Virulence factors of Escherichia coli isolated from female reproductive tract infections and neonatal sepsis.

OBJECTIVE: The presence of enterobacteria such as Escherichia coli in the vagina of normal women is not synonymous with infection. However, vaginal E. coli may also cause symptomatic infections. We examined bacterial virulence properties that may promote symptomatic female reproductive tract infections (RTI) and neonatal sepsis. METHODS: E. coli isolated as the causative agent from cases of vaginitis (n = 50), tubo-ovarian abscess (n = 45) and neonatal sepsis (n = 45) was examined for selected phenotypic and genetic virulence properties. Results were compared with the frequency of the same properties among fecal E. coli not associated with disease. RESULTS: A significantly greater proportion of infection E. coli exhibited D-mannose resistant hemagglutination compared with fecal E. coli (p < 0.01). This adherence phenotype was associated with the presence of P fimbriae (pap) genes which were also significantly more prevalent among isolates from all three infection sites (p < 0.01). The majority of pap+ isolates contained the papG3 allele (Class II) regardless of infection type. Increased frequency of Type IC genes among vaginitis and abscess isolates was also noted. No significant differences in frequency of other bacterial adherence genes, fim, sfa, uca (gaf or dra were observed. E. coli associated with vaginitis was significantly more likely to be hemolytic (Hly+) than were fecal isolates (p < 0.05). The Hly+ phenotype was also more prevalent among tubo-ovarian abscess and neonatal sepsis isolates (p < 0.08). CONCLUSIONS: E. coli isolated from female RTI and neonatal sepses possess unique properties that may enhance their virulence. These properties are similar to those associated with other E. coli extra-intestinal infections, indicating that strategies such as vaccination or bacterial interference that may be developed against urinary tract infections (UTI) and other E. coli extra-intestinal infections may also prevent selected female RTI.

Vulvar hypertrophy with lymphedema. A mimicker of aggressive angiomyxoma.

We report the case of a 43-year-old quadriplegic woman with bilateral vulvar enlargement. The clinical impression was labial hypertrophy, but the microscopic features mimicked aggressive angiomyxoma because of the location, hypocellular proliferation of fibroblastic cells in an edematous-myxoid stroma, and vessels with perivascular collagen deposition, which simulated the thick-walled vessels of aggressive angiomyxoma. Since the lesion lacked true thick-walled vessels and contained ectatic tortuous lymphatics, the pathologic interpretation was lymphedema. This vulvar lesion should be recognized to prevent the misdiagnosis of aggressive angiomyxoma.

Excess intrauterine fetal demise associated with maternal human immunodeficiency virus infection.

A prospective study of transplacental transmission of human immunodeficiency virus (HIV) showed an increased rate of spontaneous fetal demise in HIV-seropositive mothers: 14 losses in 124 pregnancies. HIV was detected in placental and fetal tissues in 7 of 14 by in situ hybridization. The proportion of fetal infection far exceeded the transmission rate of 13% in liveborn babies. No association was seen between fetal transmission and a maternal history of drug abuse or coinfections; mothers with AIDS more often had fetal loss associated with HIV transmission than did asymptomatic mothers. In affected fetuses, HIV was detected in many tissues and was associated with thymic pathology. This suggests that maternal HIV infection increases the risk for pregnancy loss associated with HIV transmission. The possibility that HIV may be fetotoxic, that thymic dysfunction may interfere with pregnancy progression, or that the intrauterine milieu in HIV-seropositive pregnancies may be unfavorable (or a combination of factors) should be considered.

Association between anti-human immunodeficiency virus type 1 (HIV-1) antibody-dependent cellular cytotoxicity antibody titers at birth and vertical transmission of HIV-1.

Because vertical transmission of human immunodeficiency virus type 1 (HIV-1) from mother to infant occurs in only 15%-35% of possible opportunities, natural immune defenses of the mother, fetus, or neonate may be protective against infection. The relation between antibody-dependent cellular cytotoxicity (ADCC) antibodies and HIV-1 infection was explored in 78 neonates born to HIV-infected women. More than 90% of sera had measurable ADCC titers against HIV-1IIIB. Infant titers were closely correlated with maternal titers but were independent of total IgG and total antibody reactive to the same strain in whole virus ELISA. At birth, mean ADCC antibody levels of infants or their mothers were the same for infants who were infected and those who ultimately seroreverted and remained healthy. ADCC antibody titers against HIV-1SF2 were weakly correlated with anti-HIV-1IIIB titers and did not predict protection from HIV-1 infection. High levels of anti-HIV-1 ADCC antibody at birth are not protective against vertical transmission of HIV-1.

Prevalence of beta-lactamase enzyme production in bacteria isolated from women with postpartum endometritis.

One hundred eighty-four postpartum patients with the diagnosis of endomyometritis underwent intrauterine culturing. Beta-Lactamase production was tested using nitrocephin-impregnated discs in 278 bacterial isolates from patients with postpartum endometritis. beta-Lactamase production was found to be present in 149 of 278 (54%) isolates tested: 0 of 39 Streptococcus faecalis (0%), 22 of 41 Escherichia coli (54%), 66 of 68 Bacteroides bivius (97%), 0 of 13 Proteus mirabilis (0%) and 15 of 42 Staphylococcus epidermidis (36%). Anaerobes, as a group, had the highest rate of beta-lactamase production, 94 of 102 (93%), followed by gram negatives, 34 of 84 (40%), then gram positives, 21 of 91 (23%). However, it was the beta-lactamase produced by the gram-negative bacteria that was most responsive to the addition of a beta-lactamase inhibitor. The frequent isolation of beta-lactamase-producing bacteria from patients with postpartum endometritis raises concern about the use of antibiotics not resistant to these enzymes. Therefore, antibiotics combined with a beta-lactamase inhibitor may have potential as single-agent therapy in obstetric and gynecologic infections.

Contraception and sexually transmitted diseases: interactions and opportunities.

Today "safe sex" means protection from both unintended pregnancy and sexually transmitted disease and human immunodeficiency virus. These parallel complications of sexual activity have serious biologic and clinical sequelae that should be considered at the time of contraceptive selection. In addition, there is ongoing debate regarding potential interactions between antibiotic intervention and contraceptive steroids. This article assesses the impact of hormonal contraception, spermicides, barrier methods, intrauterine devices, and douching on the pathogenesis of sexually transmitted disease and the human immunodeficiency virus infection. It discusses the direct and indirect effects of contraception methods on clinical physiology and host immune responses while also considering the possible consequences on maternal and infant health if pregnancy results from the use of ineffective contraception. Counseling and care for both family planning and infectious disease protection must be provided to all sexually active individuals.

PIP: The notion of safe sex currently denotes protection from unintended pregnancy, HIV, and other sexually transmitted diseases (STD). Modern parallel complications of sexual activity should therefore be considered when selecting contraceptives. This article assesses the impact of hormonal contraception, spermicides. barrier methods, IUDs, and douching on the pathogenesis of STDs and HIV. It discusses the direct and indirect effects of contraception methods on clinical physiology and host immune responses while considering the possible consequences on maternal and infant health if pregnancy results from the use of ineffective contraception. It is concluded that significant interactions exist between forms of contraception and STDs and HIV which may be beneficial or harmful to women. For example, oral contraceptive (OC) use may reduce risks of pelvic inflammatory disease and its sequelae, but may increase risks of chlamydia infection. Barrier methods, especially when combines with spermicides, can reduce the risk of STDs/HIV if used consistently. The combined use of OCs and condoms offers serious defense against both unintended pregnancy and STDs/HIV. IUDs also seem safe and effective in women at low risk for reproductive tract infection. Periodic screening and treatment for prevalent STDs and possible bacterial vaginosis can protect the health of individuals and their sexual contacts. Finally, more research is needed on the reproductive and infectious disease repercussions of human sexuality, while counseling and care for family planning and infectious disease protection are recommended for those who are sexually active.

Ciprofloxacin versus gentamicin/clindamycin for postpartum endometritis.

An open, randomized, comparative study of intravenous ciprofloxacin versus gentamicin and clindamycin was performed on women with postpartum endometritis. Ciprofloxacin alone successfully eradicated the infections in 35 of 49 patients (71%), while the combination of gentamicin/clindamycin cured 41 of 48 (85%) (P = .15). The microbiology and antibiotic sensitivity of the endometrial isolates confirmed the poor activity of ciprofloxacin against anaerobic bacteria and less-than-optimal activity against Streptococcus faecalis. Ciprofloxacin, when used alone, may not be suitable for the treatment of postpartum endometritis.

Ticarcillin/clavulanate for treatment of postpartum endometritis.

Postpartum endometritis continues to be the leading cause of morbidity following cesarean section. This infection is commonly polymicrobial, involving aerobic, facultative, and obligate anaerobic gram-negative bacteria as well as gram-positive bacteria. The major risk factor for the development of post-cesarean section endometritis is duration of labor with ruptured amniotic membranes of greater than 6 hours. The most frequently utilized antibiotic regimen employed for treatment of postpartum endometritis is the combination of clindamycin and gentamicin. The combination ticarcillin/clavulanate has a spectrum of activity resembling that of clindamycin and gentamicin. In the data reported, cure rates among patients treated with ticarcillin/clavulanate were similar to the rates for those treated with clindamycin plus gentamicin as well as those for cefoxitin.

Effectiveness of ofloxacin in the treatment of Chlamydia trachomatis and Neisseria gonorrhoeae cervical infection.

Forty patients with cervical infection caused by Chlamydia trachomatis were treated with ofloxacin (20) or doxycycline (20). Ofloxacin was successful in eradicating C. trachomatis from all 20 (100%) patients. Doxycycline was effective in 18 of 20 (90%) patients. Three patients had a concomitant cervical gonococcal infection. All three were successfully treated: one with ofloxacin and two with doxycycline. Ofloxacin, 300 mg, taken twice daily for 7 days, is effective in eradicating endocervical C. trachomatis infection.

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.

Bacteriologic findings of post-cesarean endometritis in adolescents.

Two hundred four post-cesarean adolescents were compared with 751 adults to determine whether age was a risk factor for endometritis. Adolescents had an infection rate of 23%, compared with 11% for controls (P less than .001). Length of labor, duration of ruptured membranes, and the use of an internal monitor were noted to be risk factors for endometritis in adults, but not in adolescents. Endometrial aspirates from adolescents exhibited significantly higher isolation rates of Chlamydia trachomatis (21 versus 6%, P less than .05) and Gardnerella vaginalis (32 versus 9%, P less than .005) than did those from adults. Antepartum isolation of these organisms in teenagers may help to identify those at risk for postpartum endometritis.

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.

Ampicillin/sulbactam versus clindamycin in the treatment of postpartum endomyometritis.

Sixty-eight patients with postpartum endomyometritis were enrolled in this open randomized comparative study. Forty-two patients received ampicillin/sulbactam and 26 received clindamycin. The cure rates were similar in the two groups: 83% in the ampicillin/sulbactam group and 88% in the clindamycin group. The most frequent endometrial bacterial isolates were Bacteroides bivius, Streptococcus faecalis, Escherichia coli, and Ureaplasma urealyticum. Bacteremia was present in 15 of 68 (22%), the most frequent isolates being Mycoplasma (four cases) and B bivius (three cases). Clindamycin-resistant species were S faecalis, E coli, and Proteus mirabilis. There were seven treatment failures in the ampicillin/sulbactam group; only one isolate (an E coli) was resistant to ampicillin/sulbactam. In a significant number of these failures, Mycoplasma was isolated. Ampicillin/sulbactam and clindamycin were found to be equally efficacious in the treatment of postpartum endometritis.

Vaginitis.

This article is a review of the diagnosis and therapy of the common vaginal infections encountered by the clinician. The saline and wet mount preparations and vaginal pH are easy-to-use and effective means of establishing the correct diagnosis and should not be given until the patient has been examined and appropriate diagnostic tests carried out.

Trichomonas vaginalis.

Trichomonas vaginalis is one of the most common sexually transmitted diseases. The epidemiology, diagnosis, treatment, and concerns about transmission are discussed.

Transcervical uterine cultures with a new endometrial suction curette: a comparison of three sampling methods in postpartum endometritis.

The potential for cervicovaginal contamination has precluded direct sampling of the endometrial cavity and has led to the development of multi-lumen protected catheter systems, among other techniques. The extent of this presumed contamination was examined using three different techniques in 55 postpartum women with the diagnosis of endometritis. Each woman had the endometrium sampled with an unprotected cotton-tipped swab, a double-lumen catheter with brush, and a flexible endometrial suction curette. A statistically larger number of bacterial species was recovered with the cotton swab (2.4) than with the double-lumen catheter (1.3) or the suction curette (1.7) (P less than .001). A difference was also noted between the double-lumen catheter and the suction curette (P = .006); however, this represented less than one-third of a single bacterial species. The larger number of bacterial species recovered by the unprotected methods was found to result not from cervicovaginal contamination, as suspected, but from a significant increase in the recovery of bacteria commonly regarded as potential pathogens, such as Bacteroides bivius, Streptococcus faecalis, Proteus mirabilis, and Bacteroides melaninogenicus.

Sulbactam/ampicillin versus metronidazole/gentamicin in the treatment of post-cesarean section endometritis.

Sixty-seven patients diagnosed with post-cesarean-section endometritis were studied in a prospective comparative randomized trial of sulbactam/ampicillin, a new beta-lactamase inhibitor drug combination, versus treatment with metronidazole/gentamicin. The success rate was 91% for each antibiotic regimen. Mycoplasma spp. or Ureaplasma spp. were isolated from all treatment failures. Endometrial cultures revealed 2.3 aerobes as well as anaerobes per patient, with Enterococcus faecalis, Bacteroides bivius, and Escherichia coli the most frequently reported bacterial isolates in 64, 40, and 28% of all patients, respectively. Positive blood cultures were noted in 11 (15%) patients with Mycoplasma sp. the most commonly found isolate (45.5%). Sulbactam/ampicillin appears to be safe and equally effective as a metronidazole/aminoglycoside drug regimen in the treatment of postpartum endometritis.

Metronidazole, clindamycin, and quinolones.

This article covers well-known agents such as metronidazole that have decades of use for treatment of Trichomonas with newer applications in anaerobic diseases. Clindamycin, also used in treatment in anaerobic infections, is reassessed for its efficacy in treating vaginal infections and possibly with Chlamydia. Quinolones, a new group of agents with their applications in female genital tract and urinary tract infections is reviewed. Specific consideration is given to toxicity of these agents for the practicing obstetrician.

Normal vaginal flora in relation to vaginitis.

The normal vaginal, or resident, flora is complex and easily includes over a dozen different organisms, many of them potential pathogens. The quantitative nature of the vaginal flora also is a factor in development of symptoms. This complex milieu is further varied by nature's changes over the years from birth to menopause. Artificial changes occurring as the result of contraceptive measures may also disrupt the resident vaginal flora. Each patient may be her own control, and the balance that leads to an asymptomatic state may vary from individual to individual. An understanding of the normal situation may be the best guide to diagnosing abnormal conditions and directing appropriate therapy.