Comparison of secular trends in pneumococcal serotypes causing invasive disease in Denver, Colorado (1971-2004) and serotype coverage by marketed pneumococcal vaccines.

Invasive pneumococcal isolates from three hospitals in Denver, CO, USA were serotyped between 1971 and 2004. Serotype 14 was most common (13.2%), and other prevalent serotypes (3, 4, 6, 9 and 19) together accounted for 44.1% of the isolates. All prevalent serotypes and 91.3% of the total isolates were covered by pneumococcal polysaccharide vaccine, while 79.1% of prevalent serotypes and 56.7% of total isolates were covered by pneumococcal conjugate vaccine. Serotypes 6, 9 and 14 were more common in the final decade than in the first decade studied (37.3% vs. 20.2%), whereas serotypes 3 and 23 were more common in the first decade (18.5% vs. 11.0%).

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

BACKGROUND: Fluoroquinolones are one of the most widely used treatments for gonorrhoeae. Changes in the susceptibility of Neisseria gonorrhoeae to these agents may threaten their use. GOAL OF THIS STUDY: To report several resistant strains (>1 mcg/ml) isolated in the western United States and to evaluate the prevalence of strains with reduced susceptibility (ofloxacin 0.25 mcg/ml, ciprofloxacin 0.06 mcg/ml). STUDY DESIGN: The microbiology and epidemiology of three resistant strains were characterized and 12,761 other strains were evaluated for fluoroquinolone susceptibility as part of the Gonococcal Isolate Surveillance Project of the Centers for Disease Control and Prevention. RESULTS: Fluoroquinolone-resistant strains may appear sporadically. The prevalence of isolates with reduced susceptibility to fluoroquinolones remains low in the Southwest region of the United States. CONCLUSIONS: Continued active surveillance is needed to detect and control the spread of quinolone-resistant Neisseria gonorrhoeae.

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.

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.

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

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 micrograms/ml to azithromycin and 32 micrograms/ml to erythromycin. Five hundred other urethral isolates were tested, resulting in an MIC for erythromycin ranging from 0.015 to 2 micrograms/ml. The range for azithromycin was 0.015 to 0.5 micrograms/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.

Evaluation of chlamydiazyme enzyme immunoassay for detection of Chlamydia trachomatis in urine specimens from men.

Paired first-voided urine and urethral swab specimens were collected from 540 men attending sexually transmitted disease clinics in three geographic locations. Urine specimens were tested for the presence of Chlamydia trachomatis by commercial enzyme immunoassay (Chlamydiazyme), and the results were compared with those of urethral swab cultures. Overall prevalence of urethral C. trachomatis by culture was 14%, and the Chlamydiazyme assay had an overall sensitivity of 83%, a specificity of 96%, a positive predictive value of 76%, and a negative predictive value of 97%. Sensitivity was greater (94%) in those culture-positive samples with a high antigen load (> or = 20 inclusion-forming units per coverslip) than those with a lower antigen load (68%). Assay of urine specimens from men attending sexually transmitted disease clinics by Chlamydiazyme appears to be a reliable, noninvasive method of detection of C. trachomatis infection, and further evaluation of its performance in asymptomatic and low-prevalence populations is indicated.

A comparison of single-dose cefixime with ceftriaxone as treatment for uncomplicated gonorrhea. The Gonorrhea Treatment Study Group.

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).

Unsuspected Chlamydia trachomatis infection in heterosexual men attending a sexually transmitted diseases clinic: evaluation of risk factors and screening methods.

To characterize the problem of unsuspected Chlamydia trachomatis infection in heterosexual men attending a sexually transmitted diseases (STD) clinic, the authors assessed risk factors for infection and the value of screening for infection by gram-stained smears and urinalysis in 438 men who did not have conventional clinical indications for chlamydial treatment at their initial visit. Evaluations included urethral swabs for gram-stained smears and Neisseria gonorrhoeae and C. trachomatis cultures and microscopy of first-catch urine sediment. C. trachomatis was isolated from 29 subjects (6.6%) and N. gonorrhoeae from 6 subjects (1.3%), (P less than .05). The only demographic or clinical factors that were associated with C. trachomatis were age younger than 21 years and five or more lifetime sexual partners. Screening for C. trachomatis with urethral gram stain and urine sediment examination had sensitivities of only 23% and 35%, respectively. Risk factor assessment and screening with standard microscopic procedures do not adequately predict infection in this group, which accounts for almost 25% of the C. trachomatis burden in heterosexual men who visit an STD clinic. More specific chlamydia detection methods are needed for effective control programs.

Genital Chlamydia infections.

The past decade has seen a breakthrough in laboratory methods for the diagnosis of chlamydial infections. Antigen detection methods have made screening for C. trachomatis available in most clinical laboratories. These methods are highlighted and evaluated. Current culture methods and the antibiotic susceptibility of C. trachomatis are also discussed.

Gonorrhea.

Laboratory methods for the isolation and identification of Neisseria gonorrhoeae are updated. The antimicrobial susceptibility patterns of the gonococcus are changing and becoming less predictable. Methods for monitoring susceptibility are presented. The use of serotyping, auxotyping, and molecular techniques to characterize gonococcal isolates and the epidemiological applications are reviewed.

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.

Factors related to genital Chlamydia trachomatis and its diagnosis by culture in a sexually transmitted disease clinic.

The authors cultured 2,320 patients who attended the Denver Metro Health Clinic for Sexually Transmitted Diseases from September 1981 to June 1983 to determine clinical and epidemiologic factors associated with genital chlamydial infection. Among consecutive heterosexual men with urethral discharge, 226 of 849 (27%) had positive urethral cultures, with rates significantly lower among those with profuse (18%) or purulent (19%) discharges, and higher (37%) among those with symptoms for more than seven days. In a subgroup of men without gonococci, those who had polymorphonuclear leukocytes on smear had higher isolation rates (33%) than those who did not (3%). Among consecutive female patients, 172 of 1,031 (17%) had positive cervical cultures, with rates significantly lower in those who were white (13%), married (7%), or using a diaphragm (0 of 77), and higher in those who were positive for Neisseria gonorrhoeae (38%). There was a marginally significant increased rate of chlamydial isolation among oral contraceptive users only for women aged 20 years or younger. Younger age was significantly associated with chlamydial isolation in both men and women after controlling for sexual activity and other factors. Various patient characteristics can be combined to define subgroups of men and women, with rates of isolation ranging from under 4% to over 60%. These results can be useful in deciding whom to test and whom to treat presumptively in a public health setting.

PIP: To increase knowledge of the prevalence of genital chlamydia trachomatis infection and the associated epidemiologic and clinical factors, cultures were obtained from 2320 patients at a Denver clinic for sexually transmitted diseases. Specific subsamples examined included 96 consecutive male clinic attendees with no urethral discharge on examination, 1193 consecutive male attendees with urethral discharge, and 1031 consecutive female attendees. Only 4 (4%) of the men attending the clinic who did not have a discharge on examination were positive for chlamydial infection compared with 275 (23%) of men with a discharge. Of the men with discharge, the isolation rate of chlamydia was 27% among heterosexuals but only 14% among homosexuals and bisexuals. Of the female attendees cultured, 172 (17%) had positive cervical findings. Younger age was associated with chlamydial infection in both men and women even after controlling for sexual activity. In a subgroup of men without gonococci, those who had polymorphonuclear leukocytes on smear had higher isolation rates (33%) than those who did not (3%). Among women, chlamydia rates were significantly lower for whites (13%), married women (7%), and diaphragm users (0%). There was a marginally significant increased rate of chlamydial isolation among oral contraceptive users only for women aged 20 years or below. Significantly fewer (18%) men with profuse discharge were positive for chlamydial infection compared with men with a scant or moderate discharge (27% and 31%, respectively), and those with a purulent discharge were less likely to be positive than men with a clear or white discharge. Stepwise multiple logistic regression suggested the following risk factors for chlamydial infection in men: polymorphonuclear leukocytes, gram-stained smear negative for intracellular diplococci, age under 25 years, history of discharge, discharge for more than 7 days, and no dysuria. Risk factors for women included age less than 25 years, unmarried status, gonorrhea, an abnormal cervix, pelvic inflammatory disease, and no recent antibiotic use.

Activity of nonoxynol-9 against Chlamydia trachomatis.

PIP: An analysis of in vitro research aimed at determining the effect of nonoxynol-9 against Chlamydia trachomatis concludes that clinical research is needed to resolve the issue. There are 3 reports that the spermicide killed Chlamydia. All used iodine stain, which detects glycogen, and fails to demonstrate immature organisms without inclusion bodies. The study that used a species specific fluorescent marker for Chlamydia membranes found no effect even with 50% spermicide. Another problem is cytotoxicity for the tissue culture cells used in the assay, which appears to be common even at low concentrations of nonoxynol-9. The timing of the inoculation of Chlamydia into the experimental cultures also appeared to affect the results differentially. It appears that controlled clinical trials will be needed to resolve this issue.^ieng

Treatment of uncomplicated gonorrhea with single-dose imipenem-cilastatin.

Single 500-mg intramuscular doses of imipenem-cilastatin cured 116 (95%) of 122 men and 9 of 9 women with uncomplicated gonorrhea due to beta-lactamase-negative Neisseria gonorrhoeae. Most co-existing Chlamydia trachomatis infections persisted. Imipenem-cilastatin is effective for uncomplicated gonorrhea in men but has no advantages over other available regimens.

Fluorescent monoclonal antibody for confirmation of Neisseria gonorrhoeae cultures.

We evaluated a monoclonal fluorescent-antibody (FA) reagent (Neisseria gonorrhoeae Culture Confirmation Test; Syva Co., Palo Alto, Calif.) for confirmation of N. gonorrhoeae isolates obtained from clinics for sexually transmitted diseases in four cities. The FA test was performed in parallel with established confirmation procedures on all organisms growing on 773 primary culture plates of modified Thayer-Martin agar. All N. gonorrhoeae isolates reacted with the FA reagent and produced a bright, easily interpretable fluorescence. The FA test correctly identified 533 N. gonorrhoeae isolates from 474 patients and did not react with 90 N. meningitidis or with 213 non-Neisseria isolates. In one city (Baltimore), Gonochek II (Du Pont Co., Wilmington, Del.) failed to identify four N. gonorrhoeae isolates reactive with the FA reagent and confirmed as N. gonorrhoeae by Phadebact (Pharmacia Inc., Piscataway, N.J.) and acid production from sugars. The FA test was rapid and specific and could be performed directly from primary isolation plates. The test requires 1 h to perform and is applicable to mixed-flora cultures.

Auxotype/serovar diversity and antimicrobial resistance of Neisseria gonorrhoeae in two mid-sized American cities.

To characterize the prevalence and heterogeneity of Neisseria gonorrhoeae with chromosomally mediated resistance to penicillin G or tetracycline.HCl in Seattle, Washington, and Denver, Colorado, we auxotyped, serotyped, and determined the MICs of penicillin G and tetracycline for gonococcal isolates collected in both cities during 1984. In Seattle 37 (18%) and ten (5%) of 205 isolates had MICs for penicillin G of greater than or equal to 1.0 and greater than or equal to 2.0 micrograms/ml, respectively; in Denver eight (3%) of 240 isolates had MICs for penicillin of 1.0 microgram/ml, and none had MICs of greater than 1.0 microgram/ml. For tetracycline.HCl, 107 (52%) and 38 (19%) of Seattle isolates had MICs of greater than or equal to 1.0 and greater than or equal to 2.0 micrograms/ml, respectively, while in Denver the respective figures were 111 (46%) and 48 (20%). In each city, antimicrobial resistance was present in a number of auxotype/serovar (A/S) classes: isolates with MICs for penicillin G of greater than or equal to 1.0 microgram/ml were identified in 15 of 49 A/S classes in Seattle and in five of 49 A/S classes in Denver. These data indicate that chromosomal resistance to penicillin G and tetracycline.HCl varies geographically in prevalence and is a heterogeneous phenomenon involving multiple gonococcal strains.

Comparative study of cefoperazone and spectinomycin for treatment of uncomplicated gonorrhea in men.

Beta-lactamase-negative Neisseria gonorrhoeae infections were treated with single-dose cefoperazone (0.5 or 1.0 g) or spectinomycin (2.0 g). Anogenital infections were cured in 36 (83%) of 43 volunteers given 0.5 g of cefoperazone, 61 of 61 volunteers given 1.0 g of cefoperazone, and 99 of 100 volunteers given spectinomycin. The cefoperazone geometric mean MIC for 242 isolates was 0.028 microgram/ml. Cefoperazone (1.0 g) and spectinomycin (2.0 g) are comparable for the therapy of anogenital gonorrhea in men.

Comparative study of ceftriaxone and spectinomycin for treatment of pharyngeal and anorectal gonorrhea.

Of the currently recommended regimens for treatment of uncomplicated gonorrhea, only aqueous penicillin G procaine is effective against infections at all sites. However, procaine penicillin is not effective against penicillinase-producing Neisseria gonorrhoeae and suffers from poor patient acceptability owing to the 10-mL volume of injection and allergic and toxic procaine reactions. Ceftriaxone is a new extended-spectrum cephalosporin with a long serum half-life and is many times more active than penicillin G against both beta-lactamase-positive or -negative strains of N gonorrhoeae. Ceftriaxone was compared as a single, 125-mg, 0.5-mL injection with a single 2-g injection of spectinomycin in difficult to treat pharyngeal gonorrhea in men and women and anorectal gonorrhea of men. Ceftriaxone cured 30/32 (94%) pharyngeal and 52/52 anorectal infections, compared with 6/14 (43%) and 9/9, respectively, for spectinomycin. Both regimens were well tolerated. Ceftriaxone may prove to be a drug of choice for uncomplicated gonorrhea, particularly where homosexual men are treated and/or penicillinase-producing N gonorrhoeae is prevalent.