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. 2008 Mar 10;2008:1606.

Pelvic inflammatory disease

Jonathan D C Ross 1
PMCID: PMC2907941  PMID: 19450319

Abstract

Introduction

Pelvic inflammatory disease is caused by infection of the upper female genital tract and is often asymptomatic. Pelvic inflammatory disease is the most common gynaecological reason for admission to hospital in the USA and is diagnosed in almost 2% of women aged 16 to 45 years consulting their GP in England and Wales.

Methods and outcomes

We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of empirical treatment compared with treatment delayed until the results of microbiological investigations are known? How do different antimicrobial regimens compare? What are the effects of routine antibiotic prophylaxis to prevent pelvic inflammatory disease before intrauterine contraceptive device (IUD) insertion? We searched: Medline, Embase, The Cochrane Library, and other important databases up to May 2007 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).

Results

We found nine systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.

Conclusions

In this systematic review, we present information relating to the effectiveness and safety of the following interventions: antibiotics (oral, parenteral, empirical treatment, treatment guided by test results, different durations, outpatient, inpatient), and routine antibiotic prophylaxis (before intrauterine device insertion in women at high risk or low risk).

Key Points

Pelvic inflammatory disease (PID) is caused by infection of the upper female genital tract, and is often asymptomatic.

  • PID is the most common gynaecological reason for admission to hospital in the USA, and is diagnosed in almost 2% of women aged 16 to 45 years consulting their GP in England and Wales.

  • Epithelial damage from infections such as Chlamydia trachomatis or Neisseria gonorrhoeae can allow opportunistic infection from many other bacteria.

  • About 20% of women with PID become infertile, 40% develop chronic pain, and 1% of women who conceive have an ectopic pregnancy.

  • Spontaneous resolution of symptoms may occur in some women, but early initiation of treatment is needed to prevent impairment of fertility.

As there are no reliable signs and symptoms of PID, empirical treatment is common.

  • The positive predictive value of clinical diagnosis is 65% to 90% compared with laparoscopy, and observational studies suggest that delaying treatment by 3 days can impair fertility.

  • The absence of infection from the lower genital tract does not exclude a diagnosis of PID.

Oral antibiotics are likely to be beneficial, and are associated with the resolution of symptoms and signs of pelvic infection, but we don't know which antibiotic regimen is best.

  • Clinical and microbiological cure rates of 88% to 100% have been reported after oral antibiotic treatment.

  • The risks of tubal occlusion and infertility depend on severity of infection before treatment. Clinical improvement may not necessarily translate into improved fertility.

Oral antibiotics may be as effective as parenteral antibiotics in reducing symptoms and preserving fertility, with fewer adverse effects, and outpatient treatment is as effective as inpatient treatment for uncomplicated PID. However, we don't know the optimal duration of treatment.

Risks of PID may be increased after instrumentation of the cervix, and testing for infection before such procedures is advisable, but we don't know whether prophylactic antibiotics before IUD insertion reduce these risks.

About this condition

Definition

Pelvic inflammatory disease (PID) is inflammation and infection of the upper genital tract in women, typically involving the fallopian tubes, ovaries, and surrounding structures.

Incidence/ Prevalence

The exact incidence of PID is unknown, because the disease cannot be diagnosed reliably from clinical symptoms and signs. Direct visualisation of the fallopian tubes by laparoscopy is the best single diagnostic test, but it is invasive, lacks sensitivity, and is not used routinely in clinical practice. PID is the most common gynaecological reason for admission to hospital in the USA, accounting for 18/10,000 recorded hospital discharges. A diagnosis of PID is made in 1/62 (1.6%) women aged 16 to 45 years attending their primary-care physician in England and Wales. However, because most PID is asymptomatic, this figure underestimates the true prevalence. A crude marker of PID in resource-poor countries can be obtained from reported hospital admission rates, where it accounts for 17% to 40% of gynaecological admissions in sub-Saharan Africa, 15% to 37% in Southeast Asia, and 3% to 10% in India.

Aetiology/ Risk factors

Factors associated with PID mirror those for STDs — young age, reduced socioeconomic circumstances, lower educational attainment, and recent new sexual partner. Infection ascends from the cervix, and initial epithelial damage caused by bacteria (especially Chlamydia trachomatis and Neisseria gonorrhoeae) allows the opportunistic entry of other organisms. Many different microbes, including Mycoplasma genitalium and anaerobes, may be isolated from the upper genital tract. The spread of infection to the upper genital tract may be increased by instrumentation of the cervix, but reduced by barrier methods of contraception, levonorgestrel implants, and by oral contraceptives compared with other forms of contraception.

Prognosis

PID has a high morbidity; about 20% of affected women become infertile, 40% develop chronic pelvic pain, and 1% of those who conceive have an ectopic pregnancy (see table 1 ). Uncontrolled observations suggest that clinical symptoms and signs resolve in a significant proportion of untreated women. Repeated episodes of PID are associated with a four- to sixfold increase in the risk of permanent tubal damage. One case control study (76 cases and 367 controls) found that delaying treatment by 3 or more days is associated with impaired fertility (OR 2.6, 95% CI 1.2 to 5.9).

Table 1.

RCTs comparing outpatient versus inpatient antibiotic treatment for PID at different follow-up periods (see text).

Ref Population Recurrence Chronic pelvic pain Infertility Ectopic pregnancy
  831 women with mild to moderate PID; 808 followed up to 35 months; inpatients v outpatients 12% v 17%; OR 0.69, 95% CI 0.43 to 1.09 34% v 30%; OR 1.24, 95% CI 0.87 to 1.77 18.4% v 17.9%; OR 1.32, 95% CI 0.86 to 2.04 1.0% v 0.3%; OR 3.66, 95% CI 0.40 to 33.12
  As above; 541 followed up to 84 months; inpatients v outpatients 18% v 24%; OR 0.71, 95% CI 0.48 to 1.05 41% v 45%; OR 1.21, 95% CI 0.87 to 1.67 17% v 21%; OR 0.88, 95% CI 0.59 to 1.32 1.2% v 0.2%; OR 4.91, 95% CI 0.57 to 42.25
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PID, pelvic inflammatory disease

Aims of intervention

To alleviate the pain and systemic malaise associated with infection; to achieve microbiological cure; to prevent development of permanent tubal damage with associated sequelae, such as chronic pelvic pain, ectopic pregnancy, and infertility; and to prevent the spread of infection to others, with minimal adverse effects.

Outcomes

Cure rate (includes clinical cure rate; microbiological cure of the upper genital tract; resolution of acute symptoms and signs); symptom severity (includes reduction of chronic pelvic pain); rate of ectopic pregnancy; fertility (includes pregnancy [other than ectopic]); rate of transmission to others; recurrence; quality of life; and adverse effects of treatment; in question on routine antibiotic prophylaxis: rate of PID.

Methods

Clinical Evidence search May 2007. The following databases were used to identify studies for this systematic review: Medline 1966 to May 2007, Embase 1980 to May 2007, and The Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Clinical Trials 2007, Issue 2. Additional searches were carried out using these websites: NHS Centre for Reviews and Dissemination (CRD) — for Database of Abstracts of Reviews of Effects (DARE) and Health Technology Assessment (HTA), Turning Research into Practice (TRIP), and NICE. We also searched for retractions of studies included in the review. Abstracts of the studies retrieved from the initial search were assessed by an information specialist. Selected studies were then sent to the author for additional assessment, using predetermined criteria to identify relevant studies. Study-design criteria for inclusion in this review were: published systematic reviews and RCTs in any language, at least single blinded, and containing more than 20 individuals of whom more than 80% were followed up. There was no minimum length of follow-up required to include studies. We excluded all studies described as “open”, “open label”, or not blinded unless blinding was impossible. We also searched for cohort studies on IUD insertion risk/harms. In addition we use a regular surveillance protocol to capture harms alerts from organisations such as the FDA and the UK Medicines and Healthcare products Regulatory Agency (MHRA), which are added to the reviews as required. To aid readability of the numerical data in our reviews, we round many percentages to the nearest whole number. Readers should be aware of this when relating percentages to summary statistics such as relative risks (RRs) and odds ratios (ORs). We have performed a GRADE evaluation of the quality of evidence for interventions included in this review (see table). The categorisation of the quality of the evidence (high, moderate, low, or very low) reflects the quality of evidence available for our chosen outcomes in our defined populations of interest. These categorisations are not necessarily a reflection of the overall methodological quality of any individual study, because the Clinical Evidence population and outcome of choice may represent only a small subset of the total outcomes reported, and population included, in any individual trial. For further details of how we perform the GRADE evaluation and the scoring system we use, please see our website (www.clinicalevidence.com).

Table.

GRADE Evaluation of interventions for Pelvic inflammatory disease.

Important outcomes Cure rate, Fertility, Quality of life, Rate of ectopic pregnancy, Rate of PID, Rate of transmission to others, Recurrence, Symptom severity
Studies (Participants) Outcome Comparison Type of evidence Quality Consistency Directness Effect size GRADE Comment
How do different antimicrobial regimens compare when treating women with confirmed pelvic inflammatory disease?
at least 35 RCTs (at least 4289 women) Cure rate Different antibiotics versus each other 4 –2 0 –1 0 Very low Quality points deducted for inclusion of observational studies and for poor quality studies. Directness point deducted for differences in disease severity
2 (321) Cure rate Oral antibiotics versus parenteral antibiotics 4 –1 0 –1 0 Low Quality point deducted for incomplete reporting of results. Directness point deducted for inclusion of oral antibiotics in parenteral arm
1 (831) Symptom severity Oral antibiotics versus parenteral antibiotics 4 –1 0 –1 0 Low Quality point deducted for no statistical assessment. Directness point deducted for inclusion of intramuscular injection in outpatient arm and oral antibiotics in parenteral arm
1 (831) Rate of ectopic pregnancy Oral antibiotics versus parenteral antibiotics 4 –1 0 –1 0 Low Quality point deducted for no statistical assessment. Directness point deducted for inclusion of intramuscular injection in outpatient arm
1 (831) Fertility Oral antibiotics versus parenteral antibiotics 4 –1 0 –1 0 Low Quality point deducted for no statistical assessment for some outcomes. Directness point deducted for inclusion of intramuscular injection in outpatient arm
1 (831) Recurrence Oral antibiotics versus parenteral antibiotics 4 –1 0 –1 0 Low Quality point deducted for no statistical assessment. Directness point deducted for inclusion of intramuscular injection in outpatient arm
What are the effects of routine antibiotic prophylaxis to prevent pelvic inflammatory disease before IUD insertion?
4 (3598) Rate of PID Antibiotic prophylaxis before IUD insertion versus no antibiotic prophylaxis (in women at low risk) 4 –1 0 0 0 Moderate Quality point deducted for incomplete reporting of results
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We initially allocate 4 points to evidence from RCTs, and 2 points to evidence from observational studies. To attain the final GRADE score for a given comparison, points are deducted or added from this initial score based on preset criteria relating to the categories of quality, directness, consistency, and effect size. Quality: based on issues affecting methodological rigour (e.g., incomplete reporting of results, quasi-randomisation, sparse data [<200 people in the analysis]). Consistency: based on similarity of results across studies. Directness: based on generalisability of population or outcomes. Effect size: based on magnitude of effect as measured by statistics such as relative risk, odds ratio, or hazard ratio.

Glossary

Low-quality evidence

Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.

Moderate-quality evidence

Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.

Very low-quality evidence

Any estimate of effect is very uncertain.

Disclaimer

The information contained in this publication is intended for medical professionals. Categories presented in Clinical Evidence indicate a judgement about the strength of the evidence available to our contributors prior to publication and the relevant importance of benefit and harms. We rely on our contributors to confirm the accuracy of the information presented and to adhere to describe accepted practices. Readers should be aware that professionals in the field may have different opinions. Because of this and regular advances in medical research we strongly recommend that readers' independently verify specified treatments and drugs including manufacturers' guidance. Also, the categories do not indicate whether a particular treatment is generally appropriate or whether it is suitable for a particular individual. Ultimately it is the readers' responsibility to make their own professional judgements, so to appropriately advise and treat their patients.To the fullest extent permitted by law, BMJ Publishing Group Limited and its editors are not responsible for any losses, injury or damage caused to any person or property (including under contract, by negligence, products liability or otherwise) whether they be direct or indirect, special, incidental or consequential, resulting from the application of the information in this publication.

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BMJ Clin Evid. 2008 Mar 10;2008:1606.

Empirical antibiotic treatment

Summary

We found no clinically important results from RCTs about empirical antibiotic treatment (before receiving results of microbiological tests) compared with treatment guided by test results in women with suspected PID.

As there are no reliable signs and symptoms of PID, empirical treatment is common.

The positive predictive value of clinical diagnosis is 65% to 90% compared with laparoscopy, and observational studies suggest that delaying treatment by 3 days can impair fertility.

Benefits and harms

Empirical antibiotic treatment versus delayed treatment in women with suspected PID:

We found no systematic review or RCTs comparing empirical versus delayed treatment (see comment).

Further information on studies

None.

Comment

Clinical guide:

Because there are no reliable clinical diagnostic criteria for pelvic inflammatory disease (PID), early empirical treatment is common. The positive predictive value of a clinical diagnosis is 65% to 90% compared with laparoscopy. The absence of infection from the lower genital tract, where samples are usually taken, does not exclude PID, and so may not influence the decision to treat. One case control study (76 cases and 367 controls) found that delaying treatment by 3 or more days is associated with impaired fertility (OR 2.6, 95% CI 1.2 to 5.9).

Substantive changes

No new evidence

BMJ Clin Evid. 2008 Mar 10;2008:1606.

Antibiotics (for symptoms and microbiological clearance in women with confirmed pelvic inflammatory disease)

Summary

There is consensus that antibiotic treatment is more effective than no treatment for women with confirmed PID.

Benefits and harms

Different antibiotics versus each other:

We found one systematic review (search date 2004, 34 RCTs, 3548 women) and one subsequent RCT assessing the effects of different antibiotic regimens in the treatment of pelvic inflammatory disease (PID). The review assessed standard antibiotic regimens and non-standard regimens; see table 2 for “standard” and non-standard regimens as defined by the review. The review identified no RCTs comparing standard or non-standard regimens versus placebo (see comment).

Table 1.

Standard antibiotic regimens and corresponding trial evidence (see text).

Regimen Trial evidence available
Oral ofloxacin 800 mg daily plus oral metronidazole 800 g daily for 14 days Ofloxacin plus metronidazole v clindamycin plus gentamicin
im ceftriaxone 250 mg once or im cefoxitin 2 g once plus oral probenecid 1 g once followed by oral doxycycline 200 mg daily plus oral metronidazole 800 mg daily for 14 days Cefoxitin plus doxycycline v cefoxitin plus probenecid plus doxycycline
im ceftriaxone 250 mg or im cefoxitin 2 g plus oral probenecid 1 g or a third-generation cephalosporin plus oral doxycycline 200 mg for 14 days Ceftriaxone or cefoxitin plus oral probenecid or a third-generation cephalosporin plus oral doxycycline v non-standard treatments
iv cefoxitin 6 g daily plus iv (or oral) doxycycline 200 mg daily followed by oral doxycycline 200 mg daily plus oral metronidazole 800 mg daily to complete 14 days Cefoxitin plus doxycycline v clindamycin plus gentamicin, cefoxitin plus doxycycline v cefoxitin plus probenecid plus doxycycline
iv clindamycin 2.7 g daily plus iv gentamicin 2 mg/kg loading dose then 4.5 mg/kg daily followed by either oral doxycycline 200 mg daily plus oral metronidazole 200 mg daily or oral clindamycin 1.8 g daily to complete 14 days Ofloxacin plus metronidazole v clindamycin plus gentamicin, cefoxitin plus doxycycline v clindamycin plus gentamicin, iv clindamycin plus gentamicin followed by either oral doxycycline plus oral metronidazole or oral clindamycin v non-standard treatments
iv ofloxacin 800 mg daily plus iv metronidazole 1.5 g daily for 14 days Ofloxacin plus metronidazole v clindamycin plus gentamicin
iv ciprofloxacin 400 mg daily plus iv (or oral) doxycycline 200 mg daily plus iv metronidazole 1.5 g daily (unspecified length, presume 14 days) No RCT comparisons
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im, intramuscular; iv, intravenous

Cure rate

Different antibiotics compared with each other We don’t know how different antibiotic regimens compare with each other at improving cure rates in women with confirmed pelvic inflammatory disease (PID) (very low-quality evidence).

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Cure rate

RCT		 33 women
In review 		Cure rate
15/15 (100%) with ofloxacin (oral then iv) plus metronidazole
7/18 (39%) with clindamycin plus gentamicin
RR 1.06
95% CI 0.95 to 1.18
The review reported that overall trial quality was poor 		Not significant

RCT		 115 women
In review 		Cure rate
46/55 (84%) with cefoxitin plus doxycycline
52/60 (87%) with clindamycin plus gentamicin
RR 0.97
95% CI 0.83 to 1.12
The review reported that overall trial quality was poor 		Not significant

RCT		 198 women
In review 		Cure rate
75/94 (80%) with cefoxitin plus doxycycline
87/104 (84%) with clindamycin plus gentamicin
RR 0.95
95% CI 0.84 to 1.09
The review reported that overall trial quality was poor 		Not significant

RCT		 130 women
In review 		Cure rate
64/67 (96%) with cefoxitin plus doxycycline
57/63 (90%) with clindamycin plus gentamicin
RR 1.06
95% CI 0.96 to 1.16
Overall effect size
RR 1.01
95% CI 0.93 to 1.08
The review reported that overall trial quality was poor 		Not significant

RCT		 131 women
In review 		Cure rate
49/64 (77%) with ceftriaxone plus doxycycline
57/67 (85%) with ciprofloxacin plus clindamycin
RR 0.90
95% CI 0.76 to 1.07
The review reported that overall trial quality was poor 		Not significant

RCT		 148 women
In review 		Cure rate
73/75 (97%) with cefoxitin plus doxycycline
70/73 (96%) with clindamycin plus tobramycin
RR 1.02
95% CI 0.96 to 1.08
The review reported that overall trial quality was poor 		Not significant

RCT		 249 women
In review 		Cure rate
75/121 (62%) with cefoxitin plus probenecid plus doxycycline
80/128 (63%) with ofloxacin
RR 0.99
95% CI 0.82 to 1.20
The review reported that overall trial quality was poor 		Not significant

RCT		 62 women
In review 		Cure rate
30/31 (97%) with cefoxitin plus doxycycline
28/31 (90%) with clindamycin plus amikacin
RR 1.07
95% CI 0.94 to 1.22
The review reported that overall trial quality was poor 		Not significant

RCT		 79 women
In review 		Cure rate
38/40 (95%) with cefoxitin plus doxycycline
36/39 (92%) with clindamycin plus tobramycin
RR 1.03
95% CI 0.98 to 1.08
The review reported that overall trial quality was poor 		Not significant

RCT		 72 women
In review 		Cure rate
34/35 (97%) with cefoxitin plus probenecid plus doxycycline
35/37 (95%) with ofloxacin
RR 1.03
95% CI 0.93 to 1.13
Overall effect size
RR 1.02
95% CI 0.97 to 1.06
The review reported that overall trial quality was poor 		Not significant

RCT		 25 women
In review 		Cure rate
13/15 (87%) with clindamycin plus gentamicin
10/10 (100%) with ciprofloxacin
RR 0.87
95% CI 0.71 to 1.06
The review reported that overall trial quality was poor 		Not significant

RCT		 76 women
In review 		Cure rate
38/40 (95%) with clindamycin plus gentamicin
33/36 (92%) with ceftazidime plus doxycycline
RR 1.04
95% CI 0.92 to 1.17
The review reported that overall trial quality was poor 		Not significant

RCT		 68 women
In review 		Cure rate
34/35 (97%) with clindamycin plus gentamicin
33/33 (100%) with ciprofloxacin (plus clindamycin in one women)
RR 0.97
95% CI 0.92 to 1.03
The review reported that overall trial quality was poor 		Not significant

RCT		 84 women
In review 		Cure rate
40/40 (100%) with clindamycin plus gentamicin
41/44 (93%) with meropenem
RR 1.07
95% CI 0.99 to 1.16
The review reported that overall trial quality was poor 		Not significant

RCT		 13 women
In review 		Cure rate
8/8 (100%) with clindamycin plus gentamicin
5/5 (100%) with aztreonam plus clindamycin
Significance not assessed
The review reported that overall trial quality was poor

RCT		 77 women
In review 		Cure rate
39/40 (98%) with clindamycin plus gentamicin plus doxycycline
37/37 (100%) with imipenem plus cilastin (plus doxycycline in some women)
RR 0.98
95% CI 0.93 to 1.02
The review reported that overall trial quality was poor 		Not significant

RCT		 58 women
In review 		Cure rate
21/29 (72%) with clindamycin plus gentamicin
23/29 (79%) with cefotaxime
RR 0.91
95% CI 0.68 to 1.22
The review reported that overall trial quality was poor 		Not significant

RCT		 30 women
In review 		Cure rate
14/14 (100%) with clindamycin plus gentamicin
15/16 (94%) with ciprofloxacin
RR 0.98
95% CI 0.90 to 1.07
Overall effect size
RR 1.00
95% CI 0.96 to 1.04
The review reported that overall trial quality was poor 		Not significant

RCT		 81 women
In review 		Cure rate
10/42 (24%) with amoxicillin/clavulanate
9/39 (25%) with amoxicillin plus aminoglycoside plus metronidazole
RR 1.03
95% CI 0.47 to 2.27
The review reported that overall trial quality was poor 		Not significant

RCT		 20 women
In review 		Cure rate
2/10 (20%) with ampicillin plus metronidazole
10/10 (100%) with doxycycline plus oxytetracycline/tetracycline plus metronidazole
RR 0.20
95% CI 0.06 to 0.69
The review reported that overall trial quality was poor 		Large effect size doxycycline plus oxytetracycline/tetracycline plus metronidazole

RCT		 44 women
In review 		Cure rate
20/22 (91%) with amoxicillin/clavulanate
19/22 (86%) with ampicillin (or amoxicillin) plus gentamicin plus metronidazole
RR 1.05
95% CI 0.85 to 1.30
The review reported that overall trial quality was poor 		Not significant

RCT		 60 women
In review 		Cure rate
28/30 (93%) with ampicillin
28/30 (93%) with cefoxitin
RR 1.00
95% CI 0.87 to 1.14
The review reported that overall trial quality was poor 		Not significant

RCT		 33 women
In review 		Cure rate
17/18 (94%) with doxycycline plus amoxicillin/clavulanate
15/15 (100%) with ofloxacin plus amoxicillin/clavulanate
RR 0.94
95% CI 0.84 to 1.06
The review reported that overall trial quality was poor 		Not significant

RCT		 47 women
In review 		Cure rate
22/23 (97%) with ampicillin
18/24 (75%) with doxycycline
RR 1.28
95% CI 1.00 to 1.63
Overall effect size
RR 1.05
95% CI 0.91 to 1.22
The review reported that overall trial quality was poor 		Not significant

RCT		 18 women
In review 		Cure rate
9/10 (90%) with ceftriaxone
8/8 (100%) with cefotaxime
RR 0.90
95% CI 0.73 to 1.11
The review reported that overall trial quality was poor 		Not significant

RCT		 34 women
In review 		Cure rate
14/16 (88%) with imipenem plus cilastatin
18/18 (100%) with meropenem
RR 0.88
95% CI 0.73 to 1.05
The review reported that overall trial quality was poor 		Not significant

RCT		 36 women
In review 		Cure rate
16/19 (84%) with cefoxitin
14/17 (82%) with cefotaxime
RR 1.02
95% CI 0.76 to 1.37
Overall effect size
RR 0.95
95% CI 0.87 to 1.04
The review reported that overall trial quality was poor 		Not significant

RCT		 64 women
In review 		Cure rate
42/44 (95%) with lymecycline
9/20 (45%) with clindamycin
RR 2.12
95% CI 1.30 to 3.46
The review reported that overall trial quality was poor 		Moderate effect size lymecycline

RCT		 9 women
In review 		Cure rate
4/4 (100%) with tobramycin plus metronidazole (spectinomycin)
5/5 (100%) with tobramycin plus clindamycin (spectinomycin)
Overall effect size
RR 0.95
RR 0.78 to 1.17
The review reported that overall trial quality was poor 		Not significant

RCT		 79 women
In review 		Cure rate
40/40 (100%) with azithromycin plus metronidazole
38/39 (97%) with azithromycin
RR 0.89
95% CI 0.50 to 1.57
The review reported that overall trial quality was poor 		Not significant

RCT		 36 women
In review 		Cure rate
14/20 (70%) with doxycycline plus metronidazole
15/16 (94%) with ciprofloxacin
RR 0.75
95% CI 0.55 to 1.02
Overall effect size
RR 0.80
95% CI 0.52 to 1.24
The review reported that overall trial quality was poor 		Not significant

RCT		 741 women with PID, without pelvic or tubo-ovarian abscess Resolution of signs and symptoms 5 to 24 days post-treatment
262/289 (90.7%) with ofloxacin plus metronidazole
248/275 (90.2%) with moxifloxacin alone
Difference +0.5%
95% CI –5.7% to +4.0%
The review reported that overall trial quality was poor 		Not significant
Open in a new tab

Symptom severity

No data from the following reference on this outcome.

Rate of ectopic pregnancy

No data from the following reference on this outcome.

Fertility

No data from the following reference on this outcome.

Recurrence

No data from the following reference on this outcome.

Rate of transmission to others

No data from the following reference on this outcome.

Quality of life

No data from the following reference on this outcome.

Adverse effects

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Adverse effects (global)

RCT		 138 women
In review 		Adverse effect (any)
52/69 (75%) with ceftriaxone plus doxycycline
57/69 (83%) with ciprofloxacin plus clindamycin
Significance not assessed

RCT		 272 women
In review 		Adverse effects (any)
20/134 (15%) with cefoxitin plus probenecid plus doxycycline
9/138 (7%) with ofloxacin
Significance not assessed

RCT		 72 women
In review 		Adverse effects (any)
9/35 (26%) with cefoxitin plus probenecid plus doxycycline
6/37 (26%) with ofloxacin
Significance not assessed

RCT		 81 women
In review 		Adverse effect (any)
5/42 (12%) with amoxicillin/clavulanate
2/39 (5%) with amoxicillin plus aminoglycoside plus metronidazole
Significance not assessed

RCT		 36 women
In review 		Adverse effect (any)
11/20 (55%) with doxycycline
3/16 (19%) with metronidazole
Significance not assessed

RCT		 213 women
In review 		Adverse effect (any)
32/107 (30%) with azithromycin plus metronidazole
26/106 (25%) with azithromycin
Significance not assessed

RCT		 170 women
In review 		Vestibular disturbance
0/82 (0%) with cefoxitin plus doxycycline
3/88 (3%) with clindamycin plus gentamicin
Significance not assessed

RCT		 120 women
In review 		Surgical intervention
1/60 (2%) with cefoxitin plus doxycycline
1/60 (2%) with clindamycin plus gentamicin
Significance not assessed
Withdrawal from treatment owing to adverse effects

RCT		 138 women
In review 		Withdrawal from treatment
1/69 (1%) with ceftriaxone plus doxycycline
1/69 (1%) with ciprofloxacin plus clindamycin
Significance not assessed

RCT		 80 women
In review 		Withdrew from study
0/40 (0%) with clindamycin plus gentamicin
0/40 (0%) with ceftazidime plus doxycycline
Significance not assessed

RCT		 120 women
In review 		Withdrew from study due to adverse effects
0/60 (0%) with cefoxitin plus doxycycline
1/60 (2%) with clindamycin plus gentamicin
Significance not assessed

RCT		 230 women
In review 		Withdrew from study due to adverse effects
1/114 (1%) with cefoxitin plus doxycycline
0/116 (0%) with clindamycin plus gentamicin
Significance not assessed

RCT		 81 women
In review 		Withdrawal from treatment due to adverse effects
0/42 (0%) with amoxicillin/clavulanate
1/39 (3%) with amoxicillin plus aminoglycoside plus metronidazole
Significance not assessed

RCT		 33 people
In review 		Withdrawal from treatment due to adverse effects
0/15 (0%) with amoxicillin/clavulanate
0/18 (0%) with ofloxacin
Significance not assessed

RCT		 36 women
In review 		Withdrawal from treatment due to adverse effects
0/20 (0%) with doxycycline
0/16 (0%) with metronidazole
Significance not assessed

RCT		 213 women
In review 		Withdrawn from treatment due to adverse effects
4/107 (4%) with azithromycin plus metronidazole
2/106 (2%) with azithromycin
Significance not assessed
Angio-oedema

RCT		 81 women
In review 		Angio-oedema
0/42 (0%) with amoxicillin/clavulanate
1/39 (3%) with amoxicillin plus aminoglycoside plus metronidazole
Significance not assessed
Allergy

RCT		 148 women
In review 		Rash
2/75 (3%) with cefoxitin plus doxycycline
1/75 (1%) with clindamycin plus tobramycin
Significance not assessed

RCT		 272 women
In review 		Rash
1/134 (0.7%) with cefoxitin plus probenecid plus doxycycline
2/138 (1.4%) with ofloxacin
Significance not assessed

RCT		 130 women
In review 		Mild rash
1/67(2%) with cefoxitin pus doxycycline
1/63 (2%) with clindamycin plus gentamicin
Significance not assessed

RCT		 72 women
In review 		Allergy
0/35 (0%) with cefoxitin plus probenecid plus doxycycline
1/37 (3%) with ofloxacin
Significance not assessed

RCT		 70 women
In review 		Allergies
0/35 (0%) with clindamycin plus gentamicin
2/35 (6%) with ciprofloxacin (plus clindamycin in 1 woman)
Significance not assessed 		Favoured intervention

RCT		 44 women
In review 		Cutaneous allergy
1/22 (5%) with amoxicillin/clavulanate
0/22 (0%) with ampicillin (or amoxicillin) plus gentamicin plus metronidazole
Significance not assessed

RCT		 230 women
In review 		Pruritus
2/114 (2%) with cefoxitin plus doxycycline
11/116 (9%) with clindamycin plus gentamicin
Significance not assessed
Gastrointestinal

RCT		 170 women
In review 		Gastrointestinal
10/82 (12%) with cefoxitin plus doxycycline
15/88 (17%) with clindamycin plus gentamicin
Significance not assessed

RCT		 741 women Gastrointestinal
54/378 (14%) with moxifloxacin
71/363 (20%) with ofloxacin plus metronidazole
P = 0.057 		Not significant

RCT		 130 women
In review 		Diarrhoea
2/67 (3%) with cefoxitin plus doxycycline
2/63 (3%) with clindamycin plus gentamicin
Significance not assessed

RCT		 272 women
In review 		Nausea/vomiting
19/134 (14%) with cefoxitin plus probenecid plus doxycycline
2/138 (1%) with ofloxacin
Significance not assessed

RCT		 72 women
In review 		Nausea/vomiting
3/35 (9%) with cefoxitin plus probenecid plus doxycycline
2/37 (5%) with ofloxacin
Significance not assessed
Headaches/insomnia

RCT		 272 women
In review 		Insomnia
0/134 (0%) with cefoxitin plus probenecid plus doxycycline
2/138 (1%) with ofloxacin
Significance not assessed

RCT		 72 women
In review 		Headaches
0/35 (0%) with cefoxitin plus probenecid plus doxycycline
1/37 (3%) with ofloxacin
Significance not assessed
Candidal vaginitis

RCT		 272 women
In review 		Candidal vaginitis
6/134 (4%) with cefoxitin plus probenecid plus doxycycline
5/138 (4%) with ofloxacin
Significance not assessed

RCT		 72 women
In review 		Candidal vaginitis
2/35 (6%) with cefoxitin plus probenecid plus doxycycline
1/37 (3%) with ofloxacin
Significance not assessed
Severe adverse effects

RCT		 213 women
In review 		Severe adverse effects
8/107 (7%) with azithromycin plus metronidazole
2/106 (2%) with azithromycin
Significance not assessed
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Further information on studies

The review included women who had been either: diagnosed clinically or laparoscopically with PID; treated with any antibiotic combination; and with an outcome measure of clinical care, microbiological care, infertility, ectopic pregnancy, chronic pelvic pain, or any other relevant outcome. The review made no distinction for severity of disease or between intravenous and oral treatment.

Comment

We found one systematic review (search date 1992, 21 studies), which reported on clinical and microbiological cure rates for various antibiotic regimens in the treatment of pelvic inflammatory disease (PID; see table 3 ). The review provided aggregated data on indirect comparisons; aspects of the review were subsequently updated (search date 1997, 26 studies, 1925 women). The earlier version of the review examined all antimicrobial regimens, whereas the updated version focused on anti-anaerobic treatment. The identified studies included case series, and it is not possible to ascertain from the aggregated data published how many studies were RCTs. Inclusion criteria were a diagnosis of PID (clinical, microbiological, laparoscopic, or by endometrial biopsy) and microbiological testing for Chlamydia trachomatis and Neisseria gonorrhoeae. The review found that antibiotics were effective in relieving the symptoms associated with PID, with clinical and microbiological cure rates of 88% to 100% (see table 2 ). The only regimen that seemed to perform less well was oral metronidazole plus doxycycline. However, the studies were of low power, and apparent differences in efficacy may have been confounded by differences in disease severity among studies.

Table 1.

Cure rates for the antibiotic treatment of acute PID: aggregated data from a systematic review of RCTs and case series (see text).

Drug regimen Number of studies Number of women Cure rate (%)
      Clinical Microbiological*
Inpatient treatment (initially parenteral switching to oral)
Clindamycin plus aminoglycoside 11 470 91 97
Cefoxitin plus doxycycline 8 427 91 98
Cefotetan plus doxycycline 3 174 95 100
Ceftizoxime plus tetracycline 1 18 88 100
Cefotaxime plus tetracycline 1 19 94 100
Ciprofloxacin 4 90 94 96
Ofloxacin 1 36 100 97
Sulbactam/ampicillin plus doxycycline 1 37 95 100
Co-amoxiclav 1 32 93 –
Metronidazole plus doxycycline 2 36 75 71
Outpatient treatment (oral unless indicated otherwise)
Cefoxitin (im) plus probenecid plus doxycycline 3 219 89 93
Ofloxacin 2 165 95 100
Co-amoxiclav 1 35 100 100
Sulbactam/ampicillin 1 36 70 70
Ceftriaxone (im) plus doxycycline 1 64 95 100
Ciprofloxacin plus clindamycin 1 67 97 94
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*Neisseria gonorrhoeae, Chlamydia trachomatis, or both, when detected in lower genital tract; im, intramuscular; PID, pelvic inflammatory disease

Clinical guide:

We found no RCTs comparing antibiotics versus placebo or no treatment. However, such trials would be considered unethical, because there is strong consensus that antibiotic treatments are more effective in women with pelvic inflammatory disease (PID) than no treatment. We found little evidence about treatment of PID of differing severity, the effect of ethnicity, or the effects of tracing sexual contacts (see review on partner notification). The risks of tubal occlusion and of subsequent infertility relate to the severity of PID before starting treatment, and clinical improvement may not translate into preserved fertility. The inclusion of observational studies in the older systematic review without a sensitivity analysis may compromise the validity of the conclusions. In the review, reliable comparison of different drugs may be confounded by possible differences in disease severity among the included studies.

Substantive changes

Antibiotics (for symptoms and microbiological clearance in women with confirmed pelvic inflammatory disease) One RCT added; benefits and harms data enhanced, categorisation unchanged (Likely to be beneficial).

BMJ Clin Evid. 2008 Mar 10;2008:1606.

Oral antibiotics versus parenteral antibiotics

Summary

Oral antibiotics may be as effective as parenteral antibiotics in reducing symptoms and preserving fertility, with fewer adverse effects, and outpatient treatment seems as effective as inpatient treatment for uncomplicated PID. However, we don't know the optimal duration.

Benefits and harms

Oral antibiotics versus parenteral antibiotics:

We found one systematic review containing three RCTs that compared oral versus parenteral antibiotic treatment.

Cure rate

Oral antibiotics compared with parenteral antibiotics Oral antibiotics and parenteral antibiotics may be equally effective at improving cure rate in women with uncomplicated pelvic inflammatory disease (PID) (moderate-quality evidence).

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Cure rate

RCT		 249 women with uncomplicated pelvic inflammatory disease (outpatient setting)
In review 		Cure rate
with oral ofloxacin
with parenteral cefoxitin plus oral doxycycline
Absolute results not reported
RR 1.03
95% CI 0.97 to 1.10 		Not significant

RCT		 72 women with uncomplicated acute salpingitis (outpatient setting)
In review 		Cure rate
with oral ofloxacin
with parenteral cefoxitin plus oral doxycycline
Absolute results not reported
RR 0.97
95% CI 0.88 to 1.07 		Not significant
Open in a new tab

No data from the following reference on this outcome.

Symptom severity

Oral antibiotics compared with parenteral antibiotics Oral antibiotics (given as an outpatient treatment) and parenteral antibiotics (given as an inpatient treatment) may be equally effective at improving tenderness, chronic pelvic pain, and endometriosis in women with mild to moderate PID (low-quality evidence).

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Symptom severity
831 women with mild to moderate PID
In review 		Tender on exam 30 days
69/335 (21%) with single intramuscular dose of cefoxitin plus oral probenecid followed by oral doxycycline (outpatient)
63/324 (18%) with iv cefoxitin plus iv doxycycline followed by oral doxycycline (hospital admission for parenteral antibiotics; inpatient)
P = 0.50 		Not significant

RCT		 831 women with mild to moderate PID
In review 		Endometritis (on biopsy) 30 days
102/222 (46%) with single intramuscular dose of cefoxitin plus oral probenecid followed by oral doxycycline (outpatient)
85/226 (38%) with iv cefoxitin plus iv doxycycline followed by oral doxycycline (hospital admission for parenteral antibiotics; inpatient)
P = 0.09 		Not significant

RCT		 831 women with mild to moderate PID
In review 		Tubo-ovarian abscess 30 days
4/410 (0.9%) with single intramuscular dose of cefoxitin plus oral probenecid followed by oral doxycycline (outpatient)
12/398 (0.7%) with iv cefoxitin plus iv doxycycline followed by oral doxycycline (hospital admission for parenteral antibiotics; inpatient)
Significance not assessed

RCT		 831 women with mild to moderate PID
In review 		Phlebitis 30 days
0/410 (0%) with single intramuscular dose of cefoxitin plus oral probenecid followed by oral doxycycline (outpatient)
14/398 (3%) with iv cefoxitin plus iv doxycycline followed by oral doxycycline (hospital admission for parenteral antibiotics; inpatient)
Significance not assessed

RCT		 831 women with mild to moderate PID
In review 		Chronic pelvic pain 35 months
128/380 (34%) with single intramuscular dose of cefoxitin plus oral probenecid followed by oral doxycycline (outpatient)
110/369 (30%) with iv cefoxitin plus iv doxycycline followed by oral doxycycline (hospital admission for parenteral antibiotics; inpatient)
OR 1.24
95% CI 0.87 to 1.77 		Not significant
Open in a new tab

No data from the following reference on this outcome.

Rate of ectopic pregnancy

Oral antibiotics compared with parenteral antibiotics Oral antibiotics (given as an outpatient treatment) and parenteral antibiotics (given as an inpatient treatment) are equally effective at reducing rate of ectopic pregnancy in women with mild to moderate PID (low-quality evidence).

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Rate of ectopic pregnancy

RCT		 831 women with mild to moderate PID
In review 		Ectopic pregnancy 35 months
4/410 (1%) with single intramuscular dose of cefoxitin plus oral probenecid followed by oral doxycycline (outpatient)
1/398 (0.3%) with iv cefoxitin plus iv doxycycline followed by oral doxycycline (hospital admission for parenteral antibiotics; inpatient)
OR 3.66
95% CI 0.40 to 33.12 		Not significant
Open in a new tab

No data from the following reference on this outcome.

Fertility

Oral antibiotics compared with parenteral antibiotics Oral antibiotics (given as an outpatient treatment) and parenteral antibiotics (given as an inpatient treatment) may be equally effective at improving pregnancy or reducing infertility at 35 months in women with mild to moderate PID (low-quality evidence).

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Pregnancy

RCT		 831 women with mild to moderate PID
In review 		Pregnancy 35 months
174/410 (42%) with single intramuscular dose of cefoxitin plus oral probenecid followed by oral doxycycline (outpatient)
166/398 (42%) with iv cefoxitin plus iv doxycycline followed by oral doxycycline (hospital admission for parenteral antibiotics; inpatient)
Significance not assessed
Infertility

RCT		 831 women with mild to moderate PID
In review 		Infertility 35 months
71/385 (18.4%) with single intramuscular dose of cefoxitin plus oral probenecid followed by oral doxycycline (outpatient)
67/347 (17.9%) with iv cefoxitin plus iv doxycycline followed by oral doxycycline (hospital admission for parenteral antibiotics; inpatient)
OR 1.32
95% CI 0.86 to 2.04 		Not significant
Open in a new tab

No data from the following reference on this outcome.

Recurrence

Oral antibiotics compared with parenteral antibiotics Oral antibiotics (given as an outpatient treatment) and parenteral antibiotics (given as an inpatient treatment) may be equally effective at reducing recurrence of PID at 35 months (low-quality evidence).

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Recurrence

RCT		 831 women with mild to moderate PID
In review 		Recurrent PID 35 months
51/410 (12%) with single intramuscular dose of cefoxitin plus oral probenecid followed by oral doxycycline (outpatient)
66/398 (17%) with iv cefoxitin plus iv doxycycline followed by oral doxycycline (hospital admission for parenteral antibiotics; inpatient)
OR 0.69
95% CI 0.43 to 1.09 		Not significant
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No data from the following reference on this outcome.

Rate of transmission to others

No data from the following reference on this outcome.

Quality of life

No data from the following reference on this outcome.

Adverse effects

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Adverse effects

RCT		 249 women with uncomplicated pelvic inflammatory disease
In review 		Adverse effects
7% with oral ofloxacin
15% with parenteral cefoxitin plus oral doxycycline
Absolute numbers not reported
P <0.2 		Not significant

RCT		 72 women with uncomplicated acute salpingitis
In review 		Adverse effects
16% with oral ofloxacin
26% with parenteral cefoxitin plus oral doxycycline
Absolute numbers not reported
Significance not assessed

RCT		 831 women with mild to moderate PID
In review 		Adverse drug reaction
7/410 (1.7%) with single intramuscular dose of cefoxitin plus oral probenecid followed by oral doxycycline (outpatient)
6/398 (1.5%) with admission for parenteral antibiotics (inpatient)
Significance not assessed
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Further information on studies

None.

Comment

None.

Substantive changes

No new evidence

BMJ Clin Evid. 2008 Mar 10;2008:1606.

Outpatient versus inpatient antibiotic treatment

Summary

Oral antibiotics may be as effective as parenteral antibiotics in reducing symptoms and preserving fertility, with fewer adverse effects, and outpatient treatment is as effective as inpatient treatment for uncomplicated PID. However, we don't know the optimal duration.

Benefits and harms

Outpatient versus inpatient antibiotic treatment:

See option on oral versus parenteral antibiotic treatment.

Further information on studies

None.

Comment

Clinical guide:

Parenteral treatment as an inpatient offers no advantage over outpatient treatment in women with mild to moderate pelvic inflammatory disease (defined as the absence of a tubo-ovarian abscess).

Substantive changes

No new evidence

BMJ Clin Evid. 2008 Mar 10;2008:1606.

Different durations of antibiotic treatment

Summary

Oral antibiotics may be as effective as parenteral antibiotics in reducing symptoms and preserving fertility, with fewer adverse effects, and outpatient treatment is as effective as inpatient treatment for uncomplicated PID. However, we don't know the optimal duration of treatment.

We found no direct information about optimal durations of antibiotic treatment in women with PID. A 14-day treatment course is currently recommended.

Benefits and harms

Different durations of antibiotics versus each other:

We identified two systematic reviews that assessed the effects of different antibiotic regimens in the treatment of PID. Neither review assessed the effect of duration of treatment on clinical outcomes, although the most common treatment period was 14 days.

Adverse effects

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Adverse effects

Systematic review		 Number of people not reported Adverse effects 2 weeks
with metronidazole plus doxycycline
with
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No data from the following reference on this outcome.

Further information on studies

None.

Comment

Clinical guide:

A 14-day treatment course is recommended for pelvic inflammatory disease based on the current evidence.

Substantive changes

No new evidence

BMJ Clin Evid. 2008 Mar 10;2008:1606.

Routine antibiotic prophylaxis before IUD insertion in women at high risk

Summary

We found no direct information from RCTs about antibiotic prophylaxis before IUD insertion in women at high risk of pelvic inflammatory disease.

Risks of PID may be increased after instrumentation of the cervix, and testing for infection before such procedures is advisable, but we don't know whether prophylactic antibiotics before IUD insertion reduce these risks.

Benefits and harms

Antibiotic prophylaxis before IUD insertion in women at high risk:

We found no RCTs on the effects of routine antibiotic prophylaxis in women at high risk of pelvic inflammatory disease.

Further information on studies

None.

Comment

Nausea and vomiting has been reported with 17% to 28% of healthy volunteers on doxycycline, depending on the formulation given. See harms of antibiotics (for symptoms and microbiological clearance in women with confirmed pelvic inflammatory disease).

Substantive changes

No new evidence

BMJ Clin Evid. 2008 Mar 10;2008:1606.

Routine antibiotic prophylaxis before IUD insertion in women at low risk

Summary

Risks of PID may be increased after instrumentation of the cervix, and testing for infection before such procedures is advisable, but prophylactic antibiotics in women at low risk of PID seem no more effective than placebo at reducing rate of PID.

Benefits and harms

Antibiotic prophylaxis before IUD insertion versus no antibiotic prophylaxis (in women at low risk):

We found one systematic review (search date 2002, 4 RCTs, 3598 women requesting IUD insertion).

Rate of PID

Antibiotic prophylaxis compared with placebo Antibiotic prophylaxis before IUD insertion is no more effective than placebo at reducing the incidence of pelvic inflammatory disease in women at low risk of pelvic inflammatory disease (moderate-quality evidence).

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Rate of PID

Systematic review		 3598 women requesting IUD insertion
4 RCTs in this analysis		 Incidence of PID
with single dose of doxycycline 200 mg (1 hour before IUD insertion)
with placebo (1 hour before IUD insertion)
Absolute results not reported
OR 0.89
95% CI 0.53 to 1.51
The wide confidence interval suggests that the study may have lacked power to detect a clinically important difference 		Not significant
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No data from the following reference on this outcome.

Further information on studies

None.

Comment

Nausea and vomiting has been reported with 17% to 28% of healthy volunteers on doxycycline, depending on the formulation given. See harms of antibiotics (for symptoms and microbiological clearance in women with confirmed pelvic inflammatory disease).

Clinical guide:

In the populations included in the systematic review, the risk of pelvic inflammatory disease (PID) after IUD insertion was low. The occurrence of PID in this group usually reflects the introduction of infection into the uterus during IUD insertion, and will therefore vary with the prevalence of STDs in the population. A further systematic review also found that the absolute risk of PID was low even when gonorrhoea or chlamydia was present at the time of IUD insertion (0–5% for those with an STD compared with 0–2% in those without an STD).

Substantive changes

No new evidence

Articles from BMJ Clinical Evidence are provided here courtesy of BMJ Publishing Group

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