Hemsell 1994

Methods	Randomized controlled trial.
Participants	Inclusion criteria: clinical diagnosis of acute PID hospitalized at 1 of 6 sites for treatment. Acute PID diagnosed in women with lower abdominal and pelvic pain and lower abdominal and cervical motion and adnexal tenderness in addition to ≥ 1 of the following: oral temperature ≥ 38.0 °C; leukocyte count ≥ 10,500/mm3; elevated ESR; endocervical specimen positive for Gram‐negative intracellular diplococci; endocervical or endometrial culture positive for N gonorrhoeae or C trachomatis; ultrasound findings consistent with an adnexal inflammatory mass; or purulence in or a positive culture of intraperitoneal material obtained at either culdocentesis or optional laparoscopy. Exclusion criteria: ruptured tubo‐ovarian or pelvic abscess; history of hypersensitivity to penicillin, cephalosporins, clindamycin, aminoglycosides, or tetracycline; among women with IUD in place, those who permitted the removal of the device within 48 h were included and those who did not were excluded; pregnancy or lactation; renal impairment (a serum creatinine level about 2 mg/dL), neutropenia (< 1000 neutrophils/mm3), receipt of another investigational drug or another antibiotic up to 2 weeks before the time of anticipated enrolment; and known or suspected active bacterial infection other than acute PID that might subsequently require concomitant therapy. Number of women randomized: 344. Number of women analyzed: group A: 109; group B: 110; group C: 108. Number of withdrawal/exclusions/loss to follow‐up and reasons: 52 women (15%) were not evaluable, 21 enrolled incorrectly (i.e. despite a violation of inclusion or exclusion criteria, or both), aII given an incorrect first dose of study drug or were subsequently given incorrect doses, 10 left hospital against medical advice, 5 treated for < 48 h, 2 withdrew, 2 had adverse reactions resulting in the cessation of treatment, and 1 given penicillin for the treatment of syphilis. Of the 2 women with adverse reactions, 1 developed blisters on her lips after the third dose of cefotetan + doxycycline, and the other developed hives after the initial dose of cefoxitin. All 5 women who were not evaluable because they received < 48 h of therapy had ≥ 1 abscesses, and 3/5 women underwent surgery because of worsening symptoms. 2/5 women were in group A, 2 were in group B, and 1 was in group 3. 20 of the unevaluable women were in group A, 20 were in group B, and 12 were in group C. Number of centres: 6. Age (mean ± SD) (years): success group: 24.7 ± 4.9; failure group: 26.2 ± 5.7. Country: US.
Interventions	Group A: cefoxitin 2 g IV every 6 h + doxycycline 100 mg every 12 h; followed by doxycycline 100 mg PO twice daily for a total of 10‐14 days. Group B: clindamycin 900 mg IV + gentamicin 1.5 mg/kg every 8 h after an initial gentamicin loading dose calculated at 2 mg/kg followed by clindamycin 450 mg PO 4 times daily for a total of 10‐14 days. Group C: cefotetan 2 g IV + doxycycline 100 mg every 12 h, followed by doxycycline 100 mg PO twice daily for a total of 10‐14 days.
Outcomes	Primary outcome: clinical cure defined as reduction of the severity score by ≥ 70%, with a normal temperature and leukocyte count. Secondary outcome: none reported.
Notes	Ethical approval: consent forms were approved by the local institutional review board at each centre. Informed consent: women aged 16‐18 years old had to have parental consent, and women aged ≥19 years had to give their own consent. Source of funding: ICI Pharmaceuticals Group (now ZENECA, Inc.), Wilmington, Delaware. No conflicts of interest reported.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Not described how randomization codes were generated.
Allocation concealment (selection bias)	Unclear risk	Not stated.
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open‐label study.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open‐label study.
Incomplete outcome data (attrition bias) All outcomes	Low risk	292/343 women were analyzed (15% were not evaluable).
Selective reporting (reporting bias)	Unclear risk	No trial protocol found.
Other bias	Unclear risk	Not stated.