Normal flora of the vagina and cervix include non-sporing anaerobes (not Bacteroides fragilis group), lactobacilli, Staphylo coccus epidermidis, diphtheroids and less commonly coliforms, Enterococcus spp., Candida spp., group B beta-haemolytic streptococci and Staphylo coccus aureus. The composition of this flora changes before and after puberty and the menopause, and during the menstrual cycle. Use of antibiotics favours an increase in coliforms and Candida spp., and a decrease in lactobacilli.
Risk factors: Pregnancy, diabetes mellitus, oral contraceptive pill, antibiotics, immunosuppression (e.g. therapeutic or HIV-related (>160)).
Clinical features: Pruritis, ‘external’ dysuria and dyspareunia, vaginal discharge. On examination, vulval erythema and excoriation and vaginal discharge.
Organisms: Candida albicans (>367), less often other Candida spp.
Microbiological investigations: Gram stain and culture of high vaginal swab. As Candida albicans is a frequent commensal (20% of asymptomatic women), diagnosis depends on the association of positive culture result with appropriate history and clinical findings.
Differential diagnosis: Trichomoniasis (>92), bacterial vaginosis.
Antibiotic management: Clotrimazole, econazole and miconazole are all available in a variety of topical preparations, including single-dose pessaries. Nystatin is an alternative. In severe cases or in the immunocompromised, oral fluconazole may be required.
Comments: Chronic recurrent candidiasis is probably due to failure of eradication of infection during treatment of acute attacks. Recurrences should be treated for longer than usual or with a course of oral fluconazole, which will abolish gut colonization, which may act as a reservoir. Reinfection from a partner is possible — 20% of male partners have penile colonization, and topical therapy is recommended. Prolonged suppressive therapy with fluconazole (100 mg weekly) may rarely be necessary. Some refractory cases are due to antifungal resistance, so identification and susceptibility testing may be useful 2.
It has also been suggested that some women with recurrent candidiasis have immune hyper-sensitivity to low numbers of Candida.
Some topical vaginal preparations may damage condoms and diaphragms. Up-to-date information is available in datasheets or the BNF.
Gardnerella vaginalis (>302) is a vaginal commensal organism. Under certain circumstances, it acts in synergy with other commensal anaerobes to multiply and inhibit the growth of lactobacilli and other vaginal flora.
Clinical features: Many patients are asymptomatic. Mild vaginal discharge with a fishy odour and pruritis may occur. On examination, there is little or no vaginal inflammation. Discharge is thin, grey and homogenous. When potassium hydroxide is added, a fishy odour is liberated (‘whiff test’).
Organisms: Gardnerella vaginalis is a vaginal commensal organism, so isolation by culture is not significant. Quantification and culture for anaerobes is not routinely practicable.
Microbiological investigations: Microscopy of wet preparation characteristically shows ‘clue cells’ — squamous epithelial cells studded with Gardnerella. Diagnosis depends on the presence of three out of four of the following: positive whiff test, clue cells, characteristic vaginal discharge and vaginal pH > 5.0.
Differential diagnosis: Candidiasis (>82), trichomoniasis (>92), gonorrhoea (>86), non-specific cervicitis (>87).
Antibiotic management: Metronidazole (400 mg q8h for one week) or topical clindamycin (2% cream, 5 g q24h for 1 week). Metronidazole is relatively contraindicated during pregnancy. Ampicillin is effective in some cases and has been used during pregnancy. Asymptomatic cases should not be treated; yeast superinfection reported in up to 20% after oral metronidazole.
Complications: Bacterial vaginosis is associated with increased risk of premature labour, chorioamnionitis, and puerperal sepsis, but the value of screening and treating asymptomatic pregnant women remains to be established.
Endometrial infection following delivery; causes -30% of puerperal fevers.
Risk factors: Caesarian section is associated with a greatly increased risk (20-55% incidence without prophylaxis vs. 2-5% for vaginal delivery). Other factors include prolonged labour, retained products of conception and prolonged rupture of membranes.
Clinical features: Fever, uterine tenderness, foul lochia, leucocytosis. Malaise, abdominal pain and rigors.
Organisms: Mixed aerobic and anaerobic genital flora including coliforms, Streptococcus ‘milleri’ Enterococcus spp., group B beta-haemolytic streptococci, anaerobic streptococci, Bacteroides spp., Gardnerella vaginalis, genital Mycoplasma spp., Clostridium spp.
Microbiological investigations: Culture of lochia and blood.
Differential diagnosis: Pyelonephritis or urinary tract infection (40% of puerperal fevers), wound infection (~7% of puerperal fevers).
Antibiotic management: Parenteral cephalosporin + metronidazole or clindamycin + gentamicin.
Complications: Pelvic abscess formation. Sepsis syndrome (>185). Septic pelvic thrombophlebitis is an uncommon but important complication. It is due to mixed aerobic and anaerobic flora, but in particular, Bacteroides spp. It presents in two ways. Ovarian vein thrombosis presents with acute onset of severe abdominal pain and signs of peritonism. 50% of cases have a palpable abdominal mass. In other patients onset is gradual, with spiking fevers that are unresponsive to antibiotics. Septic pulmonary embolism (>35) mayfollow. Venography and CT scanning are required. Treatment consists of antibiotic therapy as above, with heparinization and consideration of surgical intervention.
Infection is associated with illegal and occasionally therapeutic abortion. The history of illegal or attempted abortion may not be obtained, and the diagnosis should be considered in any febrile woman with vaginal bleeding during the first half of pregnancy.
Risk factors: Incomplete removal of the products of conception. Uterine perforation. Pre-existing untreated infection with Neisseria gonorrhoeae or Chlamydia trachomatis.
Clinical features: Fever, rigors, abdominal pain, pelvic tenderness, history of passage of products of conception. Uterine perforation may follow with evidence of pelvic abscess or peritonitis. On examination, there may be a tender, enlarged uterus, foul cervical discharge and open os with evidence of passage of products of conception or instrumentation.
Organisms: As for puerperal infection, plus Neisseria gonorrhoeae and Chlamydia trachomatis. Clostridial infection (‘uterine gas gangrene’) may sometimes cause full-blown clostridial septicaemia with haemolysis, jaundice, shock, renal failure and disseminated intravascular coagulation (>115,314).
Microbiological investigations: Gram stain and culture of discharge. Blood cultures.
Other investigations: Imaging, usually ultrasound, to define pelvic abscess.
Antibiotic management: As forpuerperal sepsis, plus doxycycline if chlamydia involved.
Supportive management: Removal of remaining products of conception and exclusion of uterine perforation.
Complications: See puerperal sepsis (>83).
Amniotic fluid infection usually follows rupture of the membranes, although it may occur as a complication of instrumentation, e.g. amniocentesis.
Clinical features: Fever, maternal and foetal tachycardia, uterine tenderness, malodorous amniotic fluid.
Organisms: As forpuerperal infection.
Microbiological investigations: Culture of amniotic fluid and blood.
Antibiotic management: Parenteral cephalosporin + metronidazole.
Supportive management: Prompt delivery is required. Antibiotics should be given intrapartum rather than waiting until post-delivery.
Prophylactic ampicillin and erythromycin are recommended by some experts for mothers with preterm premature rupture of membranes without evidence of intra-amniotic infection, to prolong pregnancy.
Certain vaginal infections are suspected of causing premature rupture of membranes (e.g. bacterial vaginosis >82, heavy colonization with group beta-haemolytic streptococci >140); appropriate treatment may prevent this complication.
Infection of Bartholin’s glands may present as a localized abscess or as cellulitis of the surrounding skin. Infection is usually due to mixed genital flora (>82); Neisseria gonorrhoeae is a rarer cause which must be excluded by Gram stain and culture (including en docervical, rectal and throat swabs). For localized abscess, surgical incision and drainage is required. For cellulitis, co-amoxiclav or amoxicillin + metronidazole may be given. For severe infection, give parenteral cephalosporin + metronidazole or clindamycin + gentamicin.
Toxic shock syndrome (TSS)
Risk factors: Most cases are associated with tampon use in menstruating women, but it can complicate any focal staphylococcal infection. Menstrual cases have been reported in women who have not used tampons; non-menstrual cases have occurred secondary to surgical wound infection, nasal packing, postpartum, due to infection of intrauterine contraceptive devices and in association with post-influenzal staphylococcal pneumonia (>28). The incidence of menstrual cases has fallen dramatically since the withdrawal of high absorbency tampons.
Pathogenesis: A number of staphylococcal superantigen toxins have been associated with TSS, including toxic shock syndrome toxin (TSST-1, >90% of menstrual cases, =50% of non-menstrual cases), enterotoxin B (=40% of non-menstrual, TSST-1 negative cases), less frequently enterotoxins A-D (>249).
Clinical features: Median onset in menstrual cases is 2 days after onset of menses. Diagnosis is clinical, since Staphylococcus aureus may not always be isolated. Diagnostic criteria have been established to allow recognition and surveillance. Patients should have all of the following: fever (>38.9°C); diffuse macular rash, which should desquamate 1-2 weeks after the onset of illness; hypotension (SBP <90mmHg); plus at least three of the following categories of multi-organ involvement: (1) vomiting or diarrhoea; (2) severe myalgia with elevated creatine phosphokinase (>2 x normal); (3) mucous hyperaemia affecting vagina, oropharynx or conjunctiva; (4) renal failure (creatinine >2 x normal) or pyuria in the absence of urinary tract infection; (5) abnormal liver function tests; (6) thrombocytopenia (<100 x 109/L); (7) disorientation or altered conscious level without focal neurological signs. These criteria were established for epidemiological surveillance and should not be used to preclude treatment if the suspicion of TSS ishigh.
Organisms: Staphylo coccus aureus. A similar illness may rarely be caused by exotoxin producing β-haemolytic streptococci.
Microbiological investigations: Culture of blood, vagina, nares, urine and, if there is doubt about the diagnosis, CSF may be required, in particular to exclude other infections such as meningococcaemia (>185). Isolated organisms can be tested for toxin production in vitro; convalescent serology is also useful 2.
Differential diagnosis: Meningococcaemia (>185), scarlet fever (>135), Gram-negative b acteraemia (> 185).
Antibiotic management: Antibiotics prevent relapse, but have not been shown to modify the course of the illness, which is toxin-mediated. However, in vitro studies suggest that antibiotics that inhibit protein synthesis may reduce toxin production and therefore we recommend clindamycin plus flucloxacillin. Flucloxacillin (1 g 6hly) should be given iv for a week, then orally for another week to ensure eradication. If meningococcaemia cannot be excluded, then give parenteral cephalosporin initially instead of the flucloxacillin. IV immunoglobulin has been advocated, but has not been demonstrated to be effective. High-dose steroids (methylprednisolone 10-30 mg/kg/ day) have also been advocated. Retrospective studies suggest benefit, but there has been no definitive controlled trial.
Supportive management: Supportive management is most important. Fluid replacement and monitoring, pressor agents and other intensive care therapies may be required (> 187).