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BMJ Clin Evid. 2008; 2008: 1606.
Published online 2008 March 10.
PMCID: PMC2907941

Pelvic inflammatory disease

Jonathan D C Ross, MB ChB MD FRCP, Professor of Sexual Health and HIV

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).

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.

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.

Notes

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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2008; 2008: 1606.
Published online 2008 March 10.

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

2008; 2008: 1606.
Published online 2008 March 10.

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).

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)PopulationOutcome, InterventionsResults and statistical analysisEffect sizeFavours
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 sizedoxycycline 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 sizelymecycline

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

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)PopulationOutcome, InterventionsResults and statistical analysisEffect sizeFavours
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

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).

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).

2008; 2008: 1606.
Published online 2008 March 10.

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)PopulationOutcome, InterventionsResults and statistical analysisEffect sizeFavours
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

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)PopulationOutcome, InterventionsResults and statistical analysisEffect sizeFavours
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

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)PopulationOutcome, InterventionsResults and statistical analysisEffect sizeFavours
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

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)PopulationOutcome, InterventionsResults and statistical analysisEffect sizeFavours
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

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)PopulationOutcome, InterventionsResults and statistical analysisEffect sizeFavours
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

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)PopulationOutcome, InterventionsResults and statistical analysisEffect sizeFavours
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

Further information on studies

None.

Comment

None.

Substantive changes

No new evidence

2008; 2008: 1606.
Published online 2008 March 10.

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

2008; 2008: 1606.
Published online 2008 March 10.

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)PopulationOutcome, InterventionsResults and statistical analysisEffect sizeFavours
Adverse effects

Systematic review
Number of people not reported Adverse effects 2 weeks
with metronidazole plus doxycycline
with

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

2008; 2008: 1606.
Published online 2008 March 10.

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

2008; 2008: 1606.
Published online 2008 March 10.

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)PopulationOutcome, InterventionsResults and statistical analysisEffect sizeFavours
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

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


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