Josephine M. Ehret

In vitro evaluations of condoms with and without nonoxynol 9 as physical and chemical barriers against chlamydia trachomatis, Herpes simplex virus type 2, and human immunodeficiency virus

Simulated in vitro intercourse conditions demonstrated that unlubricated latex condoms provide an effective physical barrier to high concentrations of Chlamydia trachomatis, herpes simplex virus type 2, and human immunodeficiency virus. However, since condoms can be damaged after manufacturing inspection and prior to use, latex condoms alone should not be perceived as absolute protection against STDs. Nonoxynol 9 used in conjunction with condoms provided additional, yet still not foolproof, protection against the three viruses.

Chlamydia trachomatis among Patients Infected with and Treated for Neisseria gonorrhoeae in Sexually Transmitted Disease Clinics in the United States

Context On the basis of studies of chlamydia and gonorrhea co-infection in the 1980s, guidelines recommend empirical treatment for chlamydia for patients receiving treatment for gonorrhea. The relevance of these recommendations to current practice is unknown. Contribution These 1995 data suggest that, in U.S. sexually transmitted disease clinics, the prevalence of Chlamydia trachomatis among patients infected with gonorrhea (20% in men, 42% in women) or treated for gonorrhea (19% in men, 35% in women) remains sufficiently high to warrant continued empirical therapy for chlamydia. Cautions These data are nearly a decade old. They may not apply in settings that are not sexually transmitted disease clinics. The Editors In the early 1980s, shortly after techniques for culturing Chlamydia trachomatis became available, program data and expert opinion suggested that C. trachomatis coexisted in up to 45% of patients infected with Neisseria gonorrhoeae (1). On the basis of these estimates, the U.S. Centers for Disease Control and Prevention (CDC) first suggested (1) and then formally recommended (2) that all patients treated for gonorrhea should also be treated for chlamydia. Presumptive chlamydia treatment in patients treated for gonorrhea (that is, co-treatment) has remained the standard of care, a recommendation recently renewed in the CDC Sexually Transmitted Diseases Treatment Guidelines, 2002 (3). Co-treatment was proposed as a strategy for chlamydia control at a time when chlamydia culture was performed only in research settings. Over the past two decades, diagnostic testing for C. trachomatis has dramatically improved (4). Nonetheless, many public clinics do not routinely test for C. trachomatis. Furthermore, even clinics that do test for chlamydia tend to use less sensitive, earlier-generation tests (enzyme immunoassay, DNA hybridization tests) (5) because the newer, more sensitive nucleic acid amplification tests (such as polymerase chain reaction [PCR]) are more expensive. To date, there are no accurate, rapid, point-of-care tests for chlamydia. Consequently, rapid testing (Gram stain, predominantly in men) is used for gonorrhea but not for chlamydia, and sensitive testing for gonorrhea remains more accessible in everyday practice than does chlamydia testing, particularly in public health settings where reimbursement for amplification tests is typically not available. The prevalence of sexually transmitted diseases (STDs) in the United States has changed notably since 1982, when co-treatment was introduced. Reported rates of gonorrhea in the United States have declined steadily from 418 per 100 000 persons in 1982 to 149 per 100 000 persons in 1995 to 129 per 100 000 persons in 2001 (6). National chlamydia trends have been difficult to determine because of increases in screening, test sensitivity, and case reporting. In regions where screening in women has been implemented for several years, rates of chlamydial infection seem to have decreased (6). If the prevalence of chlamydia among patients treated for gonorrhea has substantially decreased, co-treatment may no longer be indicated as a clinical or public health strategy. Despite the changes in testing technology and infection prevalences, few current data are available on the prevalence of chlamydia among patients treated for gonorrhea. However, over the past decade, estimates of chlamydial infection among persons infected with gonorrhea (that is, co-infection) have varied widely, ranging from 9% to 50% among men and 24% to 67% among women (7-21). Most of these studies, however, included small numbers of patients (7-12) or used less sensitive chlamydia tests (13-17). Furthermore, they addressed only the epidemiologic question of co-infection. Since treatment decisions must often be made before test results are available, the prevalence of chlamydia among patients treated for gonorrhea is more relevant than the prevalence among patients ultimately found to be infected with N. gonorrhoeae. Our analysis had two objectives. First, to investigate co-infection, we sought to determine the prevalence of chlamydia among patients at STD clinics who were infected with N. gonorrhoeae. Second, to assess the appropriateness of co-treatment, we sought to determine the prevalence of chlamydia among patients at STD clinics who were treated for gonorrhea, including those treated presumptively as sex partners of gonorrhea-infected persons. Methods Study Design We performed a cross-sectional analysis using baseline (enrollment) data collected from July 1993 through October 1995 for Project RESPECT, a randomized, controlled trial of counseling interventions (22). The trial was conducted among patients from public STD clinics in Baltimore, Maryland; Denver, Colorado; Long Beach, California; Newark, New Jersey; and San Francisco, California. All English-speaking patients at least 14 years of age who came to the clinics for an STD examination (evaluation of symptoms, screening or routine care, or contact with an infected partner) and who reported penilevaginal intercourse during the preceding 3 months were asked to participate. Participants found to be infected with HIV and men who identified themselves as homosexual or reported having a male sex partner during the preceding 12 months were excluded. All participants gave written, informed consent, and the institutional review boards at each site reviewed and approved the protocol. Overall, 43% of eligible patients agreed to participate in the 12-month intervention and follow-up. Study participants were routinely tested for gonorrhea, chlamydia, and several other STDs. Definitions For this analysis, we defined gonococcal infection as a positive culture for N. gonorrhoeae from a urethral or endocervical swab in men or women, respectively. We defined chlamydial infection as a positive PCR result from a urine specimen or endocervical swab in men or women, respectively. We included all participants with conclusive test results from both a gonorrhea culture and a chlamydia PCR. Nongonococcal urethritis was defined as the presence of at least 5 polymorphonuclear leukocytes per high-power field and absence of gram-negative intracellular diplococci on Gram stain. Mucopurulent cervicitis and pelvic inflammatory disease (PID) were defined according to the clinicians presumptive diagnosis at the initial visit. We considered patients to have been exposed to an STD if they had a referral card or reported that their partner was infected. We defined indications for treatment by categorizing men and women into mutually exclusive hierarchical groups. We used this approach to 1) distinguish treatment decisions made at the initial consultation from those based subsequently on laboratory test results and 2) exclude patients who would be treated for chlamydia anyway. This allowed us to determine the prevalence of chlamydia among patients treated for gonorrhea who would not, in the absence of co-treatment, be treated with an antimicrobial regimen effective against C. trachomatis. We considered that the following patients had other indications for chlamydia treatment: men with nongonococcal urethritis (C. trachomatis is the organism most commonly associated with this disorder [23]); women with mucopurulent cervicitis or PID (who are treated for several potential organisms, including C. trachomatis); and patients whose partners were diagnosed with chlamydia, nongonococcal urethritis, mucopurulent cervicitis, or PID. Next, we categorized men into six groups and women into five groups on the basis of treatment indication. We considered men to have treatment indications for chlamydia if they had 1) nongonococcal urethritis by Gram stain or 2) a sex partner with chlamydia, mucopurulent cervicitis, or PID. We considered the remaining men to have treatment indications for gonorrhea if they had 3) gram-negative intracellular diplococci, 4) a sex partner with gonorrhea, or 5) a positive gonorrhea culture. The final group comprised men 6) without treatment indications for either infection. We considered women to have treatment indications for chlamydia if they had 1) a sex partner with chlamydia or nongonococcal urethritis or 2) a clinical diagnosis of mucopurulent cervicitis or PID. We considered the remaining women to have treatment indications for gonorrhea if they had 3) a sex partner with gonorrhea or 4) a positive gonorrhea culture. The final group comprised women 5) without treatment indications for either infection. Statistical Analysis We compared characteristics of patients included in this analysis with those of patients enrolled in the original study. Chlamydia prevalence was determined for patients with laboratory-confirmed gonorrhea and for patients with each of the hierarchical treatment indications. For comparison between groups, we used chi-square tests and relative risks (RRs) with 95% CIs. MantelHaenszel weighted RRs were used to calculate summary RRs for stratified analyses, for which GreenlandRobins confidence limits were calculated. The large-sample population proportion method (24) was used to calculate 95% CIs for prevalences. Role of the Funding Source Project RESPECT was supported by CDC cooperative agreements. Chlamydia PCR kits were donated by Roche Pharmaceuticals, which was not involved in study design, conduct, analysis, or interpretation. Results Study Participants Of the 4328 patients enrolled in Project RESPECT, 443 were excluded from this analysis because they did not have conclusive results from both a gonorrhea culture and a chlamydia PCR. The remaining 3885 patients (90%), 2184 men and 1701 women, were included. Our sample was similar to the sample in the original study and to the clinic populations in that patients were young (median age, 25 years), were members of racial or ethnic minority groups (59% black, 16% Hispanic, 20% white, and 6% other), had low income (<

Feasibility and yield of screening Urine for Chlamydia trachomatis by polymerase chain reaction among high-risk male youth in field-based and other nonclinic settings : A new strategy for sexually transmitted disease control

5000/y in 43%), and were approximately equally distribute

A Comparison of Single-Dose Cefixime with Ceftriaxone as Treatment for Uncomplicated Gonorrhea

Background: Inner‐city youth are at disproportionate risk for Chlamydia trachomatis infection. Identification of infected individuals is hampered by the often asymptomatic nature of infection and access and utilization barriers to clinic‐based screening services. The feasibility and yield of screening urine for C. trachomatis by polymerase chain reaction was studied among high‐risk male youth outside traditional clinic settings. Methods: As part of a community‐level sexually transmitted disease (STD) prevention program among high‐risk youth in Denver, outreach workers enrolled subjects, administered questionnaires, and collected first‐catch urine samples in nonclinical facility‐based and field‐based settings. Facility settings consisted of community/recreation centers, high‐schools, and an STD/human immunodeficiency virus prevention storefront. Field settings included alleys, parking lots, parks, and residences. Individuals who tested C. trachomatis positive were contacted by program outreach workers and provided with standard treatment and partner notification services. Results: Over a 20‐month period, 486 urine specimens were collected, 32 (6.6%) of which were C. trachomatis positive. Rates were higher for subjects screened in the field than in facility settings (11.9% vs. 4.4%, P < 0.05). Subjects with chlamydial infection were more likely to have had vaginal intercourse in the previous 30 days (adjusted odds ratio: 2.9) and to have been recruited in field settings (adjusted odds ratio: 2.5). Of subjects with chlamydial infection, 31/32 (97%) were treated within a median of 8 days after urine collection. Conclusions: Urine chlamydial screening by polymerase chain reaction of sexually active male youth in nontraditional settings appears to be feasible and to provide yields similar to those reported in standard clinic settings. Evaluation of samples easily collected in nonclinic locations holds great promise as an additional strategy for the control of chlamydial infection and other STD among difficult‐to‐reach populations.

Evaluation of a Strand Displacement Amplification Assay (BD ProbeTec-SDA) for Detection of Neisseria gonorrhoeae in Urine Specimens

BACKGROUND Because of the widespread existence of Neisseria gonorrhoeae resistant to penicillin or tetracycline, ceftriaxone is now recommended for the treatment of gonorrhea. There is, however, a need for effective antibiotics that can be administered orally as an alternative to ceftriaxone, which requires intramuscular administration. Cefixime is an orally absorbed cephalosporin that is active against resistant gonococci and has pharmacokinetic activity suitable for single-dose administration. METHODS AND RESULTS In a randomized, unblinded multicenter study of 209 men and 124 women with uncomplicated gonorrhea, we compared three single-dose treatment regimens: 400 mg or 800 mg of cefixime, administered orally, and 250 mg of ceftriaxone administered intramuscularly. The overall cure rates were 96 percent for the 400-mg dose of cefixime (89 of 93 patients) (95 percent confidence interval, 93.5 percent to 97.8 percent); 98 percent for the 800-mg dose of cefixime (86 of 88 patients) (95 percent confidence interval, 94.6 percent to 100 percent); and 98 percent for ceftriaxone (92 of 94 patients) (95 percent confidence interval, 94.9 to 100 percent). The cure rates were similar in men and women, and pharyngeal infection was eradicated in 20 of 22 patients (91 percent). Thirty-nine percent of 303 pretreatment gonococcal isolates had one or more types of antimicrobial resistance; the efficacy of all three regimens was independent of the resistance pattern. Chlamydia trachomatis infection persisted in at least half the patients infected in each treatment group. All three regimens were well tolerated. CONCLUSIONS In the treatment of uncomplicated gonorrhea, a single dose of cefixime (400 or 800 mg) given orally appears to be as effective as the currently recommended regimen of ceftriaxone (250 mg given intramuscularly).

In Vitro Comparison of Cefoxitin, Cefamandole, Cephalexin, and Cephalothin

ABSTRACT The performance of a strand displacement amplification assay (the BDProbeTec-SDA assay) in detecting Neisseria gonorrhoeae in urine specimens was evaluated. When performed under stringent quality control conditions, the BDProbeTec-SDA assay is a sensitive, specific, and efficient method for the screening of large numbers of noninvasively obtained specimens. Because the predictive value of an assay is a function of the prevalence of the disease, culture confirmation is needed for samples with positive results from populations in which the prevalence of a disease is low or in situations in which false-positive results may have important medical, psychosocial, or medicolegal consequences.

A clinical isolate of Neisseria gonorrhoeae with in vitro resistance to erythromycin and decreased susceptibility to azithromycin.

The in vitro effect of cefoxitin, cefamandole, cephalexin, and cephalothin was tested against 645 strains of bacteria recently isolated from clinical sources. Against gram-positive organisms cephalothin and cefamandole were the most effective, generally being three- to fourfold more active than cephalexin or cefoxitin. Enterococci were not inhibited by less than 25 μg of any of the antibiotics per ml. Against Enterobacteriaceae, cefoxitin and cefamandole were the most active. An exception was the Enterobacter strains, against which cefoxitin was the least effective. None of the Pseudomonas aeruginosa strains were susceptible to 100 μg of any of the cephalosporins per ml. Cefamandole was the most active agent against Neisseria meningitidis and Neisseria gonorrhoeae. It was also the most effective agent against Haemophilus influenzae, even when taking into account a threefold inoculum effect.

In Vitro Activity of Netilmicin Compared with Gentamicin, Tobramycin, Amikacin, and Kanamycin

Background and Objectives: Erythromycin is a recommended treatment for penicillin‐allergic pregnant women with gonorrhea, and azithromycin has been suggested as therapy for coexisting gonococcal and chlamydial infections. Although gonococcal resistance to erythromycin is not uncommon, decreased resistance to azithromycin is rare. A clinical isolate of Neisseria gonorrhoeae with in vitro resistance to erythromycin and decreased susceptibility to azithromycin is reported. Study Design: This is a case report. Results: Antimicrobial susceptibility testing of a clinical isolate of N. gonorrhoeae revealed a minimal inhibitory concentration (MIC) of 2 μg/ml to azitthromycin and 32 μg/ml to erythromycin. Five hundred other urethral isolates were tested, resulting in an MIC for erythromycin ranging from 0.015 to 2 μg/ml. The range for azithromycin was 0.015 to 0.5 μg/ml. There was a strong correlation between erythromycin and azithromycin MICs (r = 0.73; P < 0.0001). Conclusions: Continued national monitoring is needed to detect the appearance and early dissemination of new types of gonococcal resistance.

Effects of Ampicillin-Amikacin and Ampicillin-Rifampin on Enterococci

The in vitro activity of netilmicin was compared with that of gentamicin, tobramycin, amikacin, and kanamycin against 636 strains of bacteria recently isolated from clinical sources. Gentamicin was the most active antibiotic, but netilmicin and tobramycin closely paralleled it. Netilmicin was generally four-to eightfold less active than gentamicin against Serratia and group A streptococci, and was twofold less active against Pseudomonas aeruginosa. When effects of inoculum size and concentration of divalent cations in the media were evaluated, netilmicin was shown to be similar to gentamicin in vitro. Minimum inhibitory concentrations for P. aeruginosa were increased as much as 18-fold when the Mg2+ and Ca2+ concentrations were increased to physiological levels in Mueller-Hinton broth.

Quinolone-resistant Neisseria gonorrhoeae : The beginning of the end? Report of quinolone-resistant isolates and surveillance in the southwestern United States, 1989 to 1997

Fifty-seven clinical isolates of enterococcus were tested for susceptibility to 10 antibiotics in a microtiter broth dilution system. Amoxicillin, ampicillin, vancomycin, and rifampin inhibited all strains at concentrations easily achievable in blood. Resistance to rifampin developed rapidly. Of the aminoglycosides, gentamicin was most active, followed in decreasing order by tobramycin, amikacin, kanamycin, and streptomycin. High-level resistance to streptomycin was present in 26% of the strains and to kanamycin in 23% of the strains. Growth curve studies of selected strains revealed synergy with ampicillin-amikacin and antagonism with ampicillin-rifampin. It is suggested that ampicillin-gentamicin constitutes adequate initial therapy for enterococcal infections until the results of tests for high-level resistance to kanamycin and streptomycin are known and that clinical trails of ampicillin-amikacin are warranted.