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Meta-Analysis
. 2020 Aug 20;8(8):CD010285.
doi: 10.1002/14651858.CD010285.pub3.

Antibiotic therapy for pelvic inflammatory disease

Affiliations
Meta-Analysis

Antibiotic therapy for pelvic inflammatory disease

Ricardo F Savaris et al. Cochrane Database Syst Rev. .

Abstract

Background: Pelvic inflammatory disease (PID) affects 4% to 12% of women of reproductive age. The main intervention for acute PID is broad-spectrum antibiotics administered intravenously, intramuscularly or orally. We assessed the optimal treatment regimen for PID. OBJECTIVES: To assess the effectiveness and safety of antibiotic regimens to treat PID.

Search methods: In January 2020, we searched the Cochrane Sexually Transmitted Infections Review Group's Specialized Register, which included randomized controlled trials (RCTs) from 1944 to 2020, located through hand and electronic searching; CENTRAL; MEDLINE; Embase; four other databases; and abstracts in selected publications.

Selection criteria: We included RCTs comparing antibiotics with placebo or other antibiotics for the treatment of PID in women of reproductive age, either as inpatient or outpatient treatment. We limited our review to a comparison of drugs in current use that are recommended by the 2015 US Centers for Disease Control and Prevention guidelines for treatment of PID.

Data collection and analysis: We used standard methodological procedures expected by Cochrane. Two authors independently extracted data, assessed risk of bias and conducted GRADE assessments of the quality of evidence.

Main results: We included 39 RCTs (6894 women) in this review, adding two new RCTs at this update. The quality of the evidence ranged from very low to high, the main limitations being serious risk of bias (due to poor reporting of study methods and lack of blinding), serious inconsistency, and serious imprecision. None of the studies reported quinolones and cephalosporins, or the outcomes laparoscopic evidence of resolution of PID based on physician opinion or fertility outcomes. Length of stay results were insufficiently reported for analysis. Regimens containing azithromycin versus regimens containing doxycycline We are uncertain whether there was a clinically relevant difference between azithromycin and doxycycline in rates of cure for mild-moderate PID (RR 1.18, 95% CI 0.89 to 1.55; 2 RCTs, 243 women; I2 = 72%; very low-quality evidence). The analyses may result in little or no difference between azithromycin and doxycycline in rates of severe PID (RR 1.00, 95% CI 0.96 to 1.05; 1 RCT, 309 women; low-quality evidence), or adverse effects leading to discontinuation of treatment (RR 0.71, 95% CI 0.38 to 1.34; 3 RCTs, 552 women; I2 = 0%; low-quality evidence). In a sensitivity analysis limited to a single study at low risk of bias, azithromycin probably improves the rates of cure in mild-moderate PID (RR 1.35, 95% CI 1.10 to 1.67; 133 women; moderate-quality evidence), compared to doxycycline. Regimens containing quinolone versus regimens containing cephalosporin The analysis shows there may be little or no clinically relevant difference between quinolones and cephalosporins in rates of cure for mild-moderate PID (RR 1.05, 95% CI 0.98 to 1.14; 4 RCTs, 772 women; I2 = 15%; low-quality evidence), or severe PID (RR 1.06, 95% CI 0.91 to 1.23; 2 RCTs, 313 women; I2 = 7%; low-quality evidence). We are uncertain whether there was a difference between quinolones and cephalosporins in adverse effects leading to discontinuation of treatment (RR 2.24, 95% CI 0.52 to 9.72; 6 RCTs, 1085 women; I2 = 0%; very low-quality evidence). Regimens with nitroimidazole versus regimens without nitroimidazole There was probably little or no difference between regimens with or without nitroimidazoles (metronidazole) in rates of cure for mild-moderate PID (RR 1.02, 95% CI 0.95 to 1.09; 6 RCTs, 2660 women; I2 = 50%; moderate-quality evidence), or severe PID (RR 0.96, 95% CI 0.92 to 1.01; 11 RCTs, 1383 women; I2 = 0%; moderate-quality evidence). The evidence suggests that there was little to no difference in in adverse effects leading to discontinuation of treatment (RR 1.05, 95% CI 0.69 to 1.61; 17 studies, 4021 women; I2 = 0%; low-quality evidence). . In a sensitivity analysis limited to studies at low risk of bias, there was little or no difference for rates of cure in mild-moderate PID (RR 1.05, 95% CI 1.00 to 1.12; 3 RCTs, 1434 women; I2 = 0%; high-quality evidence). Regimens containing clindamycin plus aminoglycoside versus quinolone We are uncertain whether quinolone have little to no effect in rates of cure for mild-moderate PID compared to clindamycin plus aminoglycoside (RR 0.88, 95% CI 0.69 to 1.13; 1 RCT, 25 women; very low-quality evidence). The analysis may result in little or no difference between quinolone vs. clindamycin plus aminoglycoside in severe PID (RR 1.02, 95% CI 0.87 to 1.19; 2 studies, 151 women; I2 = 0%; low-quality evidence). We are uncertain whether quinolone reduces adverse effects leading to discontinuation of treatment (RR 0.21, 95% CI 0.02 to 1.72; 3 RCTs, 163 women; I2 = 0%; very low-quality evidence). Regimens containing clindamycin plus aminoglycoside versus regimens containing cephalosporin We are uncertain whether clindamycin plus aminoglycoside improves the rates of cure for mild-moderate PID compared to cephalosporin (RR 1.02, 95% CI 0.95 to 1.09; 2 RCTs, 150 women; I2 = 0%; low-quality evidence). There was probably little or no difference in rates of cure in severe PID with clindamycin plus aminoglycoside compared to cephalosporin (RR 1.00, 95% CI 0.95 to 1.06; 10 RCTs, 959 women; I2= 21%; moderate-quality evidence). We are uncertain whether clindamycin plus aminoglycoside reduces adverse effects leading to discontinuation of treatment compared to cephalosporin (RR 0.78, 95% CI 0.18 to 3.42; 10 RCTs, 1172 women; I2 = 0%; very low-quality evidence).

Authors' conclusions: We are uncertain whether one treatment was safer or more effective than any other for the cure of mild-moderate or severe PID Based on a single study at a low risk of bias, a macrolide (azithromycin) probably improves the rates of cure of mild-moderate PID, compared to tetracycline (doxycycline).

Trial registration: ClinicalTrials.gov NCT01799356.

PubMed Disclaimer

Conflict of interest statement

RFS, DGF, JM and RVD certify that they do not have any affiliations with, or involvement in, any organization or entity with a direct financial interest in the subject matter of this review (e.g. employment, consultancy, stock ownership, honoraria, expert testimony). JR has received consultancy payments from Mycovia and GlaxoSmithKline and conference support from Janssen and American Society for Microbiology, has research grants pending from Gilead, Viiv and Pfizer, and owns stock options in AstraZeneca and GlaxoSmithKline.

They disclose that two of the authors (RFS and JR) had two publications used in the analysis. RFS and JR did not participate in the process for considering these studies for inclusion, data extraction, and grading for risk of bias.

Figures

1
1
Study flow diagram. PID: pelvic inflammatory disease; RCT: randomised controlled trial.
2
2
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
3
3
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
4
4
Forest plot of comparison: 1 Regimens containing macrolides (azithromycin) versus tetracycline (doxycycline), outcome: 1.1 Effectiveness of cure in mild‐moderate PID.
5
5
Forest plot of comparison: 1 Regimens containing macrolides (azithromycin) versus tetracycline (doxycycline), outcome: 1.2 Sensitivity analysis by risk of bias: effectiveness of cure in mild‐moderate PID.
6
6
Forest plot of comparison: 1 Regimens containing macrolides (azithromycin) versus tetracycline (doxycycline), outcome: 1.3 Effectiveness of cure in severe PID.
7
7
Forest plot of comparison: 2 Regimens containing quinolones versus cephalosporins, outcome: 2.1 Effectiveness of cure in mild‐moderate PID.
8
8
Forest plot of comparison: 2 Regimens containing quinolones versus cephalosporins, outcome: 2.2 Effectiveness of cure in severe PID.
9
9
Forest plot of comparison: 2 Regimens containing quinolones versus cephalosporins, outcome: 2.3 Any antibiotic‐related adverse effect leading to discontinuation.
10
10
Forest plot of comparison: 3 Regimens containing nitroimidazoles versus no nitroimidazoles, outcome: 3.1 Effectiveness of cure in mild‐moderate PID.
11
11
Forest plot of comparison: 3 Regimens containing nitroimidazoles versus no nitroimidazoles, outcome: 3.3 Effectiveness of cure in severe PID.
12
12
Funnel plot of comparison: 3.3 Effectiveness of cure in severe pelvic inflammatory disease in regimens containing nitroimidazoles versus without nitroimidazoles.
13
13
Forest plot of comparison: 4 Regimens containing clindamycin plus aminoglycoside versus quinolone, outcome: 4.1 Effectiveness of cure in mild‐moderate pelvic inflammatory disease.
14
14
Forest plot of comparison: 4 Regimens containing clindamycin plus aminoglycoside versus quinolone, outcome: 4.2 Effectiveness of cure in severe pelvic inflammatory disease.
15
15
Forest plot of comparison: 5 Regimens containing clindamycin plus aminoglycoside versus cephalosporin, outcome: 5.1 Effectiveness of cure in mild‐moderate pelvic inflammatory disease.
16
16
5.2 Effectiveness of cure in severe pelvic inflammatory disease in regimens containing clindamycin plus aminoglycoside versus cephalosporin.
1.1
1.1. Analysis
Comparison 1: Regimens containing macrolides (azithromycin) versus tetracycline (doxycycline), Outcome 1: Effectiveness of cure in mild‐moderate PID
1.2
1.2. Analysis
Comparison 1: Regimens containing macrolides (azithromycin) versus tetracycline (doxycycline), Outcome 2: Sensitivity analysis by risk of bias: effectiveness of cure in mild‐moderate PID
1.3
1.3. Analysis
Comparison 1: Regimens containing macrolides (azithromycin) versus tetracycline (doxycycline), Outcome 3: Effectiveness of cure in severe PID
1.4
1.4. Analysis
Comparison 1: Regimens containing macrolides (azithromycin) versus tetracycline (doxycycline), Outcome 4: Any antibiotic‐related adverse effect leading to discontinuation use of macrolide versus tetracycline
2.1
2.1. Analysis
Comparison 2: Regimens containing quinolones versus cephalosporins, Outcome 1: Effectiveness of cure in mild‐moderate PID
2.2
2.2. Analysis
Comparison 2: Regimens containing quinolones versus cephalosporins, Outcome 2: Effectiveness of cure in severe PID
2.3
2.3. Analysis
Comparison 2: Regimens containing quinolones versus cephalosporins, Outcome 3: Any antibiotic‐related adverse effect leading to discontinuation
3.1
3.1. Analysis
Comparison 3: Regimens containing nitroimidazoles versus no nitroimidazoles, Outcome 1: Effectiveness of cure in mild‐moderate PID
3.2
3.2. Analysis
Comparison 3: Regimens containing nitroimidazoles versus no nitroimidazoles, Outcome 2: Sensitivity analysis by risk of bias: effectiveness of cure in mild‐moderate PID
3.3
3.3. Analysis
Comparison 3: Regimens containing nitroimidazoles versus no nitroimidazoles, Outcome 3: Effectiveness of cure in severe PID
3.4
3.4. Analysis
Comparison 3: Regimens containing nitroimidazoles versus no nitroimidazoles, Outcome 4: Any antibiotic‐related adverse effect leading to discontinuation
4.1
4.1. Analysis
Comparison 4: Regimens containing clindamycin plus aminoglycoside versus quinolone, Outcome 1: Effectiveness of cure in mild‐moderate PID
4.2
4.2. Analysis
Comparison 4: Regimens containing clindamycin plus aminoglycoside versus quinolone, Outcome 2: Effectiveness of cure in severe PID
4.3
4.3. Analysis
Comparison 4: Regimens containing clindamycin plus aminoglycoside versus quinolone, Outcome 3: Any antibiotic‐related adverse effect leading to discontinuation
5.1
5.1. Analysis
Comparison 5: Regimens containing clindamycin plus aminoglycoside versus cephalosporin, Outcome 1: Effectiveness of cure in mild‐moderate PID
5.2
5.2. Analysis
Comparison 5: Regimens containing clindamycin plus aminoglycoside versus cephalosporin, Outcome 2: Effectiveness of cure in severe PID
5.3
5.3. Analysis
Comparison 5: Regimens containing clindamycin plus aminoglycoside versus cephalosporin, Outcome 3: Any antibiotic‐related adverse effect leading to discontinuation

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References

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    1. Bruhat MA, Le Bouedec G, Pouly JL, Mage G, Canis M. Treatment of acute salpingitis with sulbactam/ampicillin. International Journal of Gynecology & Obstetrics 1989;31 Suppl(2):41-6. - PubMed
Bruno 1985 {published data only}
    1. Bruno V, Lombardo M, Schimberni M, Torregrossa G, Pepe C, Carenza L. A clinical trial with the new antibiotic combination piperacillin/flucloxacillin used on gynaecological postoperative infections. Current Therapeutic Research 1985;38(3):465-73.
Cao 2017 {published data only}
    1. Cao C, Luo A, Wu P, Weng D, Zheng H, Wang S. Efficacy and safety of morinidazole in pelvic inflammatory disease: results of a multicenter, double-blind, randomized trial. European Journal of Clinical Microbiology & Infectious Diseases 2017;36:1225-30. [DOI: 10.1007/s10096-017-2913-z] [PMID: ] - DOI - PubMed
Carty 1973 {published data only}
    1. Carty MJ. The use of oxyphenbutazone ('Tanderil') in acute pelvic inflammatory disease. Current Medical Research and Opinion 1973;1(4):203-4. - PubMed
Chatwani 1997 {published data only}
    1. Chatwani A, Dandalou V, Harmanli O, Nyirjesy P. Trospectomycin in acute pelvic inflammatory disease: a preliminary report. Infectious Diseases in Obstetrics and Gynecology 1997;5(3):215-8. - PMC - PubMed
Confino 1988 {published data only}
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De Beer 1983 {published data only}
    1. De Beer JA, Van den Ende J, Odendaal HJ. Efficacy of ampicillin and cefoxitin in the treatment of acute pelvic inflammatory disease. A comparative study. South African Medical Journal 1983;64:733-5. - PubMed
Drasa 2010 {published data only}
    1. Drasa K, Koci E. Azithromycin vs. clarithromycin and both combination in treatment of mycoplasma genitalium. European Urology Supplements 2010;9(2):172.
Drusano 1982 {published data only}
    1. Drusano GL, Warren JW, Saah AJ, Caplan ES, Tenney JH, Hansen S, et al. A prospective randomized controlled trial of cefoxitin versus clindamycin-aminoglycoside in mixed anaerobic-aerobic infections. Surgery, Gynecology & Obstetrics 1982;154(5):715-20. - PubMed
Duarte 1995 {published data only}
    1. Duarte G, Quintana SM, Gir E, Marana HR, Cunha SP. Evaluation of doxycycline for the complementary treatment of acute inflammatory pelvic disease. A double-blind study [Avaliação da doxiciclina como tratamento complementar da doença inflamatória pélvica aguda – Estudo duplo-cego]. Revista Brasileira de Medicina do Esporte 1995;52(6):651-6.
Faro 1988 {published data only}
    1. Faro S, Martens MG, Phillips LE, Lapread E, Riddle GD, Turner RM. Ceftizoxime versus cefotaxime in the treatment of hospitalized patients with pelvic inflammatory disease. Current Therapeutic Research 1988;43(3):349-54.
Fedele 1989 {published data only}
    1. Fedele L, Acaia B, Marchini M, Grassi R, Benzi-Cipelli R, Bonino S. Treatment of Chlamydia trachomatis endometritis with josamycin. Journal of Chemotherapy 1989;1(4 Suppl):911-2. - PubMed
Feng 2019 {published data only}
    1. Feng XL, Jiang S, Chen J, Liu X, Zhang Y, Chen L. Effect of Fuyanshu capsules combined with antibiotics on inflammatory factors in patients with pelvic inflammatory disease. Zhongguo Zhong Yao za Zhi [China Journal of Chinese Materia Medica] 2019;44(12):2637-43. - PubMed
Frongillo 1992 {published data only}
    1. Frongillo RF, Custo GM, Gilardi G, Martella L, Palumbo M. Imipenem versus netilmicin plus chloramphenicol in gynecological upper tract infections: a comparative study. Chemotherapy 1992;5(1):41-4.
Gall 1981 {published data only}
    1. Gall SA, Kohan AP, Ayers OM, Hughes CE, Addison WA, Hill GB. Intravenous metronidazole or clindamycin with tobramycin for therapy of pelvic infections. Obstetrics & Gynecology 1981;57(1):51-8. - PubMed
Gall 1990a {published data only}
    1. Gall S. Therapeutic dilemmas in the treatment of pelvic infections. Journal of Reproductive Medicine 1990;35(11 Suppl):1091-4. - PubMed
Gall 1990b {published data only}
    1. Gall SA, Constantine L. Comparative evaluation of clindamycin versus clindamycin plus tobramycin in the treatment of acute pelvic inflammatory disease. Obstetrics & Gynecology 1990;75(2):282-6. - PubMed
Gerber 1992 {published data only}
    1. Gerber B, Wilken H, Zacharias K, Barten G, Splitt G. Treatment of acute salpingitis with tetracycline/metronidazole with or without additional balneotherapy. Augmentan or ciprofloxacin/metronidazole: a second-look-laparoscopy study [Zur Behandlung der akuten Salpingitis mit Tetracyclin/Metronidazol mit oder ohne zusätzliche Heilbadkur, Augmentan oder Ciprofloxacin/Metronidazol: Eine second look-Laparoskopie-Studie]. Geburtshilfe und Frauenheilkunde 1992;52:165-70. - PubMed
Gerstner 1990 {published data only}
    1. Gerstner GJ. Comparison of ceftriaxone (1 x 1 g/day) versus cefotaxime (3 x 1 g/day) for gynecologic and obstetric infections. A randomized clinical trial. Gynecologic and Obstetric Investigation 1990;29(4):273-7. - PubMed
Ghomian 2012 {published data only}
    1. Ghomian N, HafiziI L, Tavassoli F, Ahrari RT. Comparing ceftriaxone plus azithromycin or doxycycline for outpatient treatment in pelvic inflammatory disease [مقايسه سفترياكسون و آزيترومايسين با سفترياكسون و داكسي سيكلين در درمان سرپايي بيماري التهابي لگن]. Iranian Journal of Obstetrics, Gynecology and Infertility 2012;14(8):1-8.
Giamarellou 1982 {published data only}
    1. Giamarellou H, Volanaki M, Avlami A, Tsatsiadis K, Petrochilos E, Daikos GK. Ornidazole versus clindamycin: comparative evaluation in the treatment of 140 serious anaerobic infections. Chemotherapy 1982;28(6):502-11. - PubMed
Gibbs 1980 {published data only}
    1. Gibbs RS. A trial of spectinomycin hydrochloride compared with aqueous penicillin G plus kanamycin for treatment of severe pelvic inflammatory disease. Sexually Transmitted Diseases 1980;7(1):21-3. - PubMed
Gjonnaess 1981 {published data only}
    1. Gjonnaess H, Dalaker K, Urnes A, Norling B, Kville G, Mardh P, et al. Treatment of pelvic inflammatory disease. Effects of lymecycline and clindamycin. Current Therapeutic Research 1981;29(6):885-92.
Grafford 1980 {published data only}
    1. Grafford K, Guttorm E, Kristensen GB, Philipson T, Selnes A. Bacampicillin in the treatment of pelvic inflammatory disease: a study of two dosage regimens. Infection 1980;8(6):290-2.
Grafford 1981 {published data only}
    1. Grafford K, Nilsson BS. Twice daily dosage of bacampicillin: a summary of clinical documentation. Journal of Antimicrobial Chemotherapy 1981;8(Suppl C):119-27. - PubMed
Gunning 1986a {published data only}
    1. Gunning JE. A comparison of piperacillin and clindamycin plus gentamicin in women with pelvic infections. Surgery, Gynecology & Obstetrics 1986;163:156-62. - PubMed
Gunning 1986b {published data only}
    1. Gunning J. A comparison of parenteral sulbactam/ampicillin versus clindamycin/gentamicin in the treatment of pelvic inflammatory disease. Drugs 1986;31(Suppl 2):14-7. - PubMed
Hager 1989 {published data only}
    1. Hager WD, Pascuzzi M, Vernon M. Efficacy of oral antibiotics following parenteral antibiotics for serious infections in obstetrics and gynecology. Obstetrics & Gynecology 1989;73(3 Pt 1):326-29. - PubMed
Harding 1982 {published data only}
    1. Harding G, Vincelette J, Rachlis A, Fong I, Mandell L, Feld R, et al. A preliminary report on the use of ceftizoxime versus clindamycin/tobramycin for the therapy of intra-abdominal and pelvic infections. Journal of Antimicrobial Chemotherapy 1982;10(Suppl C):191-2. - PubMed
Harding 1984 {published data only}
    1. Harding GK, Nicolle LE, Haase DA, Aoki FY, Stiver HG, Blanchard RJ, et al. Prospective, randomized, comparative trials in the therapy for intraabdominal and female genital tract infections. Reviews of Infectious Diseases 1984;6(Suppl 1):S283-92. - PubMed
Hemsell 1982 {published data only}
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Hemsell 1987 {published data only}
    1. Hemsell DL, Hemsell PG, Heard MC, Nobles BJ. Piperacillin and a combination of clindamycin and gentamicin for the treatment of hospital and community acquired acute pelvic infections including pelvic abscess. Surgery, Gynecology & Obstetrics 1987;165(3):223-9. - PubMed
Hemsell 1988a {published data only}
    1. Hemsell DL, Heard MC, Hemsell PG, Nobles BJ. Sulbactam/ampicillin versus cefoxitin for uncomplicated and complicated acute pelvic inflammatory disease. Drugs 1988;35(Suppl 7):39-42. - PubMed
Hemsell 1988b {published data only}
    1. Hemsell DL, Wendel GD, Gall SA, Newton ER, Gibbs RS, Knuppel RA, et al. Multicenter comparison of cefotetan and cefoxitin in the treatment of acute obstetric and gynecologic infections. American Journal of Obstetrics & Gynecology 1988;158(3 pt 2):722-77. - PubMed
Hemsell 1988c {published data only}
    1. Hemsell DL, Nobles BJ, Heard MC, Hemsell PG. Upper and lower reproductive tract bacteria in 126 women with acute pelvic inflammatory disease. Microbial susceptibility and clinical response to four therapeutic regimens. Journal of Reproductive Medicine 1988;33(10):799-805. - PubMed
Hemsell 1988d {published data only}
    1. Hemsell DL, Heard MC, Hemsell PG, Nobles BJ. Sulbactam/ampicillin versus cefoxitin for uncomplicated and complicated acute pelvic inflammatory disease. Drugs 1988;35(Suppl 7):39-42. - PubMed
Hemsell 1990 {published data only}
    1. Hemsell DL, Bawdon RE, Hemsell PG, Nobles BJ, Heard MC. Single-agent therapy for acute pelvic inflammatory disease: sulbactam/ampicillin versus cefoxitin. Journal of International Medical Research 1990;18(Suppl 4):85D-9D. - PubMed
Hemsell 1991 {published data only}
    1. Hemsell DL, Heard MC, Nobles BJ. Comparative bacteriology of parenteral single-agent vs. combination therapy in salpingitis. Advances in Therapy 1991;8(1):27-35.
Hemsell 1993 {published data only}
    1. Hemsell DL, Wendel GD, Hemsell PG, Heard ML, Nobles BJ. Inpatient treatment for uncomplicated and complicated acute pelvic inflammatory disease: ampicillin/sulbactam vs. cefoxitin. Infectious Diseases in Obstetrics and Gynecology 1993;1(3):123-9. - PMC - PubMed
Hemsell 1997 {published data only}
    1. Hemsell DL, Martens MG, Faro S, Gall S, McGregor JA. A multicenter study comparing intravenous meropenem with clindamycin plus gentamicin for the treatment of acute gynecologic and obstetric pelvic infections in hospitalized women. Clinical Infectious Diseases 1997;24(Suppl 2):S222-30. - PubMed
Henry 1985 {published data only}
    1. Henry SA. Overall clinical experience with aztreonam in the treatment of obstetric-gynecologic infections. Reviews of Infectious Diseases 1985;7(Suppl 4):S703-8. - PubMed
Holloway 1988 {published data only}
    1. Holloway WJ. Infection in women. Clinical experience with beta-lactamase inhibitors. Journal of Reproductive Medicine 1988;33(6 Suppl):595-7. - PubMed
Ibrahim 1990 {published data only}
    1. Ibrahim S, Derde MP, Kaufman L, Clerckx-Braun F, Jacqmin P, Brulein V, et al. Safety, pharmacokinetics and efficacy of once-a-day netilmicin and amikacin versus their conventional schedules in patients suffering from pelvic inflammatory disease. Renal Failure 1990;12(3):199-203. - PubMed
Jemsek 1997 {published data only}
    1. Jemsek JG, Harrison F. Ampicillin/sulbactam vs. cefoxitin for the treatment of pelvic inflammatory disease. Infectious Diseases in Obstetrics and Gynecology 1997;5(5):319-25. - PMC - PubMed
Jordheim 1974 {published data only}
    1. Jordheim O. Pivampicillin treatment of urogenital infections in gynaecological patients. Clinical evaluation. Infection 1974;2(3):142-4. - PubMed
Judlin 1995 {published data only}
    1. Judlin P, Koebele A, Zaccabri A, Walleghen E, Pavis A, Badonnel Y, et al. Comparative study of ofloxacin+amoxicillin-clavulanic acid versus doxycycline+amoxicillin-clavulanic acid combination in the treatment of pelvic Chlamydia trachomatis infections [Etude comparative des associations ofloxacine+amoxicilline-acide clavulanique versus doxycycline+amoxicilline-acide clavulanique dans le traitment des infections génitales hautes à Chlamydia Trachomatis]. Journal de Gynecologie Obstetrique et Biologie de la Reproduction 1995;24(3):253-9. - PubMed
Knuppel 1988 {published data only}
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Kosseim 1991 {published data only}
    1. Kosseim M, Rondald A, Plummer FA, D'Costa L, Brunham RC. Treatment of acute pelvic inflammatory disease in the ambulatory setting: trial of cefoxitin and doxycycline versus ampicillin-sulbactam. Antimicrobial Agents and Chemotherapy 1991;35(8):1651-6. - PMC - PubMed
Kotoulas 1992 {published data only}
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Kunzig 1990 {published data only}
    1. Kunzig HJ, Petersen EE, Hoyme UB, Martius J, Busch W. Sequential therapy with ciprofloxacin i.v./p.o. and metronidazole compared with cefotiam and metronidazole in the treatment of gynecological infections. Chemotherapy 1990;3(4):225-8.
Kvile 1980 {published data only}
    1. Kvile G, Langeland P, Norling B. Treatment of salpingitis with pivampicillin. A comparison of twice-daily and thrice-daily dosages. Infection 1980;8(1):32-6. - PubMed
Larsen 1986 {published data only}
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Larsen 1992 {published data only}
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Livengood 1992 {published data only}
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Ma 2010 {published data only}
    1. Ma L, Zhang YZ, Zheng YL, Wang ZH, Xu YD, Kong LN. Multicenter randomized controlled clinical study on levornidazole and sodium chloride injection in the treatment of pelvic anaerobic infections [in Chinese]. Chinese Journal of Obstetrics & Gynecology 2010;45(10):754-6. - PubMed
Maggioni 1998 {published data only}
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Maki 1979 {published data only}
    1. Maki DG, Craig WA, Agger WA. A comparative clinical trial of sisomicin and gentamicin in major gram-negative infections. Infection 1979;7(Suppl 3):S298-300.
Mandell 1993 {published data only}
    1. Mandell LA, Turgeon PL, Ronalds AR, Canadian Clinical Trials Group. A prospective randomized trial of imipenem-cilastatin versus clindamycin/tobramycin in the treatment of intra-abdominal and pelvic infections. Canadian Journal of Infectious Diseases 1993;4(5):279-87. - PMC - PubMed
Marier 1982 {published data only}
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Marshall 1982 {published data only}
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Matsuda 1988 {published data only}
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Matsuda 1989 {published data only}
    1. Matsuda S, Shimizu T, Maki M, Chimura T, Yajima A, Takahashi K, et al. Comparative double-blind clinical trial of ceftibuten (7432-S) and bacampicillin (BAPC) against gynecological infections [in Japanese]. Chemotherapy 1989;37(Suppl 1):667-700.
Moghtadaei 2008a {published data only}
    1. Moghtadaei P, Sardari F, Esmaeilian S. Comparison of ceftriaxone plus weekly azithromycin or daily ofloxacin for outpatient treatment of pelvic inflammatory disease: a randomized clinical trial. Journal of Family and Reproductive Health 2008;2(2):87-93.
Moghtadaei 2008b {published data only}
    1. Moghtadaei P, Sardari F, Esmaeilian S. Comparison of ceftriaxone plus weekly azithromycin or daily ofloxacin for outpatient treatment of pelvic inflammatory disease: a randomized clinical trial. Journal of Family and Reproductive Health 2008;2(2):87-93.
NCT04031664 {unpublished data only}
    1. NCT04031664. A clinical study on Qianjin capsule of gynaecology combined with antibiotics for pelvic inflammatory diseases (damp-heat stasis and Qi deficiency syndrome). clinicaltrials.gov/ct2/show/NCT04031664 2019.
NCT04035785 {published data only}
    1. NCT04035785. A clinical study on Kangfu anti-inflammatory suppository of gynaecology combined with antibiotics for pelvic inflammatory diseases (evidence of dampness and heat accumulation): a randomized, double blind, parallel Control of positive drugs, multi-center clinical study. clinicaltrials.gov/ct2/show/study/NCT04035785.
Ness 2002 {published data only}
    1. Ness RB, Soper DE, Holley RL, Peipert J, Randall H, Sweet RL, et al. Effectiveness of inpatient and outpatient treatment strategies for women with pelvic inflammatory disease: results from the Pelvic Inflammatory Disease Evaluation and Clinical Health (PEACH) randomized trial. American Journal of Obstetric and Gynecology 2002;186(5):929-37. [PMID: ] - PubMed
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    1. Ness RB, Trautmann G, Richter HE, Randall H, Peipert JF, Nelson DB, et al. Effectiveness of treatment strategies of some women with pelvic inflammatory disease a randomized trial. Obstetrics and Gynaecology 2005;106(3):573-80. - PubMed
Nicolle 1986 {published data only}
    1. Nicolle LE, Harding GK, Louie TJ, Thomson MJ, Blanchard RJ. Cefoxitin plus tobramycin and clindamycin plus tobramycin. A prospective randomized comparison in the therapy of mixed aerobic/anaerobic infections. Archives of Surgery 1986;121(8):891-6. - PubMed
Paavonen 1985 {published data only}
    1. Paavonen J, Vesterinen E, Aantaa K, Räsänen J. Factors predicting abnormal hysterosalpingographic findings in patients treated for acute pelvic inflammatory disease. International Journal of Gynaecology and Obstetrics 1985;23(3):171-5. - PubMed
Pastorek 1985 {published data only}
    1. Pastorek JG Jr, Aldridge KE, Cunningham GL, Faro S, Graffeo S, McNeeley GS, et al. Comparison of ticarcillin plus clavulanic acid with cefoxitin in the treatment of female pelvic infection. American Journal of Medicine 1985;29(79):161-3. - PubMed
Roy 1998 {published data only}
    1. Roy S, Koltun W, Chatwani A, Martens MG, Dittrich R, Luke DR. Treatment of acute gynecologic infections with trovafloxacin. Trovafloxacin Surgical Group. American Journal of Surgery 1998;178(6A Suppl):67S-73S. - PubMed
Ruiz Conde 1999 {published data only}
    1. Ruiz Conde MA, Grupo de Estudio Multicêntrico. Comparative multicenter study between meropenem versus clindamycin with gentamicin for the treatment of inpatient with obstetrics and/or gynecologic infections [Estudio multicéntrico comparativo entre meropenem y la asociación clindamicina-gentamicina en el tratamentiento de infecciones obstétricas y/o ginecológicas en pacientes hospitalizadas]. Clinica e Investigacion en Ginecologia y Obstetricia 1999;26(5):202-7.
Sanfilippo 1989 {published data only}
    1. Sanfilippo JS, Schikler KN. Mezlocillin versus penicillin and tobramycin in adolescent pelvic inflammatory disease: a prospective study. Internal Pediatrics 1989;4:53-6.
Schnider 1979 {published data only}
    1. Schnider G, Birken RA, Poindexter AN. A comparison of netilmicin and gentamicin in the treatment of pelvic infections. Obstetrics & Gynecology 1979;54(5):554-7. - PubMed
Senft 1986 {published data only}
    1. Senft HH, Stiglmayer R, Eibach HW, Koerner H. Sulbactam/ampicillin versus cefoxitin in the treatment of obstetric and gynaecological infections. Drugs 1986;31(Suppl 2):18-21. - PubMed
Sesti 1990 {published data only}
    1. Sesti F, Farnè C, Piccione E. Medical treatment of pelvic inflammatory disease. A clinical study on the therapeutic effectiveness of piperacillin + erythromycin and of piperacillin + clindamycin + gentamycin [Trattamento medico della malattia infiammatoria pelvica. studio clinico sull'efficacia terapeutica de piperacillina + eritromicina e di piperacillina + clindamicina + gentamicina]. La Clinica Terapeutica 1990;132(1):41-4. - PubMed
Sharma 2007 {published data only}
    1. Sharma JB, Chanana C, Sunesh K, Roy K, Malhotra N. Comparison of ofloxacin and ornidazole with probiotic versus doxycycline and metronidazole for the outpatient treatment of pelvic inflammatory disease. JK Science 2007;9(2):66-9.
Silva 1990 {published data only}
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Skerk 2003 {published data only}
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Spence 1981 {published data only}
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Stamm 1984 {published data only}
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Sweet 1988 {published data only}
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Thompson 1985 {published data only}
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Tulkens 1991 {published data only}
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References to other published versions of this review

Savaris 2012
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