Treatment

Treatment of PID should produce high rates of clinical and micro­biological cure for the principal pathogens described previously, as well as prevent long-term sequelae such as infertility, ectopic preg­nancy, and chronic pelvic pain.

The first consideration is whether the woman requires inpatient or outpatient management. The indications for hospitalization in­clude pregnancy, severe illness with high fever and inability to take oral medication, tubo-ovarian abscess, inability to rule out other serious diagnoses, and lack of clinical response to oral therapy. Once started, parenteral treatment should be continued for at least 24 hours after clinical improvement. There is no evidence, however, that treating women with mild to moderate PID in the inpatient set­ting is more effective than outpatient therapy. In the PEACH study, both short-term clinical and microbiological cure and long-term reproductive outcomes were similar in both the inpatient and out­patient groups (5). Remarkably, this was despite subjects taking only an average of 70% of the prescribed doses (61).

The choice of treatment should reflect drug availability and cost, antimicrobial susceptibility, local epidemiology of specific infective organisms, and disease severity. Based on an understanding of the polymicrobial aetiology, PID should be treated with antibiotics covering a broad spectrum of pathogens.

There is debate whether to include anaerobic coverage in treat­ment regimens, which stems from the poor understanding of whether anaerobes are implicated in the pathogenesis of PID. While the prevalence of anaerobes in the upper genital tract of women with PID is variable, it is accepted that when present they can cause local tissue damage. Treatment trials have documented excellent clinical and microbiological cure rates both for regimens that offer adequate anaerobic coverage, and for regimens that do not, although few trials have documented anaerobic microbiological cure data specifically.

While it is recognized that severe disease is usually polymicrobial, and often includes anaerobes, the role of anaerobes in mild to moderate disease is less clear. Many studies have shown that BV- associated organisms are more frequently found in women with PID. In the PEACH study, for example, 53.5% of women had con­comitant BV, and women with acute endometritis on endometrial biopsy were commonly infected with BV-associated microorgan­isms in the upper genital tract (G. vaginalis 30.9%, anaerobic Gram­negative rods 31.7%, and anaerobic Gram-positive cocci 22%) (24, 25). The outpatient regimen in the PEACH study, however, had only a single dose of a second-generation cephalosporin (cefoxitin 2 g intramuscularly, plus probenecid 1 g orally) which may not have been sufficient to clear upper genital tract anaerobic infection. Although short- and long-term outcomes were similar in the in­patient and outpatient treatment arms, there were a large propor­tion of women in both arms with persistent endometritis at 30 days (45.9% outpatient, 37.6% inpatient; P = 0.09) (5). If anaerobes can persist and cause ongoing inflammation following treatment with suboptimal antibiotic regimens, including sufficient anaerobic cover would seem to be essential.

Current European and United Kingdom guidelines include agents which cover N. gonorrhoeae, C. trachomatis, and anaerobic infec­tion (40, 59) (Tables 43.2 and 43.3). As a result of the emergence of quinolone-resistant N. gonorrhoeae, regimens that include a quinolone

Table 43.2 Oral treatment regimens for pelvic inflammatory disease

BD, twice daily

^a Ofloxacin and moxifloxacin should be avoided in patients who are at high risk of gonococcal PID because of increasing quinolone resistance in the United Kingdom (e.g.

^b May be discontinued in patients with mild to moderate PID who are unable to tolerate it.

agent are either no longer routinely recommended (2), or only re­commended when there is a low probability of N. gonorrhoeae being the causative agent. Quinolones should be avoided in patients where the partner has gonorrhoea, in clinically severe disease, or following sexual contact abroad. Quinolones should also be avoided as first-line empirical treatment for PID in areas where more than 5% of PID is caused by quinolone-resistant N. gonorrhoeae (40, 59). In 2018 the European Medicines Agency highlighted the potential for disabling and permanent side effects following the use of quinolone antibiotics (62), with the subsequent downgrading of ofloxacin to second-line therapy in UK guidelines (59). For outpatient regimens there are dif­ferences in the recommended dosage of intramuscular ceftriaxone between the European and CDC guidelines. Ihc higher dose of intra­muscular ceftriaxone is recommended in the European guidelines to reduce the risk of resistance developing in N. gonorrhoeae.

The current recommended therapies in most national guidelines specify the use of antibiotics with low efficacy against M. genitalium. It has been well documented that clearance of this organism after doxy­cycline is poor and older fluoroquinolones (ciprofloxacin, ofloxacin) have limited activity against M. genitalium. Among women with a positive baseline M. genitalium test in the PEACH study, 41% tested positive again at 30 days following intramuscular cefoxitin and oral doxycycline (63). Women with mycoplasma identified in the endomet­rium were 4.5 times more likely to experience short-term treatment failure.

In conclusion, it remains a challenge to provide antibiotic coverage for gonococcal, chlamydial, mycoplasma, and anaerobic infection. Presumptive therapy with moxifloxacin in persistent cases, unre­sponsive to standard regimens, to cover M. genitalium may be war­ranted. While potentially more effective, combination regimens may be associated with increased drug cost and more adverse effects, when compared to currently recommended treatments.

Table 43.3 Parenteral treatment regimens for pelvic inflammatory disease

BD, twice daily; QDS, four times a day; TDS, three times a day, ^a Gentamicin levels need to be monitored if this regimen is used.