Is Cefoxitin a Carbapenem Sparing Agent in the Management of Urinary Tract Infections Caused by ESBL Producing Enterobacterales?

Background: Cefoxitin has shown in vitro activity against Extended-Spectrum β-Lactamase (ESBL) producing Enterobacterales. Outcome data regarding cefoxitin as a carbapenem sparing agent in the management of urinary tract infections (UTI) are scarce. We sought to evaluate the clinical and microbiologic efficacy of cefoxitin as compared to ertapenem. Methods: A retrospective observational study was conducted at our quaternary care institution between May 2015 and March 2019. We identified all patients who received cefoxitin for the treatment of UTI during the study period and used Charlson Comorbidity Index to select a matching cohort from patients who received ertapenem. Primary end points were clinical and microbiological cure. Results: Thirty patients who received cefoxitin were matched with 55 patients who received ertapenem. Clinical cure was marginally in favor of ertapenem: 83.2% in cefoxitin group versus 96.8% in ertapenem group ( P = .042). However, 90-day recurrence was in favor of cefoxitin: 13.5% in cefoxitin group versus 34.8% in ertapenem group ( P = .045). Microbiologic cure was not significant between the 2 groups with 88.6% success in cefoxitin versus 100% in ertapenem. Additionally, the group difference on 30-day recurrence or relapse rates and the 90-day mortality rate were not clinically significant. Conclusion: Cefoxitin achieved similar microbiologic cure rate when compared to ertapenem for the treatment of UTI caused by ESBL-producing Enterobacterales. No significant differences were found in 30-day recurrence/relapse or mortality rates. Larger randomized controlled trials are required to identify the clinical sittings in which cefoxitin could be used as a carbapenem-sparing agent in the treatment of UTI.

Evaluation of treatment with two weeks of doxycycline on macrolide-resistant strains of Mycoplasma genitalium: a retrospective observational study

Background Increasing macrolide resistance makes treatment of Mycoplasma genitalium infections challenging. The second-line treatment is moxifloxacin, an antibiotic drug best avoided due to the potential of severe side effects and interactions. This study evaluates the effects of treatment with doxycycline 100 mg twice daily for 2 weeks as an alternative to moxifloxacin. Methods This retrospective observational study examined the medical records of patients testing positive for macrolide resistant Mycoplasma genitalium from January 1st, 2016 to September 1st, 2019 in Trondheim, Norway. Information regarding symptoms as well as clinical and microbiological cure was collected. Results 263 infections from 259 patients (161 females/98 males) were examined. 155 (58.9%) had a negative test of cure following treatment. 34.7% of symptomatic patients not achieving microbiological cure experienced symptom relief or clearance. There was no statistical difference between bacterial loads in symptomatic versus asymptomatic patients. The mean difference was 1.6 × 105 copies/ml (95% CI − 1.4 × 105–4.8 × 105, p = 0.30) for women and 1.4 × 106 copies/ml (95% CI -4.0 × 105–3.2 × 106, p = 0.12) for men. Conclusions The cure rate of doxycycline in this study is higher than previously reported. This adds support to doxycycline’s role in treatment before initiating treatment with less favorable drugs such as moxifloxacin.

Mixed sexually transmitted infections in infertile couples: empirical treatment and influence on semen quality

Background: Trichomonas vaginalis (TV), Mycoplasma genitalium (MG) and Ureaplasma urealyticum (UU) are common sexually transmitted infections (STIs) that are diagnosed in infertile couples (cps). In cases with their simultaneous presence in a patient (mixed STI, MSTIs), treatment is complicated by the different sensitivity of microorganisms to antibacterial drugs. Moreover, in cases of complicated infections, the empirical treatment should be started before obtaining the results of drug susceptibilities. Objective: The objective of the current study is to find the effective and well-tolerated combination of drugs for the empirical antibacterial treatment of mixed STIs presented by TV, MG and UU in infertile couples. We also aimed to establish the influence of mixed STIs on semen quality. Method: Our prospective study included 154 infertile couples (308 patients) with confirmed symptomatic MSTIs in one of the couples caused by the simultaneous presence of TV, MG and UU. All couples were randomized on three groups for empirical treatment: Group 1 (n=49 cps, 98 pts) who were treated by initial prescribing of anti-trichomoniasis drug Secnidazole, 2.0 g po followed by Azythromycin 500 mg on day 1 continuing by 250 mg on days 2-7; Group 2 (n=52 cps, 104 pts: Secnidazole, 2.0 g po followed by Josamycin 1000 mg bid for 12 days); Group 3 (n=53 cps, 106 pts: Secnidazole, 2.0 g po followed by Moxifloxacin 400 mg once daily for 12 days). The endpoints were clinical and microbiological cure rates as well as the frequency of side-effects in analyzed groups. We determined the basic parameters of the spermogram and Deoxyribonucleic acid (DNA) fragmentation levels in 59 patients with MSTIs before and at the 3rd, 6th and 9th month after pathogens eradication comparing them with results in 63 healthy sperm donors. Result: After the treatment, clinical cure rates in analyzed groups were 82.6% (Group 1) vs 96.1% (Group 2) vs 92.3% (Group 3). Microbiological cure rates (UU+MG) were 73.9 % vs 97.1 % vs 84.5% correspondingly (p<0.05). TV microbiological cure rates were 97.8% vs 98.0% vs 96.1% (p>0.05). Side-effects were registered in 28.6% vs 12.5% vs 18.9% cases correspondingly (p<0.05). In MSTIs patients, we registered the increasing DNA fragmentation rates, leucocytes count and decreasing semen volume, motility, vitality, sperm concentration, total spermatozoa number and number of spermatozoa with normal morphology. At the 6th month after complete pathogens eradication, these parameters approached normal values. Conclusion: At the present time, the combination of Secnidazole+Josamycin can be considered the most effective and well-tolerated for the empirical treatment in patients with MSTIs presented by TV, MG and UU. Complete eradication of these MSTIs in males improves their semen parameters.

A New Therapy for Uncomplicated Vulvovaginal Candidiasis and Its Impact on Vaginal Flora

Background: An estimated 75% of women will have one episode of vulvovaginal candidiasis (VCC) during their lifetime, and 40–50% of these will experience further episodes. The high incidence of vulvovaginal candidiasis, combined with the problems of azole resistance and toxicity, highlights the necessity for new strategies for the treatment of this condition. In this context, natural compounds represent promising alternatives. Methods: We enrolled, between January 2020 and April 2021, forty women affected by uncomplicated vulvovaginal candidiasis. Women were divided into two groups. In the first group, we treated 20 women with clotrimazole daily administration for six days. In the second group, 20 women were treated with clotrimazole associated with Unilen® Microbio+, a new product containing Saccharomyces cerevisiae, melatonin, and GLA-14. Women underwent a check at days 15, 30, and 90. A clinical and cultural examination were performed to establish the effect of the treatments on vaginal flora. Results: In the group treated with Unilen® Microbio+, clinical and microbiological cure at 15 and 30 days was observed in 18 women (90%), compared with 16 women (80%) in the group treated only with clotrimazole. The efficacy of the association between clotrimazole and Unilen® Microbio+ in these uncomplicated forms was therefore not inferior to the azole treatment alone. Only four women (20%) in the Unilen® Microbio+ group presented symptomatic recurrences within the 3 months, compared with eight women (40%) in the clotrimazole-only group. Microscopic wet mount analysis at 1 and 3 months demonstrated a significant increase in lactobacillus count and a reduction in the polymorphonucleate cells in the Unilen® Microbio+ group. Conclusions: Unilen® Microbio+ supplementation was demonstrated to cure uncomplicated vulvovaginal candidiasis with clotrimazole, reducing recurrence and improving vaginal flora better than clotrimazole treatment alone.

1417. Fosfomycin Use in the Treatment of Complicated Urinary Tract Infections at a Veterans Affairs Medical Center

Background The prevalence of multidrug resistant gram-negative urinary tract infections (UTIs) is increasing, often requiring intravenous antimicrobial therapy. Oral fosfomycin is a recommended alternative agent for the treatment of cystitis caused by extended spectrum beta-lactamase (ESBL)-producing Escherichia coli (E. coli). The primary objective of this study is to evaluate the efficacy of fosfomycin in the treatment of UTIs at the Veterans Affairs Long Beach Healthcare System. The secondary objective is to assess the incidence of adverse drug reactions associated with fosfomycin. Methods This is a retrospective, single-center, cohort study. Patients who received fosfomycin between June 1st, 2015 – June 30th, 2020 were included. Data collection was completed by chart review through the Computerized Patient Record System (CPRS). Descriptive analysis was used to evaluate data. Treatment outcomes were analyzed using a composite of clinical and microbiological cure. Clinical cure was defined as resolution of UTI symptoms. Microbiological cure was defined as urine sterilization within 1 month after completing treatment course with fosfomycin. Results A total of 62 unique patients were evaluated in this study. The mean age was 71.9 years. 56 patients (90.3%) were male, 31 patients (50.0%) had an indwelling catheter present at the time of treatment, and 48 patients (77.4%) had the presence of genitourinary tract pathology that may increase the risk of developing UTIs. Majority of patients (50%) had a urine culture result positive for E. coli prior to treatment, of which 43.5% were ESBL-producing. 60 patients (96.8%) received more than 1 dose of Fosfomycin. Out of 29 patients who were eligible to be evaluated for clinical outcomes, 20 patients (68.9%) met a positive composite outcome of either microbiological cure, clinical cure, or both. 4 patients (6.5%) experienced an adverse drug reaction of diarrhea that was self-limited. Conclusion Fosfomycin is an effective and well-tolerated antimicrobial agent that may be considered for treatment of complicated UTIs without evidence of pyelonephritis or bacteremia caused by multi-drug resistant organisms in the veteran population. Disclosures All Authors: No reported disclosures

187. Vancomycin Plus Ceftaroline Salvage Therapy for Persistent Methicillin-Resistant Staphylococcus aureus Bacteremia

Background The preferred antibiotic salvage regimen for persistent methicillin-resistant Staphylococcus aureus bacteremia (pMRSAB) is unclear. Vancomycin plus ceftaroline (V/C) has demonstrated potent in vitro synergistic activity against MRSA; however, clinical data is limited. Thus, we sought to evaluate V/C salvage therapy for pMRSAB. Methods This was a single-center, retrospective cohort study of patients with MRSAB who received V/C salvage therapy between 1/1/2016-3/10/2021. Adult patients were included if blood cultures (BC) were positive for MRSA for ≥ 72 hours, received anti-MRSA monotherapy initially, and subsequently received V/C ≥ 24 hours. Patients were excluded if they received other anti-MRSA antibiotics within 72 hours of V/C initiation. The primary outcome was time to BC clearance following V/C initiation. Secondary outcomes included 90-day all-cause mortality, microbiological cure, 90-day MRSAB recurrence, and length of stay (LOS). Microbiological cure was defined as BC clearance. Results Of 178 patients identified, 20 were evaluated after inclusion and exclusion criteria were applied. Mean (SD) age and Pitt Bacteremia score were 38.5 (14.5) years and 4.2 (3.1), respectively. Most patients were male (70%), intravenous drug users (65%), and admitted to the intensive care unit (65%). The most common source was intravenous drug use (55%) and the majority had infective endocarditis (70%). All patients received infectious disease consultation and median (IQR) vancomycin AUC:MIC was 527 (454, 611). Source control, if possible, was obtained in most patients (55%). Median (IQR) time to bloodstream clearance from first positive BC and from when ceftaroline was initiated was 9.7 (8.4, 10.2) and 2.4 (1.5, 3.1) days, respectively. 90-day all-cause mortality, microbiological cure, and 90-day MRSAB recurrence occurred in 35%, 95%, and 5% of patients, respectively. Median (IQR) LOS was 25 (14.5, 32.0) days. Conclusion To our knowledge, this is the largest cohort to evaluate V/C for pMRSAB. Patients were medically complex; however, median time to MRSAB clearance following ceftaroline initiation was &lt; 2.5 days and microbiological cure was obtained in nearly all patients. V/C may represent a potential salvage regimen for pMRSAB. Disclosures Wesley D. Kufel, PharmD, Melinta (Research Grant or Support)Merck (Research Grant or Support)Theratechnologies, Inc. (Advisor or Review Panel member) Jeffrey Steele, Pharm.D., Paratek Pharmaceuticals (Advisor or Review Panel member)

190. Outcomes of Early Ceftaroline-based Combination Therapy for Methicillin-resistant Staphylococcus aureus Bacteremia

Background Monotherapy with vancomycin (VAN) or daptomycin (DAP) remains the guideline-driven standard of care for methicillin-resistant Staphylococcus aureus bacteremia (MRSA-B) despite concerns regarding efficacy. While combination therapy is often utilized as salvage treatment for persistent MRSA-B, growing data suggest a potential benefit of combination therapy with ceftaroline as initial therapy for MRSA-B. In light of these data, we updated practice guidance at our institution for management of MRSA-B in March 2020 to favor initial combination therapy with ceftaroline. Herein, we present an assessment of outcomes of patients with MRSA-B initiated on early combination therapy. Methods This was a single-center, retrospective, cohort study of adult patients admitted to the University of Virginia with MRSA-B between July 1, 2018 and February 28, 2021. Patients were considered to have received combination therapy if they received VAN or DAP plus ceftaroline (CPT) within 5 days of index blood culture, and monotherapy if during that period they received VAN and/or DAP alone. The primary outcome was a composite of persistent bacteremia, 30-day all-cause mortality, and 30-day bacteremia recurrence. Time to microbiological cure and safety outcomes were also assessed. A propensity score-weighted logistic regression was conducted. A post-hoc analysis of the primary composite outcome was performed in which patients were only deemed to have received combination therapy if it was started within 72 hours. Results Of 94 patients included, 57 received monotherapy (55 VAN, 2 DAP) and 37 received combination therapy with CPT (30 VAN, 7 DAP). There was no difference between groups for the primary composite outcome in the primary analysis (OR 2.7, 95% CI 0.95-7.72) or the post-hoc analysis (OR 2.37, 95% CI 0.68-8.22). Time to microbiological cure was not different between groups (mean difference 1.47, 95% CI 0.20-2.74). Safety outcomes were similar. Conclusion In this retrospective study, there was no clear benefit or harm of early initiation of combination therapy for MRSA-B. Additional study of initial combination therapy with ceftaroline is warranted given the small number of subjects in the study presented. Disclosures All Authors: No reported disclosures

Efficacy of doxycycline versus azithromycin for the treatment of rectal chlamydia: a systematic review and meta-analysis

Background Chlamydia trachomatis infection is the most common sexually transmitted infectious disease and carries a risk of complications. However, the optimal treatment for rectal chlamydial infection remains unclear. Objectives To compare the efficacy of doxycycline and azithromycin for the treatment of rectal chlamydia by undertaking a systematic review and meta-analysis of published data. Methods We searched PubMed, EMBASE, Cochrane Library, Web of Science and clinicaltrials.gov databases from inception to 7 July 2021 for randomized controlled trials (RCTs) and observational studies that compared the efficacy of doxycycline and single-dose azithromycin on rectal chlamydia cure rates. Data were synthesized using a random-effects model, and subgroup analysis was conducted. Results All included studies were conducted in developed countries. Two RCTs and nine observational studies, with a total of 2457 patients, were analysed. Doxycycline had a higher microbiological cure rate than azithromycin (risk ratio = 1.21; 95% CI = 1.15–1.28; P &lt; 0.05). Pooled results from two RCTs also revealed a higher microbiological cure rate for doxycycline than azithromycin (risk ratio = 1.27; 95% CI = 1.20–1.35; P &lt; 0.05). The results remained consistent in subgroups of different study designs, countries and sexes. Conclusions On the basis of our findings, we recommend doxycycline rather than azithromycin as a first-line treatment for rectal chlamydia in developed countries. More RCTs from developing countries are warranted.

Successful treatment with secnidazole for trichomoniasis in the setting of metronidazole hypersensitivity

Limited effective treatment options currently exist for trichomoniasis management among patients with metronidazole hypersensitivity. We report a patient with a documented history of metronidazole hypersensitivity who initially was treated with nitazoxanide but demonstrated clinical and microbiological failure. Secnidazole was subsequently used for treatment, which resulted in clinical and microbiological cure without observation of cross-reactivity. Secnidazole may represent a potential treatment option for trichomoniasis in patients with metronidazole hypersensitivity after consultation with an infectious disease specialist.