Treatment for pelvic inflammatory disease

Review question

We assessed the effectiveness and safety of different treatments for pelvic inflammatory disease (PID) that are recommended for consideration by current clinical guidelines for treatment of PID (the 2015 US Centers for Disease Control and Prevention guidelines for treatment of PID).

Background

PID is an infection of the upper part of the woman's reproductive system (womb, fallopian tubes (tube connecting the womb and ovary that the egg travels along), ovaries (which make eggs), and inside of the pelvis). It is a common condition affecting women of childbearing age. Symptoms of PID vary, ranging from no symptoms to severe symptoms. If effective treatment is not started promptly, the consequences of the condition can be infertility (unable to have children), pregnancies outside of the womb, and chronic pelvic pain (pain in the lower tummy). There is a wide range of treatment options, the choice of which is based on severity of symptoms, experience of the doctor, national/international guidelines, and rate of side effects. We wanted to learn if there is a better antibiotic (used to treat bacterial infections) therapy with higher rates of cure and lower side effects to treat PID.

Trial characteristics

We searched the available literature up to 11 July 2016 and included 37 studies with 6348 women with an average of 14 days of treatment and follow-up (monitoring after treatment). These trials included women of childbearing age with mild to severe PID. Trials mostly used a combination of antibiotics with different administration routes: intravenous (into a blood vessel), intramuscular (into the muscle), and oral (as a tablet). In mild-moderate cases, intramuscular and oral treatments were prescribed, and in moderate-severe cases, treatments were usually started in hospital and were completed at home.

Key results

We found no conclusive evidence that one treatment was safer or more effective than any other for the cure of PID, and there was no clear evidence for the use of nitroimidazoles (a type of antibiotic; metronidazole) compared to use of other antibiotics. Moderate-quality evidence from a single study at low risk of bias suggested that a macrolide (a type of antibiotic; azithromycin) may be more effective than a tetracycline (a type of antibiotic; doxycycline) for curing mild-moderate PID.

Quality of evidence

The quality of the evidence ranged from very low to high, the main problems being serious risk of bias (poor reporting of study methods; doctors and women may have known which medicine was given), and results differed across studies.

Authors' conclusions: 

We found no conclusive evidence that one regimen of antibiotics was safer or more effective than any other for the cure of PID, and there was no clear evidence for the use of nitroimidazoles (metronidazole) compared to use of other drugs with activity over anaerobes. Moderate-quality evidence from a single study at low risk of bias suggested that a macrolide (azithromycin) may be more effective than a tetracycline (doxycycline) for curing mild-moderate PID. Our review considered only the drugs that are currently used and mentioned by the CDC.

Read the full abstract...
Background: 

Pelvic inflammatory disease (PID) is an infection that affects 4% to 12% of young women, and is one of the most common causes of morbidity in this age group. The main intervention for acute PID is the use of broad-spectrum antibiotics which cover Chlamydia trachomatis, Neisseria gonorrhoeae, and anaerobic bacteria, administered intravenously, intramuscularly, or orally. In this review, we assessed the optimal treatment regimen for PID.

Objectives: 

To assess the effectiveness and safety of antibiotic regimens used to treat pelvic inflammatory disease.

Search strategy: 

We searched the Cochrane Sexually Transmitted Infections Review Group's Specialized Register, which included randomized controlled trials (RCTs) from 1944 to 2016, located through electronic searching and handsearching; the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid platform (1991 to July 2016); MEDLINE (1946 to July 2016); Embase (1947 to July 2016); LILACS, iAHx interface (1982 to July 2016); World Health Organization International Clinical Trials Registry Platform (July 2016); Web of Science (2001 to July 2016); OpenGrey (1990, 1992, 1995, 1996, and 1997); and abstracts in selected publications.

Selection criteria: 

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

Data collection and analysis: 

At least two review authors independently selected trials for inclusion, extracted data, and assessed risk of bias. We contacted investigators to obtain missing information. We resolved disagreements by consensus or by consulting a fourth review author if necessary. We assessed the quality of the evidence using GRADE criteria, classifying it as high, moderate, low, or very low. We calculated Mantel-Haenszel risk ratios (RR), using either random-effects or fixed-effect models and number needed to treat for an additional beneficial outcome or for an additional harmful outcome, with their 95% confidence interval (CI), to measure the effect of the treatments. We conducted sensitivity analyses limited to studies at low risk of bias, for comparisons where such studies were available.

Main results: 

We included 37 RCTs (6348 women). The quality of the evidence ranged from very low to high, the main limitations being serious risk of bias (due to poor reporting of study methods and lack of blinding), serious inconsistency, and serious imprecision.

Azithromycin versus doxycycline

There was no clear evidence of a difference between the two drugs in rates of cure for mild-moderate PID (RR 1.18, 95% CI 0.89 to 1.55, I2 = 72%, 2 RCTs, 243 women, very low-quality evidence), severe PID (RR 1.00, 95% CI 0.96 to 1.05, 1 RCT, 309 women, low-quality evidence), or adverse effects leading to discontinuation of treatment (RR 0.71, 95% CI 0.38 to 1.34, 3 RCTs, 552 women, I2 = 0%, low-quality evidence). In a sensitivity analysis limited to a single study at low risk of bias, azithromycin was superior to doxycycline in achieving cure in mild-moderate PID (RR 1.35, 95% CI 1.10 to 1.67, 133 women, moderate-quality evidence).

Quinolone versus cephalosporin

There was no clear evidence of a difference between the two drugs in rates of cure for mild-moderate PID (RR 1.04, 95% CI 0.98 to 1.10, 3 RCTs, 459 women, I2 = 5%, low-quality evidence), severe PID (RR 1.06, 95% CI 0.91 to 1.23, 2 RCTs, 313 women, I2 = 7%, low-quality evidence), or adverse effects leading to discontinuation of treatment (RR 2.24, 95% CI 0.52 to 9.72, 5 RCTs, 772 women, I2 = 0%, very low-quality evidence).

Nitroimidazole versus no use of nitroimidazole

There was no conclusive evidence of a difference between the nitroimidazoles (metronidazole) group and the group receiving other drugs with activity over anaerobes (e.g. amoxicillin-clavulanate) in rates of cure for mild-moderate PID (RR 1.01, 95% CI 0.93 to 1.10, 5 RCTs, 2427 women, I2 = 60%, moderate-quality evidence), severe PID (RR 0.96, 95% CI 0.92 to 1.01, 11 RCTs, 1383 women, I2 = 0%, moderate-quality evidence), or adverse effects leading to discontinuation of treatment (RR 1.00, 95% CI 0.63 to 1.59; participants = 3788; studies = 16; I2 = 0% , low-quality evidence). In a sensitivity analysis limited to studies at low risk of bias, findings did not differ substantially from the main analysis (RR 1.06, 95% CI 0.98 to 1.15, 2 RCTs, 1201 women, I2 = 32%, high-quality evidence).

Clindamycin plus aminoglycoside versus quinolone

There was no evidence of a difference between the two groups in rates of cure for mild-moderate PID (RR 0.88, 95% CI 0.69 to 1.13, 1 RCT, 25 women, very low-quality evidence), severe PID (RR 1.02, 95% CI 0.87 to 1.19, 2 studies, 151 women, I2 = 0%, low-quality evidence), or adverse effects leading to discontinuation of treatment (RR 0.21, 95% CI 0.02 to 1.72, 3 RCTs, 163 women, very low-quality evidence).

Clindamycin plus aminoglycoside versus cephalosporin

There was no clear evidence of a difference between the two groups in rates of cure for mild-moderate PID (RR 1.02, 95% CI 0.95 to 1.09, 2 RCTs, 150 women, I2 = 0%, low-quality evidence), severe PID (RR 1.00, 95% CI 0.95 to 1.06, 10 RCTs, 959 women, I2 = 21%, moderate-quality evidence), or adverse effects leading to discontinuation of treatment (RR 0.78, 95% CI 0.18 to 3.42, 10 RCTs, 1172 women, I2 = 0%, very low-quality evidence).

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