Mark G. Martens

Clinical validation of the Cervista® HPV HR and 16/18 genotyping tests for use in women with ASC-US cytology

OBJECTIVEnHigh-risk (HR) human papillomavirus (HPV) testing is important in cervical cancer screening for triage to colposcopy. This study evaluated the clinical performance of the Cervista HPV HR and 16/18 genotyping tests for detection of HPV in cervical cytology specimens.nnnMETHODSnThe tests were prospectively evaluated in a multicenter clinical study. DNA was extracted from approximately 4000 residual liquid-based cytology specimens collected during routine liquid-based Papanicolaou tests at standard of care visits and was assessed for the presence of HR HPV and/or HPV types 16 and 18. All women with cytology results of atypical squamous cells of undetermined significance (ASC-US) or greater underwent colposcopic examination and biopsies were collected. Test results were compared with local colposcopy and histology results from a central pathology review panel.nnnRESULTSnThere were 1347 subjects with complete data sets of cytology, HR HPV, colposcopy, and histology included in the analysis of the HPV HR test. Sensitivity of the HPV HR test for detection of cervical intraepithelial neoplasia (CIN) 2+ among women with ASC-US cytology was 92.8% (95% confidence interval [CI]: 84.1-96.9) and the negative predictive value (NPV) was 99.1% (95% CI: 98.1-99.6). Sensitivity for detection of > or =CIN 3 in women with ASC-US was 100% (95% CI: 85.1-100) and the NPV was 100% (95% CI: 99.4-100). The specificity of the test for detection of > or =CIN 2 and > or =CIN 3 was 44.2% (95% CI: 41.5-46.9) and 43% (95% CI: 40.3-45.7), respectively. The HPV 16/18 genotyping test also performed as expected in women with ASC-US cytology who were positive for HR HPV.nnnCONCLUSIONnThe Cervista HPV HR test can be clinically used for detecting HR HPV types in conjunction with cervical cytology for use in triage of women with ASC-US cytology during routine cervical cancer screening.

Antibiotic prophylaxis: Is there a difference?

Seven antibiotics, administered in 10 different regimens for prophylaxis, were randomly assigned to 1580 patients who were delivered by cesarean section. Cefazolin 1 gm, administered for three doses, served as the control group. Cefazolin 1 gm, cefazolin 2 gm, cefoxitin 1 gm, cefoxitin 2 gm, cefonicid 1 gm, cefotetan 1 gm, ceftizoxime 1 gm, ampicillin 2 gm, and piperacillin 4 gm were all administered in a single dose. Four antibiotics proved to be superior in preventing postpartum endometritis: ampicillin 2 gm (p = 0.03), cefazolin 2 gm (p = 0.005), piperacillin 4 gm (p = 0.0007), and cefotetan 1 gm (p = 0.0001). Single-dose cephalosporin antibiotic prophylaxis was found to result in approximately a twofold increase in Enterococcus faecalis colonization of the vagina (p less than 0.01). This may be significant in patients in whom postpartum endometritis develops and who have failure of initial treatment with a broad-spectrum cephalosporin, e.g., cefoxitin or cefotetan, or a combination such as clindamycin or metronidazole plus an aminoglycoside. Rupture of amniotic membranes for a half hour or more was associated with an increased risk for postpartum endometritis. The use of internal fetal monitoring was associated with an increased risk of soft tissue pelvic infection.

Vaginal flora and pelvic inflammatory disease

Forty-one patients with acute pelvic inflammatory disease were evaluated for the coexistence of bacterial vaginosis. Because all patients had a copious purulent vaginal discharge, microscopic criteria could not be used and microbiologic criteria were employed. The vaginal bacterial flora were not consistent with that of bacterial vaginosis, because Lactobacillus and other gram-positive bacteria dominated with colony counts of 10(3) to 10(5) cfu/ml (colony-forming units per milliliter). Endocervical specimens yielded Neisseria gonorrhoeae from 20 patients and Chlamydia trachomatis from 11 patients. Anaerobes were not dominant in any site sampled. A total of 147 bacteria were isolated from the endometrium, 16 (11%) of which were anaerobes. Thus the endogenous bacterial flora were not consistent with that of the microbiologic definition of bacterial vaginosis. N. gonorrhoeae was the most common isolate from the endocervix and endometrium; it was isolated three times more frequently from the endocervix and two times more frequently from the endometrium than was C. trachomatis.

Comparative evaluation of three TactylonTM condoms and a latex condom during vaginal intercourse: breakage and slippage

This study compared breakage and slippage rates of three male condom styles made of Tactylon(TM), a synthetic elastomer, to those of a marketed latex condom during vaginal intercourse. Safety and acceptability outcomes were also assessed. This two-center, prospective, crossover study enrolled 443 couples. Each couple was randomly assigned to use three condoms of each type in one of 24 use sequences. Couples completed questionnaires after using each condom, all of one condom type, and all four condom types. The percentage and standard error (SE, in parentheses) of latex condoms with clinical breakage was 0.86% (0.295). Percentages for Tactylon condoms were not equivalent to the latex study condom, ranging from 3.50% to 4.17%. The percentage and SE of latex condoms with complete slippage was 1.11% (0.328). Percentages for Tactylon condoms were equivalent to those for latex, ranging from 0.70% to 1.31%. The Low-Modulus Tactylon condom was the most preferred. Fewer medical events were reported with the Tactylon condoms than with the latex condom. It was concluded that Tactylon condoms were equivalent to the latex condom in terms of slippage but not breakage. However, safety and acceptability seemed to be better for Tactylon condoms. This may improve consistency of use and may attract new users.

Imiquimod 3.75% Cream Applied Daily to Treat Anogenital Warts: Combined Results from Women in Two Randomized, Placebo-Controlled Studies

Objective. To evaluate if new imiquimod formulations using a shorter treatment duration are safe and efficacious to treat anogenital warts. Methods. In two studies 534 women ≥12 years of age (mean 33.4) with 2–30 warts (mean 7.9) and total wart area ≥10u2009mm2 (mean 166.3) were randomized (1u2009:u20092u2009:u20092) to placebo (106), imiquimod 2.5% (212) or 3.75% (216) creams applied once daily until complete clearance or a maximum of 8 weeks. Results. For placebo, imiquimod 2.5% and 3.75%, respectively, complete clearance of all warts was achieved in 14.2%, 28.3%, and 36.6% of women (intent-to-treat, P = 0.008 imiquimod 2.5%, and P < 0.001 3.75% versus placebo). Mean changes in wart counts were −10.7%, −50.9%, and −63.5% (per-protocol, P < 0.001 each active versus placebo) and safety-related discontinuation rates 0.9%, 1.4%, and 2.3%. Conclusions. Imiquimod 3.75% applied daily for up to 8 weeks was well tolerated and superior to placebo in treating women with external anogenital warts.

Concerns regarding the centers for disease control's published guidelines for pelvic inflammatory disease

The International-Infectious Disease Society for Obstetrics and Gynecology-USA (I-IDSOG-USA) has concerns about the most recently published Centers for Disease Control and Prevention (CDC) guidelines for pelvic inflammatory disease (PID). I-IDSOG-USA advocates the following changes when the guidelines are revised. We recommend the use of the term upper genital tract infection (UGTI), followed by the designation of the etiologic agent, instead of the currently employed term, pelvic inflammatory disease, or PID. In diagnoses, there should be greater emphasis on signs and symptoms related to subclinical or occult UGTI. Therapeutic recommendation for the treatment of UGTI should be documented for various stages of this diverse disease entity. There should be greater emphasis on hospitalization for infected nulligravida teenagers. This permits monitoring of antibiotic treatment and provides a site for medical educational efforts to teach this medically underserved segment of our society how to protect their future fertility, their health, and their lives.

Gestational pyelonephritis - associated Escherichia coli isolates represent a nonrandom, closely related population

OBJECTIVEnA select group of Escherichia coli strains known as uropathogenic cause pyelonephritis in nonpregnant individuals. We investigated whether Escherichia coli from gestational pyelonephritis represent a random population or possess common uropathogenic characteristics.nnnSTUDY DESIGNnRepetitive element sequence-based polymerase chain reaction, plasmid profiles, hemolysin, and O serotypes were assayed from Escherichia coli isolates of 57 pregnant patients with acute pyelonephritis at different gestational ages.nnnRESULTSnThe majority of the first trimester isolates fell primarily into repetitive element sequence-based patterns 1 and 3 and O6, O15, and O75 serotypes. Second-trimester isolates had multiple patterns with high-frequency repetitive element sequence-based polymerase chain reaction 1 and 5 and an unknown (OX) serotype. Pattern 3, predominantly O75 serotype, was found primarily among third-trimester isolates.nnnCONCLUSIONnIt is likely that Escherichia coli associated with acute pyelonephritis during different trimesters of pregnancy represents nonrandom closely related isolates, and some of these strains may be characteristic in pregnant patients only.

Susceptibility of female pelvic pathogens to oral antibiotic agents in patients who develop postpartum endometritis

Fifteen hundred patients were enrolled in a prospective, randomized study on the effect of antibiotic prophylaxis during cesarean section. Two hundred thirty-one patients developed postpartum endometritis, and the isolates obtained from the endometrium were tested for sensitivity to ampicillin, cefuroxime, ofloxacin, ciprofloxacin, and clindamycin. Minimum inhibitory concentrations of 50% and 90% of ampicillin, cefuroxime, and clindamycin were similar to previously reported values; however, slight differences were noted in the activity of the two quinolones to common pelvic isolates. The minimum inhibitory concentrations of 90% of ofloxacin and ciprofloxacin to 119 isolates of Enterococcus faecalis were 4.0 and 2.0, to 17 isolates of Staphylococcus aureus 1.0 and 0.5, to 39 isolates of Escherichia coli 0.5 and 1.0, to 46 isolates of Bacteroides bivius 4.0 and 8.0, to 57 isolates of Gardnerella vaginalis 1.0 and 2.0, to 71 isolates of Staphylococcus epidermidis 0.5 and 0.5, to 16 isolates of Proteus mirabilis 0.25 and 0.12, and to 50 isolates of Lactobacillus species 32.0 and 8.0 micrograms/ml, respectively. In summary, the quinolones have activity comparable with a variety of other oral agents versus female pelvic pathogens, with the quinolones ofloxacin and ciprofloxacin having better activity against most of the gram-negative isolates. Anaerobic activities were comparable with the beta-lactams, but inferior to clindamycin and metronidazole as expected.

Perspectives on the bacteriology of postoperative obstetric-gynecologic infections

The development of postoperative infections is influenced by both host and external factors. The present report focuses on the influence of prophylactic agents on the apparent cause of infection after cesarean section and vaginal hysterectomy. The correlation between in vitro susceptibility patterns of potential pathogens and normal flora and in vivo response is also considered.

Treatment of acute gynecologic infections with trovafloxacin

BACKGROUNDnTrovafloxacin, a broad-spectrum fourth-generation quinolone with gram-positive and gram-negative aerobic and anaerobic bacterial activity, is available in oral and intravenous formulations. The objective of this prospective, multicenter, double-blind, randomized study was to compare the efficacy of trovafloxacin with that of cefoxitin, an approved drug for treatment of acute gynecologic infections, together with amoxicillin/clavulanic acid as oral follow-on treatment.nnnMETHODSnPatients with a clinical diagnosis of acute pelvic infection received either intravenous alatrofloxacin with oral trovafloxacin follow-on (trovafloxacin) or a combined regimen of cefoxitin followed by amoxicillin/clavulanic acid for a maximum of 14 days. The primary endpoint was clinical response to therapy on follow-up at day 30.nnnRESULTSnClinical success rates were comparable between the trovafloxacin (n = 107) and comparative (n = 119) groups at study end (90% vs. 86%, respectively; 95% confidence interval, -4.5, 12.5). Among clinically evaluable patients, clinical success rates for infections involving Enterococcus species were higher with trovafloxacin than with the comparative regimen at the end of treatment (96% and 85%) and at study end (96% and 86%).nnnCONCLUSIONnIntravenous alatrofloxacin followed by oral trovafloxacin for a maximum of 14 days of total therapy was efficacious in the treatment of acute pelvic infections.