46) of the penicillinase producing strains were also resistant to streptomycin, cotrimoxazole, and ampicillin and cloxacillin. All 53 isolates were sensitive to tetracycline, erythromycin, amoxycillin and clavulanic acid, nalidixic acid, spectinomycin, and the penicillinase stable cephalosporins. The high incidence of resistance may have been the result of indiscriminate and unsupervised use of antibiotics before patients presented for proper treatment in clinics and hospitals.     

Antimicrobial susceptibility of Neisseria gonorrhoeae isolated in Durban, South Africa.

One hundred and forty clinical isolates of Neisseria gonorrhoeae were screened for production of penicillinase by the intralactam strip method and chromogenic cephalosporin test. Minimum inhibitory concentrations (MICs) of penicillin, ampicillin, tetracycline, cefoxitin, cefuroxime, cefotaxime, sulphamethoxazole-trimethoprim (ratio 19/1), and spectinomycin, were measured for 100 strains by the agar dilution method. Seven (5%) of the 140 isolates were identified as penicillinase producing N gonorrhoeae (PPNG). The MICs of penicillin for the seven PPNG strains ranged from 0 X 25 mg/1 to 2 mg/1. Of the 93 non-PPNG strains, 80 (86%) were fully susceptible to penicillin with MICs ranging from 0 X 0037 mg/1 to 0 X 06 mg/1 and 13 (14%) were of intermediate penicillin resistance with MICs greater than or equal to 0 X 125 mg/1. Of the 100 isolates tested, 86% were fully susceptible to tetracycline with MICs of less than 1 mg/1. No spectinomycin resistant strains were encountered in this study. All gonococcal strains were susceptible to the cephalosporins tested as well as to sulphamethoxazole-trimethoprim.     

Antimicrobial susceptibility of Neisseria gonorrhoeae isolated in Durban, South Africa

One hundred and forty clinical isolates of Neisseria gonorrhoeae were screened for production of penicillinase by the intralactam strip method and chromogenic cephalosporin test. Minimum inhibitory concentrations (MICs) of penicillin, ampicillin, tetracycline, cefoxitin, cefuroxime, cefotaxime, sulphamethoxazole-trimethoprim (ratio 19/1), and spectinomycin, were measured for 100 strains by the agar dilution method. Seven (5%) of the 140 isolates were identified as penicillinase producing N gonorrhoeae (PPNG). The MICs of penicillin for the seven PPNG strains ranged from 0 X 25 mg/1 to 2 mg/1. Of the 93 non-PPNG strains, 80 (86%) were fully susceptible to penicillin with MICs ranging from 0 X 0037 mg/1 to 0 X 06 mg/1 and 13 (14%) were of intermediate penicillin resistance with MICs greater than or equal to 0 X 125 mg/1. Of the 100 isolates tested, 86% were fully susceptible to tetracycline with MICs of less than 1 mg/1. No spectinomycin resistant strains were encountered in this study. All gonococcal strains were susceptible to the cephalosporins tested as well as to sulphamethoxazole-trimethoprim.     

Antimicrobial susceptibility of Neisseria gonorrhoeae isolates from a military population in San Diego

Neisseria gonorrhoeae isolates were studied to determine their patterns of antimicrobial susceptibility and possible chemotherapeutic implications. Of 370 consecutive isolates, 32 (8.7%) were penicillinase-producing N. gonorrhoeae (PPNG). The remaining 338 were subjected to disk-diffusion tests, and those apparently resistant to penicillin, tetracycline, or spectinomycin were tested by an agar-dilution method. The dilution test showed that 5.4% (20/370) were penicillin-resistant, non-PPNG strains, of which 100%, 90%, and 45% were also resistant to tetracycline, cefoxitin, and erythromycin, respectively. No resistance to spectinomycin or ceftriaxone was demonstrated, although there was an association between minimum inhibitor concentrations (MICs) of penicillin of greater than or equal to 1.0 microgram/ml and increased MICs of ceftriaxone. The overall incidence of penicillin resistant isolates, including PPNG, was 14.1% (52/370). Of the 20 penicillin-resistant, non-PPNG strains, all were also resistant to tetracycline, and another 21 exhibited tetracycline resistance but were sensitive to penicillin. The in-vitro data suggested that: (1) neither penicillin, tetracycline, nor cefoxitin were acceptable drugs for routine treatment of gonorrhea in our population during the study period; (2) spectinomycin and ceftriaxone continue to demonstrate adequate in-vitro activity against N. gonorrhoeae despite increasing in-vitro resistance to penicillin; and (3) non-plasmid-mediated resistance to penicillin may predict future resistance to ceftriaxone.     

Antimicrobial susceptibility of Neisseria gonorrhoeae in Harare, Zimbabwe. Relationship to serogroup

The authors investigated one hundred fifty-four isolates of Neisseria gonorrhoeae obtained from men, women, and infants in Harare, Zimbabwe, for in vitro susceptibility to various antibiotics and for reactivity with serogrouping antisera. The authors found sixty-four (42%) isolates to be WI serogroup and 90 (58%) to be WII/III. One hundred three isolates were penicillinase-producing N. gonorrhoeae (PPNG); although all of these showed resistance to penicillin, 14 isolates had an MIC to penicillin of less than 10 mg/L. All of these 14 isolates were WI serogroup. Twenty-seven of the 51 non-PPNG showed in vitro resistance to penicillin (MIC greater than 1.25 mg/L). All but one of these chromosomally resistant isolates were WII/III serogroup. With cefuroxime, tetracycline, and erythromycin, 10-15% of isolates had MICs greater than accepted breakpoints. Most isolates were susceptible to thiamphenicol, and all were susceptible to ciprofloxacin, kanamycin, and spectinomycin. The authors noted that WI isolates, whether PPNG or not, were consistently more susceptible to antibiotics than WII/III isolates. Only with kanamycin and spectinomycin were the MICs of the two serogroups similar.     

Patterns of antibiotic susceptibility of gonococci isolated in Hong Kong, 1987-1990.

Among the 14,528 strains of Neisseria gonorrhoeae isolated from the Government Social Hygiene Sexually Transmitted Disease (STD) Clinics in Hong Kong between 1987 and 1990, there has been a trend toward a decrease in the percentage of penicillin resistant strains in both penicillinase-producing and nonpenicillinase producing N. gonorrhoeae (PPNG and non-PPNG) and an increase in moderate resistant strains, whereas the proportion of sensitive strains has remained stable, except for a small increase in 1990. Presently, PPNG still accounts for 31% of all isolates. In early 1991, 100 consecutive isolates were tested for minimum inhibitory concentrations (MIC) against 6 commonly used antibiotics. Although ofloxacin has been used as the first-line treatment for gonorrhea for the last 5 years, there is still no sign of in vitro resistance. Two isolates with high-level tetracycline resistance (MIC greater than 16 mg/l) were detected that have not been seen before. Sensitivity to spectinomycin, cefuroxime, and ceftriaxone has also been maintained, and these drugs can probably be recommended as alternative treatments in noncompliant cases. Analysis of location of contact shows an increasing proportion of cases of gonorrhea from overseas, particularly from parts of China. Comparison with the limited information published in the region shows that the population sampled can be very heterogeneous. With the continued flux of international travel, one should be extremely careful when trying to get an accurate assessment of epidemiologic data.     

Single-dose minocycline in the treatment of gonococcal urethritis. Clinical efficacy in relation to bacterial resistance and its effects on associated Chlamydia trachomatis infections.

Seventy-two men with gonococcal urethritis were given a single 300-mg dose of minocycline. The failure rate was 13% and the trial was terminated at an early stage. Failure was correlated with increased resistance of Neisseria gonorrhoeae to minocycline. The activity of penicillin, spectinomycin, erythromycin, tetracycline, sulphamethoxazole, cefuroxime, cefotaxime, rosamicin, thiamphenicol, and piperacillin against N. gonorrhoeae were examined in vitro. With the exception of spectinomycin, parallel patterns of resistance to the other antibiotics and minocycline were found. Resistance to spectinomycin was not found, confirming the usefulness of this antibiotic in the treatment of gonorrhoea. The incidence of PGU was significantly lower after a single dose of minocycline than in previous studies.     

Single-dose minocycline in the treatment of gonococcal urethritis. Clinical efficacy in relation to bacterial resistance and its effects on associated Chlamydia trachomatis infections.

Seventy-two men with gonococcal urethritis were given a single 300-mg dose of minocycline. The failure rate was 13% and the trial was terminated at an early stage. Failure was correlated with increased resistance of Neisseria gonorrhoeae to minocycline. The activity of penicillin, spectinomycin, erythromycin, tetracycline, sulphamethoxazole, cefuroxime, cefotaxime, rosamicin, thiamphenicol, and piperacillin against N. gonorrhoeae were examined in vitro. With the exception of spectinomycin, parallel patterns of resistance to the other antibiotics and minocycline were found. Resistance to spectinomycin was not found, confirming the usefulness of this antibiotic in the treatment of gonorrhoea. The incidence of PGU was significantly lower after a single dose of minocycline than in previous studies.     

Susceptibility of penicillinase-producing and non-penicillinase-producing strains of Neisseria gonorrhoeae isolated in Durban, South Africa, to 15 beta-lactam antibiotics

Using two different inoculum sizes (10(4) and 10(7) organisms), we tested 35 penicillinase-producing (PPNG) and 72 non-PPNG strains of Neisseria gonorrhoeae falling into three categories (penicillin-sensitive, intermediately resistant, and resistant) by the agar-dilution method against 15 beta-lactam antibiotics. With the exception of penicillin, ampicillin, amoxicillin, and cephradine, the isolates were uniformly sensitive to all the other antibiotics tested (including spectinomycin, tetracycline, rosoxacin, sulfamethoxazole-trimethoprim [19:1 ratio], and kanamycin). Ceftriaxone and cefotaxime were the two most active compounds tested; all strains were inhibited at concentrations of 0.007 and 0.015 microgram/ml, respectively. Isolates with intrinsic resistance to penicillin were less susceptible to cefoxitin and cefuroxime than were PPNG strains. The effect of inoculum size varied for the different antibiotics; penicillin and cefaclor showed this effect only with PPNG strains, whereas for ampicillin and amoxicillin it was also seen with non-PPNG strains. Cephamandole showed this effect with both penicillin-sensitive and PPNG strains. In view of the increasing resistance to penicillin, we would recommend that alternative drugs be used as first line therapy for gonorrhea in South Africa.     

Chromosomal resistance to antibiotics in gonococci from Bahrain

Ninety-one isolates of non-penicillinase-producing Neisseria gonorrhoeae from patients in Bahrain were tested for serotype, auxotype, and antibiotic susceptibility. Ten serovars and three auxotypes were found. Of the 91 isolates, 49 (54%) were serovar IB-5/7, 59 (65%) had a penicillin MIC greater than or equal to 1 mg/l, 39 (45%) had a cefuroxime MIC greater than or equal to 0.5 mg/l, and 63 (69%) had a tetracycline MIC of greater than or equal to 4 mg/l. No spectinomycin or high-level tetracycline resistance was seen. Seventy of the 91 isolates were tested against ciprofloxacin and ceftriaxone, and 40 (57%) and 26 (37%) had MICs greater than or equal to 0.03 mg/l, respectively. DNA from two penicillin-resistant isolates was capable of transforming recipient strain FA19 to donor level of penicillin and cephalosporin resistance in four steps. The first three steps were indicative of the acquisition of known resistance mutations. The existence of the fourth level transformants, with the ability of donor DNA to transform strain FA140 to higher levels of resistance, suggest the presence of another resistance mutation.     

Penicillinase-producing Neisseria gonorrhoeae isolates from different localities in south east Asia. Susceptibility to 15 antibiotics.

Sixty four penicillinase-producing Neisseria gonorrhoeae (PPNG) and 24 non-penicillinase-producing (non-PPNG) strains isolated from six different south east Asian localities were tested by the agar dilution method against 15 antibiotics. All isolates were susceptible to spectinomycin and sulphamethoxazole-trimethoprim (19:1 ratio). A large proportion of both PPNG and non-PPNG strains showed, however, a decreased susceptibility to tetracycline, kanamycin, and erythromycin: 49% with minimum inhibitory concentrations (MICs) of tetracycline greater than or equal to 2 micrograms/ml, 34% with MICs of kanamycin greater than or equal to 32 micrograms/ml, and 80% with MICs of erythromycin greater than or equal to 2 micrograms/ml. These MIC cut-off values were chosen since they are close to the highest concentrations of these antibiotics attainable in serum after drug administration. Resistance to these antibiotics was not related to penicillinase production and does not appear to be confined to gonococci isolated from one particular locality. Strains showing resistance concurrently to two or three of these drugs were often isolated from different south east Asian countries. All eight cephalosporins tested were effective against both PPNG and non-PPNG strains. On a weight to weight basis the new cephalosporins--namely, moxalactam, cefoperazone, cefotaxime, and ceftriaxone--were the most effective. In contrast to those of cefoxitin, cefuroxime, moxalactam, and cefoperazone the MICs of cefamandole, cefotaxime, and ceftriaxone were significantly affected when the inoculum size was increased from 10(3) to 10(6) colony forming units (cfu).     

Penicillinase-producing Neisseria gonorrhoeae isolates from different localities in south east Asia. Susceptibility to 15 antibiotics

Sixty four penicillinase-producing Neisseria gonorrhoeae (PPNG) and 24 non-penicillinase-producing (non-PPNG) strains isolated from six different south east Asian localities were tested by the agar dilution method against 15 antibiotics. All isolates were susceptible to spectinomycin and sulphamethoxazole-trimethoprim (19:1 ratio). A large proportion of both PPNG and non-PPNG strains showed, however, a decreased susceptibility to tetracycline, kanamycin, and erythromycin: 49% with minimum inhibitory concentrations (MICs) of tetracycline greater than or equal to 2 micrograms/ml, 34% with MICs of kanamycin greater than or equal to 32 micrograms/ml, and 80% with MICs of erythromycin greater than or equal to 2 micrograms/ml. These MIC cut-off values were chosen since they are close to the highest concentrations of these antibiotics attainable in serum after drug administration. Resistance to these antibiotics was not related to penicillinase production and does not appear to be confined to gonococci isolated from one particular locality. Strains showing resistance concurrently to two or three of these drugs were often isolated from different south east Asian countries. All eight cephalosporins tested were effective against both PPNG and non-PPNG strains. On a weight to weight basis the new cephalosporins--namely, moxalactam, cefoperazone, cefotaxime, and ceftriaxone--were the most effective. In contrast to those of cefoxitin, cefuroxime, moxalactam, and cefoperazone the MICs of cefamandole, cefotaxime, and ceftriaxone were significantly affected when the inoculum size was increased from 10(3) to 10(6) colony forming units (cfu).     

Treatment of gonorrhoea and susceptibility to antimicrobials of PPNG and non-PPNG strains in Jamaica.

Of 1400 patients in Jamaica screened for uncomplicated gonorrhoea, 54% (753 patients) were culture positive. Of the 459 patients who complied with the terms of the study, 97% (211/218) of those treated with aqueous procaine penicillin G were cured compared with 94% (227/241) of those treated with ampicillin. Penicillinase producing Neisseria gonorrhoeae (PPNG) strains were identified for the first time during the study, and 10 patients infected with PPNG strains (two treated with penicillin, eight with ampicillin) contributed to the 21 treatment failures. The in vitro susceptibility of eight antimicrobial agents for 629 non-PPNG and 20 PPNG strains was estimated. Of the non-PPNG isolates, 8% had an MIC of 1 mg/l or more of penicillin, 11% were resistant to this concentration of ampicillin, 32% to tetracycline, and under 1% to the same concentration of cefuroxime and erythromycin. Fewer than 2% of the isolates were resistant to 2 mg/l or more thiamphenicol, and all isolates were susceptible to spectinomycin and trimethoprimsulphamethoxazole (at a ratio of 1:19). Significantly more strains from the 21 treatment failures were resistant to penicillin (52%) or ampicillin (62%) compared with 7% strains resistant to penicillin and 4% to ampicillin from the successfully treated group.     

Antimicrobial susceptibility of Neisseria gonorrhoeae in Zaire: high level plasmid-mediated tetracycline resistance in central Africa.

OBJECTIVE--To determine the in vitro antimicrobial susceptibility of gonococcal strains isolated in 1988 among female prostitutes in Kinshasa, Zaire and to characterise strains with high level tetracycline resistance. METHODS--Minimal inhibitory concentrations of 8 antimicrobials were measured by agar dilution technique. Plasmid-profiles and serovars were determined. RESULTS--Two hundred and thirteen strains of Neisseria gonorrhoeae were tested of which 59% were beta-lactamase producers and an additional 21% showed intermediate or chromosomal resistance to penicillin (MIC = 0.5-8 mg/l). Eleven percent of the strains were resistant to the combination sulfamethoxazole-trimethoprim (MIC greater than 8 mg/l) and 57% of the isolates showed decreased susceptibility to thiamphenicol (MIC = 1-4 mg/l). All strains were sensitive to spectinomycin, norfloxacin and ceftriaxone and moderately sensitive to kanamycin. Chromosomal resistance to tetracycline was observed in 45% of strains (MIC = 2-8 mg/l). Ten percent were highly resistant to tetracycline (TRNG, MIC = 16-128 mg/l) and were shown to carry a plasmid borne Tet M determinant; such strains were not found in Kinshasa in 1985. TRNG belonged to 4 different serovars, which were also the dominant serovars in non-TRNG. CONCLUSION--These findings illustrate the high frequency of multiresistant gonococci in Zaire and suggest that high level tetracycline resistant strains of N. gonorrhoeae have become endemic in Central Africa.     

356株淋病奈瑟菌对抗菌药物敏感性的分析

目的　了解淋病奈瑟菌对青霉素、四环素、环丙沙星、头孢曲松、红霉素、卡那霉素、庆大霉素、壮观霉素、诺氟沙星、氧氟沙星和头孢噻肟的敏感性。方法　用纸片和琼脂稀释法测定药物敏感性 ,测定β 内酰胺酶。结果　 3 56株淋病奈瑟菌对头孢曲松、头孢噻肟和壮观霉素的耐药性分别增至 7.6% ,9.4%和 2 4.5% ,其余药物的耐药性均显著增加 ;检出 β 内酰胺酶阳性菌 81株。结论　河南地区淋病奈瑟菌对青霉素、四环素、红霉素、诺氟沙星、氧氟沙星的耐药性相当高 ,对头孢曲松、头孢噻肟和壮观霉素的耐药性有增加趋势 ,但此三种药仍可作为治疗淋病的一线药物     

Antimicrobial susceptibility, auxotype and plasmid content of Neisseria gonorrhoeae in northern Tanzania: emergence of high level plasmid mediated tetracycline resistance.

OBJECTIVE--To study the antimicrobial susceptibility, plasmid content, auxotype and serogroup of strains of Neisseria gonorrhoeae isolated from an urban population of STD clinic attenders in Northern Tanzania. METHODS--The minimum inhibitory concentrations of nine common antimicrobial agents were measured by the agar dilution method against 130 strains of Neisseria gonorrhoeae isolated in a free government STD clinic in Mwanza town. The auxotype, plasmid content and serogroup of these strains were also determined by conventional techniques. RESULTS--65 strains (50%) were penicillinase producers (PPNG), and 34 (26%) exhibited chromosomally mediated resistance to penicillin. Seven (5%) were sensitive to tetracycline; 78 (60%) showed intermediate levels of resistance, and 45 (35%) had high level plasmid mediated resistance (TRNG), all of which carried a 25.2 MDa plasmid. 79 strains (61%) showed decreased sensitivity to trimethoprim-sulphamethoxazole, and five (4%) were resistant to this agent. All isolates were fully sensitive to spectinomycin, azithromycin, cefotaxime, cefuroxime, norfloxacin and ciprofloxacin. One hundred and one strains (78%) were of type W11/111, 22 type W1, and seven cross reacting strains. The W1 strains were significantly more likely to be carrying plasmid mediated resistance to both penicillin and tetracycline. Six different auxotypes were present, the major type requiring proline. Plasmid profiles showed the presence of both the 3.2 MDa and the 4.4 MDa beta-lactamase encoding plasmids. CONCLUSION--a high proportion of gonococcal isolates remain resistant to penicillin in this region, and most isolates are now also resistant to tetracycline, with the emergence of plasmic mediated tetracycline resistance. Trimethoprim-sulphonamide sensitivity is also decreasing. The population of strains is heterogeneous, and both African and Asian beta-lactamase encoding plasmids are present.     

解脲支原体对12种药物体外敏感性研究

为了解解脲支原体的药物敏感情况,用液体稀释法对５０株ＵＵ进行了罗红霉素等１２种药物的体外敏感性测定。结果表明,大环内脂类药物,尤其是罗红霉素对ＵＵ的体外抑制作用最强,ＭＩＣ９０为２ｍｇ／Ｌ;     

Activity in vitro of ten antimicrobial agents against Neisseria gonorrhoeae. A study of the correlation between the sensitivities.

105 Belgian strains of Neisseria gonorrhoeae were tested for their sensitivity to penicillin, ampicillin, rifampicin, erythromycin, tetracycline, streptomycin, spectinomycin, sulphamethoxazole, trimethroprim, and a combination of sulphamethoxazole and trimethroprim in a 5:1 ratio. Distribution and median values of minimum inhibitory concentrations (MICs) are given and discussed. 42 per cent. of strains were relatively resistant to penicillin (MIC greater than or equal to 0-04 mug/ml.), but only 2 per cent. showed high-level resistance (MIC greater than or equal to 0-38 mug/ml.), which is comparable with the prevalence of decreased sensitivity found in other European countries. A significant positive correlation (P less than or equal to 0-01, rank correlation coefficient) is found between the sensitivities to penicillin, ampicillin, erythromycin, tetracycline, and streptomycin, except for the ampicillin-erythromycin and ampicillin-tetracycline pairs. Rifampicin is correlated with tetracycline. No correlation is found between the sensitivities to spectinomycin and any of the other drugs. The combination of sulphamethoxazole and trimethoprim in a 5:1 ratio also shows a significant positive correlation with penicillin and ampicillin and with sulphamethoxazole and trimethoprim separately.