A randomized trial of ciprofloxacin versus cefixime for treatment of gonorrhea after rapid emergence of gonococcal ciprofloxacin resistance in The Philippines.

From 1994 through 1996-1997, high-level ciprofloxacin resistance (minimum inhibitory concentration [MIC], > or = 4.0 microg/mL) increased from 9% to 49% of gonococcal isolates recovered from consecutive female sex workers in Cebu and Manila, The Philippines (P < .01). During 1996-1997, 105 female sex workers with gonorrhea were prospectively randomized to receive treatment with oral ciprofloxacin, 500 mg, or cefixime, 400 mg, and followed for test of cure. Neisseria gonorrhoeae was reisolated within 28 days after treatment from 1 (3.8%) of 26 women given cefixime versus 24 (32.3%) of 72 women given ciprofloxacin (P < .01). Treatment failure (reisolation of pretreatment auxotype/serovar) occurred in 14 (46.7%) of 30 women infected with strains with MICs of ciprofloxacin > or = 4.0 microg/mL versus 1 (3.6%) of 28 infected by strains with MICs < 4.0 microg/mL (P < .01). High-level, clinically significant gonococcal resistance to ciprofloxacin has rapidly emerged in The Philippines, and spread of fluoroquinolone resistance through commercial sex poses a threat to control of gonorrhea and prevention of human immunodeficiency virus infection and the acquired immunodeficiency syndrome.

Alterations within the quinolone resistance-determining regions of GyrA and ParC of Neisseria gonorrhoeae isolated in the Far East and the United States.

The genetic mutations within the quinolone resistance-determining regions (QRDRs) of gyrA and parC of 234 Neisseria gonorrhoeae strains isolated in the Far East and the United States, which exhibited either clinically significant ciprofloxacin resistance (CipR) or intermediate ciprofloxacin resistance (CipI) were characterized. A number of GyrA/ParC amino acid alteration patterns were identified, the most prevalent alteration pattern among CipR isolates being GyrA-91,95/ParC-Asp-86- > Asn (91,95/Asp-86- > Asn). Isolates containing 91,95/Asp-86- > Asn belonged to a number of A/S classes, penicillin/tetracycline resistance phenotypes, and plasmid profiles. These results strongly suggest that the continuing emergence of ciprofloxacin-resistant gonococci is not due to the spread of a single or a few strains but to numerous factors such as 'spread of existing strains, importation of new strains and, possibly, de novo development of ciprofloxacin resistance in previously susceptible strains.

Correlates of gonococcal infection and of antimicrobial-resistant Neisseria gonorrhoeae among female sex workers, Republic of the Philippines, 1996-1997.

From 1994 to 1997, the proportion of Neisseria gonorrhoeae highly resistant to ciprofloxacin (MIC >/=4 microg/mL) increased substantially among female sex workers (FSWs) in the Philippines. Among 1499 Filipina FSWs, we evaluated factors associated with gonococcal infection and with gonococcal antimicrobial resistance. By multivariate analysis, gonococcal infection was associated with sex with a new client, self-prescribed prophylactic antimicrobial use, work in a brothel, and inconsistent condom use and was negatively associated with registration status and vaginal hygiene practices. Factors associated with ciprofloxacin-resistant gonococci included: marital status, living alone, duration of sex work, and clinic site. Further, gonococci highly resistant to ciprofloxacin were isolated from 10 (11.5%) of 87 FSWs reporting self-prescribed antimicrobial use versus 44 (3.4%) of 1295 reporting no antimicrobial use (P<.001). Self-prescribed prophylactic antimicrobial use and inconsistent condom use could be important factors in the continued emergence of gonococcal antimicrobial resistance in the Philippines.

Syndromic approach to detection of gonococcal and chlamydial infections among female sex workers in two Philippine cities.

BACKGROUND: In many developing countries, STD control efforts often involve registration and periodic examinations of female sex workers (FSW). Non-availability of sensitive and specific diagnostic tests frequently constrain this approach. METHODS: A model for detection of Chlamydia trachomatis or Neisseria gonorrhoeae in FSW on the basis of risk assessment and examination was developed from data gathered in Manila and evaluated in a second city (Cebu) in the Republic of the Philippines. RESULTS: Gonococcal or chlamydial cervical infection was found in 23.3% of FSW in Manila and 37.0% in Cebu. Unregistered and younger FSW had greatest risk of chlamydial infection and/or gonorrhoea in both cities. In Manila, where gynaecologists performed the pelvic examinations, signs of cervical mucopus or cervical motion, uterine or cervical motion tenderness in women under < 25 years old or unregistered had positive predictive value (PPV) of 0.60 and sensitivity of 42.1% for cervical infection. In Cebu, where women were not examined by gynaecologists, the same model had high PPV, but a sensitivity of only 12.3%. CONCLUSIONS: Experience and training of clinicians undoubtedly can influence the yield of examination in syndromic management of cervical infection. Nevertheless, inexpensive and diagnostic tests are needed for detection of cervical infection in this population.

Molecular epidemiology, in 1994, of Neisseria gonorrhoeae in Manila and Cebu City, Republic of the Philippines.

BACKGROUND AND OBJECTIVES: Failure of gonococcal infections to respond to 500 mg of ciprofloxacin or 400 mg of ofloxacin has been reported from Australia, the United Kingdom, and the United States. Recently, high rates of decreased susceptibility to the fluoroquinolones have been detected in penicillinase-producing Neisseria gonorrhoeae in the Republic of the Philippines. GOALS: To assess the diversity of antimicrobial-resistant gonococcal strains isolated from female sex workers in Manila and Cebu City in the Republic of the Philippines in 1994. STUDY DESIGN: Isolates of N. gonorrhoeae isolated from 92 female sex workers in Manila (n = 28) and Cebu City (n = 64), respectively, were characterized by plasmid profile, auxotype/serovar class, and antimicrobial susceptibility profile. RESULTS: Plasmid-mediated resistance to penicillin or tetracycline was identified in 79.3% (73/92) of the isolates: penicillinase-producing N. gonorrhoeae (65/92; 70.7%), tetracycline-resistant N. gonorrhoeae (6/92; 6.5%), and penicillinase-producing/tetracycline-resistant N. gonorrhoeae (1/92; 1.1%). A beta-lactamase plasmid of 3.9 megadaltons was discovered. Of 54.3% (50/92) of strains resistant to nalidixic acid, 84% (42/50) of strains had minimum inhibitory concentrations of > or = 0.125 microgram/ml ciprofloxacin; penicillinase-producing N. gonorrhoeae (possessing the 3.05-, 3.2-, 3.9-, and 4.4-megadalton beta-lactamase plasmids, respectively) accounted for 68% (34/50) of these strains. CONCLUSIONS: In the Republic of the Philippines, gonococcal isolates resistant to penicillin or tetracycline accounted for 85.9% (79/92) of the isolates examined and included strains exhibiting resistance to fluoroquinolones. All gonococcal infections should be treated with antimicrobial therapies known to be active against all gonococcal strains to reduce the spread of strains exhibiting decreased susceptibilities to fluoroquinolones.

PIP: During July-October 1994 in the Philippines, Neisseria gonorrhoeae were isolated from 92 female sex workers in Manila and Cebu City. The purpose was to characterize the gonococcal strains by plasmid content, auxotype, serovar, and antimicrobial susceptibilities in order to examine the diversity of antimicrobial-resistant N gonorrhoeae strains in these sex workers. Penicillinase-producing N gonorrhoeae (PPNG) comprised 70.7% of the isolates. Strains with the 3.2-megadalton (Mda) beta-lactamase plasmid were more common in Cebu City than in Manila (57.8% vs. 28.6%; p = 0.02). They had significantly lower minimum inhibitory concentrations (MICs) to penicillin, tetracycline, ceftriaxone, ciprofloxacin, and erythromycin than did strains with 3.05-, 3.9-, or 4.4-Mda plasmid (p 0.01). One PPNG strain had a previously undescribed 3.9-Mda beta-lactamase plasmid. It also had a 24.5-Mda conjugative plasmid. Only 15.2% of all 92 isolates were susceptible to both penicillin and tetracycline. Tetracycline-resistant N gonorrhoeae (TRNG) comprised 6.5% of the isolates. 1.1% of isolates were resistant to both penicillin and tetracycline. 54.3% of all strains were resistant to nalidixic acid (fluoroquinolone), 84% of which had MICs of at least 0.125 mcg/ml ciprofloxacin. 68% of the nalidixic acid-resistant strains had 4.4 Mda beta-lactamase plasmids. 85.9% of all gonococcal isolates exhibited resistance to penicillin or tetracycline. They also included strains exhibiting resistance to fluoroquninolones. These findings reveal the need for periodic surveillance for resistance in N gonorrhoeae to the antimicrobial agents used for primary gonorrhea therapy in order to improve the treatments of choice.

Can the case-control method be used to assess the impact of water supply and sanitation on diarrhoea? A study in the Philippines.

PIP: This study had 2 objectives: 1) to determine whether a case-control approach is an effective measure for assessing the effect of improved sanitation on bacterial diarrhea, and 2) to assess the effects of environmental sanitation on diarrheal disease in Cebu. The study took place during the warm, rainy months (July-September) of 1985. The study population consisted of 281 children under 2 who were treated at 1 of 16 clinics for diarrhea due to Escherichia coli, salmonella, shigella, and Vibrio cholerae. The controls were 384 children under 2 who were brought to the clinics for respiratory ailments and did not have diarrhea. Environmental sanitation was classed as "good" if the bacterial count in the water supply was low (i.e., water was obtained from the municipal water supply or bore holes) and if excreta disposal was adequate (i.e., there were flush toilets, sealed latrines, or pit latrines). Water quantity was measured by the number of times the child was bathed. The effects of the exposure variables on the study children were determined by logistic regression analyses adjusted for confounding variables, which included sex, educational level of the household, breast feeding, attendance at well-baby clinics, number of children under 5 in the household, and frequency of bathing the child. The results of the study showed that improved sanitation reduced the episodes of bacterial diarrhea by 40%, and that case-control studies with sample sizes of about of about 500 cases and 500 controls are adequate to detect disease reductions of 33% or more.^ieng