Pelvic inflammatory disease (PID) involves a spectra of upper genital tract inflammations, including endometritis, salpingitis, parametritis, oophoritis, tubo-ovarian abscess, and/or pelvic peritonitis [1, 2]. PID affects sexually active young women, often caused by STIs, with early treatment crucial to prevent severe complications [3–5]. PID most commonly occurs among women with sexually transmitted diseases; women with PID account for 1–2% of the female sexually mature population. Moreover, there are severe regional differences in terms of the incidence worldwide [6]. PID is usually caused by infections ascending from the vagina and endocervix. Women of reproductive age and sexually active adolescents are at high risk of PID. When untreated or incompletely treated, PID can have serious clinical consequences, including infertility, ectopic pregnancy, and chronic pelvic pain. Because of its high incidence and severe sequelae, PID is an important public health concern. However, PID cannot reliably be diagnosed based on clinical signs and symptoms; therefore, the exact incidence of it remains unknown. Price et al. reported that 1.1% of women aged 16–44 years who visit primary care physicians in England are diagnosed with PID [7].
The accuracy of the clinical diagnosis of PID is unsatisfactory [8]. However, the diagnosis of PID remains dependent on the lowest diagnostic standard [1]. The following features and symptoms occurring simultaneously should be indicative of PID. The clinical features of PID include lower abdominal pain, deep dyspareunia, abnormal bleeding (intermenstrual bleeding, postcoital bleeding, and menorrhagia) secondary to cervicitis and endometritis, and abnormal vaginal or cervical discharge; the physical signs of PID include lower abdominal tenderness, adnexal tenderness, cervical motion tenderness, and fever (> 38°C). A variety of causative agents for PID have been identified, including sexually transmitted organisms, such as Neisseria gonorrhea and Chlamydia trachomatis, as well as lower genital tract endogenous anaerobes [9]. Additionally, PID may be caused by Mycoplasma genitalium and Ureaplasma urealyticum in some cases [10].
The objectives of antimicrobial therapy for patients with PID include antimicrobial therapy, controlling the symptoms and preventing the late sequelae of the disease [11]. Because of the diversity of the microflora involved in PID, broad-spectrum antibiotic and combination antibiotics are recommended. Guidelines for PID management have been developed in the United States as well as in Europe [12, 13]. The regimens recommended for improving bacteria coverage include metronidazole, a member of the nitroimidazole drug class [14, 15]. The side effects of metronidazole include a metallic taste, nausea, transient neutropenia, and peripheral neuropathy. However, after several decades of worldwide use of metronidazole, antimicrobial resistance for it has emerged [16–18]. One study demonstrated that the resistance rate of Bacteroides fragilis to metronidazole was 38.46% [19]. Accordingly, much effort has been expended to explore structurally different drugs belonging to the nitroimidazole class that may be more effective against PID-causing bacteria.
Levornidazole is a third-generation nitroimidazole antimicrobial that is used worldwide as an alternative to metronidazole. Levornidazole is used to treat protozoan and bacterial infections. Its mechanism of action involves reactivation by reduction of the nitro group and production of toxic derivatives and radicals [20]. The recommended dose of levornidazole is 500 mg twice daily given intravenously.
Levornidazole disodium phosphate, a national class I antimicrobial, is a novel third-generation nitroimidazole antimicrobial used for the treatment of amoebiasis, trichomoniasis, and anaerobic bacterial infections. This drug exhibits greater activity and less toxicity than metronidazole [21, 22]. In cases of PID or appendicitis, 1.0 g of this antimicrobial is administered intravenously once daily. In this study, we compared the efficacy and safety of treating women with PID using intravenous levornidazole disodium phosphate once daily and intravenous levornidazole twice daily.