RCOG. Management of Acute Pelvic Inflammatory Disease. Green Top Guideline No.32. Royal College of Obstetricians & Gynaecologists. 2008. http://www.rcog.org.uk/womens-health/clinical-guidance/acute-pelvic-inflammatory-disease-pid Accessed 23.09.14. RATIONALE: Recommended regimens: the recommended regimens are broad spectrum to cover N. gonorrhoea, C. trachomatis, and anaerobes. For outpatient management, either ofloxacin plus metronidazole for 14 days, or a stat dose of IM cefuroxime plus metronidazole and doxycycline for 14 days are recommended. Broad-spectrum treatment is warranted in PID because of the consequences of untreated infection (ectopic pregnancy, infertility, pelvic pain). Cefoxitin has a better evidence base for the treatment of PID than ceftriaxone, but it is not readily available in the UK. Ceftriaxone is therefore recommended. Although the combination of doxycycline and metronidazole (without IM ceftriaxone) has previously been
used in the UK to treat PID, there are no clinical trials that adequately assess its effectiveness and its use is not recommended.

BASH. UK National Guideline for the management of PID. British Association for Sexual Health and HIV. 2005. http://www.bashh.org/documents/118/118.pdf Accessed 23.09.14. RATIONALE: Recommended regimens: the recommended regimens for outpatient management are either ofloxacin plus metronidazole for 14 days, or a stat dose of IM cefuroxime plus metronidazole and doxycycline for 14 days. Ofloxacin should be avoided in women who are at high risk of gonococcal PID, because of increasing quinolone resistance in the UK. Treatment of partners: partners should be screened for gonorrhoea and chlamydia.

GRASP Steering Group. GRASP 2008 report: trends in antimicrobial resistant gonorrhoea. Health Protection Agency. 2009. http://webarchive.nationalarchives.gov.uk/20140714084352/http://www.hpa.org.uk/NewsCentre/NationalPressReleases/2012PressReleases/120912Gonorrhoeatreatmentresistanceriskfalls/ Accessed 23.09.14. RATIONALE: Ciprofloxacin resistance is now endemic in England and Wales, accounting for 28% of all gonorrhoea isolates tested in 2008. Public Health England and the British Infection Association had said that, for practical issues of administration in primary care, a stat dose of oral cefixime 400mg could be substituted for IM ceftriaxone. However, resistance to cephalosporins is increasing and treatment failures have been reported with cefixime; therefore, if gonorrhoea is suspected, IM ceftriaxone is the cephalosporin of choice.

Meads C, Knight T, Hyde C and Wilson J. The clinical effectiveness and cost-effectiveness of antibiotic regimens for pelvic inflammatory disease. West Midlands Health Technology Assessment group. 2004. www.rep.bham.ac.uk Accessed 23.09.14. RATIONALE: This systematic review identified 34 trials of antibiotic treatment for PID. Most studies were small, open-label, and of poor methodological study. One small trial was found that compared oral ofloxacin plus metronidazole with clindamycin plus gentamicin. The cure rate was 15/15 for ofloxacin plus metronidazole plus 17/18 for clindamycin plus gentamicin. The systematic review found one trial of ceftriaxone plus doxyxcyline was found, two trials of cefoxitin plus probenecid and doxycycline, and three trials of cefoxitin plus doxycycline compared to other antibiotics. Meta-analysis of these six studies found no difference in cure rates between IM cephalosporin plus doxycycline and the comparator antibiotics.

Ison CA, Mouton JW, Jones K. Which cephalosporin for gonorrhoea? Sex Transm Infect 2004;80:386-88. * RATIONALE: This study used previously published pharmacokinetic data on cefixime, ceftriaxone and cefuroxime to model the length of time tissue concentrations to these drugs would be above the MIC 90 (concentration needed to kill 90% of gonorrhoea isolates). Cefuroxime concentrations are too low. Ceftriaxone attains the optimal concentrations to prevent the development of step-wise mutations and resistance in* Neisseria gonorrhoea.

Ross JDC, Cronjé HS, Paszkowski T, Rakoczi I. Moxifloxacin versus ofloxacin plus metronidazole in uncomplicated pelvic inflammatory disease: results of a multicentre, double blind, randomised trial. Sex Transm Infect 2006;82(6):446-51. RATIONALE: This trial in 564 patients with uncomplicated PID in hospitals from 13 countries, compared oral metronidazole 500mg twice daily with either oral ofloxacin 400mg twice daily or moxifloxacin 400mg once daily. Clinical resolution with both regimens was 90% and bacteriological cure was similar. Metronidazole is included in the regimen to improve the coverage for anaerobic bacteria. Anaerobes are of relatively greater importance in patients with severe PID. Ofloxacin and moxifloxacin should be avoided in patients who are at high risk of gonococcal PID because of increasing quinolone resistance in the UK (e.g. when the patient‟s partner has gonorrhoea, in clinically severe disease, following sexual contact abroad). Quinolones should also be avoided as first line empirical treatment for PID in areas where >5% of PID is caused by quinolone resistant Neisseria gonorrhoea.

The POCAST project is funded by the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Healthcare Associated Infections and Antimicrobial Resistance at Imperial College London and by the Imperial College Healthcare Charity (Grant Ref No:7006/P36U).