Amoxicillin prescribing information

However, although all patients with anaerobic bacteria cultured at study admission were considered to be clinically cured at follow-up in one of these studies [ 24], follow-up anaerobic cultures were not reported, and therefore, microbiological cure of anaerobes cannot be determined.

Because the lack of anaerobic coverage with ofloxacin is a concern, emphasized by the high rate of treatment failure among patients with nongonococcal, nonchlamydial PID [ 16], the Centers for Disease Control and Prevention suggests the optional addition of metronidazole [ 13]. Alternatively, a randomized clinical trial of 131 women with laparoscopically confirmed PID investigated the regimen of another fluoroquinolone, ciprofloxacin, plus clindamycin [ 17]. In this study, clindamycin-ciprofloxacin was found to be as effective as ceftriaxone plus doxycycline for amoxicillin 300 mg the clinical cure of PID (97% vs. trachomatis eradication (100% in both groups) [ 17].

gonorrhoeae was less prevalent; it was found in only 2 women who were treated with clindamycin plus ciprofloxacin, and 1 of these women achieved microbiological cure (a cure rate of 50%).

Although aerobic and anaerobic isolates were frequently identified before treatment, no comparisons of microbiological cure for these pathogens were presented. In the most recent fluoroquinolone randomized clinical trial by Ross et al.

[ 18], moxifloxacin was found to have high rates of clinical resolution (90%) and microbiological cure. genitalium, Escherichia coli , and other gram-negative anaerobes.

trachomatis was lower (89%), it was slightly higher than that of the comparator regimen (86%) [ 18]. gonorrhoeae was much higher (100%, compared with 82%) and the rate of drug-related adverse events was lower (23%, compared with 31%) among women treated with moxifloxacin.

Also of interest because of its association with enhanced compliance, single-dose or short-duration azithromycin in the treatment of PID has been examined in a handful of studies.

Not surprisingly, compliance with single-dose azithromycin therapy has been reported to be 100% [ 25].

In a randomized clinical trial from India of 165 women with clinically suspected PID, a kit containing 1 tablet of fluconazole (150 mg), 1 tablet of azithromycin (1 g), and 2 tablets of secnidazole (2 g) was associated with a PID clinical cure rate of 93%, which is similar to that found among a group treated with ciprofloxacin plus tinidazole for 7 days (clinical cure rate, 96%) and better than that found among women treated with doxycycline plus metronidazole for 1 week (clinical cure rate, 91%) [ 19]. However, although this trial showed high rates of clinical cure, data on microbiological cure were not presented.

In a randomized clinical trial in the United Kingdom that compared azithromycin monotherapy, azithromycin plus metronidazole, and standard 21-day regimens of metronidazole-doxycycline-cefoxitin-probenecid or doxycycline-amoxicillin-clavulanate among 300 patients with PID, azithromycin was found to have a high rate of clinical success, similar to that of other regimens (97% for azithromycin monotherapy, compared with 96% for azithromycin-metronidazole and 95% for a comparator regimen) [ 20].

Moreover, azithromycin provided excellent rates of eradication of C. Complicating the interpretation of this study, however, was the combining of 2 different trials in the analyses. In 1 trial, 500 mg of azithromycin was administered intravenously on day 1, followed by 250 mg of oral azithromycin for 6 days. In the other trial, the intravenous protocol was conducted for 2 days, followed by oral azithromycin therapy for 5 days.

The comparator regimens in each trial differed as well. Therefore, the optimal azithromycin regimen cannot be determined. Furthermore, the dropout rate at the final follow-up visit was extremely high (78%), and this reduces the validity and generalizability of the microbiological cure evaluation. A few studies have further examined the outpatient combination regimen of doxycycline and metronidazole.

In a randomized clinical trial of 40 patients with laparoscopically confirmed salpingitis, combined doxycycline-metronidazole treatment exhibited a low clinical cure rate of 35%, with a 50% clinical improvement rate [ 21].

The low efficacy of this regimen was replicated in an observational study in the United Kingdom involving 135 women with PID, in which only 55% experienced a clinical cure 2 or 4 weeks after treatment [ 26]. The addition of ceftriaxone to this regimen resulted in a higher but still suboptimal cure rate of 72% [ 26].

Because combined doxycycline-metronidazole provides poor coverage against N.

gonorrhoeae and was also associated with the lowest pooled clinical and microbiological cure rates in the meta-analysis conducted by Walker et al. [ 14], this is not considered to be an optimal regimen for treatment of PID.

Most randomized clinical trials of monotherapy for PID have been conducted among women with mild to moderate PID who were treated as outpatients. In a study of 84 women hospitalized because of PID, meropenem, which has demonstrated in vitro activity against a broad spectrum of gram-negative and gram-positive aerobic and anaerobic bacteria, was found to be associated with high rates of clinical response and

microbiological

Among the recent trials of treatment for PID, regimens including ofloxacin, moxifloxacin, azithromycin, and clindamycin-ciprofloxacin all yielded high rates of clinical cure and eradication of N. trachomatis , although microbiological cure data among women with PID due to anaerobes are limited.

This is attributable, in part, to the complexity of studying PID due to anaerobes, because the organisms may be present as commensal bacteria in the lower genital tract, and transcervical sampling of the endometrium may result in contamination of endometrial biopsy specimens by vaginal or cervical microorganisms.

However, we have previously demonstrated that contamination likely does not account for the relationships between bacterial vaginosis–associated microorganisms and acute endometritis.

In the PID Evaluation and Clinical Health (PEACH) study, we have shown that anaerobic gram-negative bacteria are associated with acute endometritis independent of bacterial vaginosis [ 9].

Furthermore, anaerobic gram-negative rods and anaerobic gram-positive cocci—but not other organisms frequent among women with bacterial vaginosis (e.g., Gardnerella vaginalis and M. hominis )—are associated with acute endometritis [ 9]. Another barrier to the study of microbiological cure of PID is the lack of 100% correlation between the microbiological makeup of the endometrium and fallopian tube

and

Despite the challenges facing the study of PID due to anaerobic organisms as a result of the fact that only one-third to one-half of PID cases are attributed to N.

trachomatis and the fact that bacterial vaginosis, anaerobic gram-negative rods, and mycoplasmal bacteria have been identified among women with PID [ 9, 10, 12, 27, 28], the microbiological efficacy of treatment regimens for both chlamydial and/or gonococcal and nonchlamydial and/or nongonococcal PID should be determined.

Unfortunately, previous trials of metronidazole showed it to have limited efficacy, perhaps because poor tolerability limits adherence. Indeed, the highest rates of adverse effects and study discontinuation in the randomized clinical trials reviewed herein occurred in women who were assigned to comparator regimens containing metronidazole [ 18–20].

This fact underscores the need for research on agents for the treatment of PID that are bactericidal for anaerobes. Regimens with shorter duration and monotherapy regimens are promising and may increase compliance and decrease sequelae. However, there is currently limited evidence for the recommendation of alternative therapies for the treatment of anaerobic PID.

Although azithromycin provides coverage against a range of anaerobic and aerobic pathogens (including black-pigmented gram-negative rods) [ 20, 29], fluoroquinolones, including ofloxacin, have generally been found to have limited activity against anaerobes [ 30, 31]. In a recent trial of moxifloxacin versus ofloxacin plus metronidazole, moxifloxacin was found to be as clinically efficacious as ofloxacin plus metronidazole and to exhibit similar cure rates for C. trachomatis and Mycoplasma and better cure rates for N.

However, women treated with moxifloxacin experienced a worse cure rate for gram-positive anaerobes [ 18].

Alternatively, a study has amoxicillin & clavulanic acid shown azithromycin to be effective for the treatment of anaerobic PID [ 20].

Clinical cure rates and eradication of anaerobes are similar among women whose PID is treated with azithromycin alone and women treated with combination azithromycin-metronidazole (clinical cure rate, 97% vs.

This initial study is promising, and further work may support the use of azithromycin monotherapy for the treatment of anaerobic PID. However, neither azithromycin nor quinolones are optimal for the treatment of gonococcal PID, because increasing drug resistance is being reported [ 32–36].

Treatment efficacy in the studies reviewed was restricted to short-term clinical and microbiological cure.

There are limited data on the efficacy of any PID treatment regimen in the prevention of adverse reproductive sequelae.

From the PEACH study, we have previously reported that, among women with clinically suspected mild to moderate PID treated with the standard antibiotic regimen of doxycycline and cefoxitin, endometritis and upper genital tract gonococcal and chlamydial infection were not associated with reproductive morbidity [ 37].

One interpretation is that these antibiotics that are used to treat modern-day mild to moderate chlamydial and gonococcal PID limited to the uterus are so effective that reproductive morbidity is not elevated among women with treated endometritis. However, despite the high rates of clinical cure and eradication of N.

trachomatis observed in the PEACH study at 30 days after

treatment

This suggests a need to discover and provide coverage against all possible damaging PID pathogens

and

trachomatis identified, 22% for women with anaerobic bacteria identified, 27% for women with U.

hominis identified; chronic pelvic pain rates were 27% for women with N. trachomatis identified, 33% for women with anaerobic bacteria identified, 41% for women with U. [ 40] of 50 women with laparoscopically confirmed salpingitis, 54% of women with nongonococcal infections had future adverse reproductive outcomes, compared with none of the women with gonococcal infections. Collectively, the PEACH study [ 37] and the study by Brunham et al. [ 40] suggest that, although these regimens may have high short-term clinical and microbiological cure rates, the standard antibiotic regimens of doxycycline-cefoxitin [ 37], doxycycline-clindamycin [ 40], and doxycycline-metronidazole [ 40] may not be optimal for the prevention of adverse sequelae among women with nongonococcal PID.