Daily Fosfomycin Versus Levofloxacin for Complicated Urinary Tract Infections

Concerns over resistance and safety have been identified in the current treatment regimen for complicated urinary tract infections. Fosfomycin is a drug that is routinely used for the treatment of uncomplicated cystitis. This study shows that fosfomycin could be an oral alternative as step-down therapy for the treatment of complicated urinary tract infections, with a clinical cure rate comparable to levofloxacin but a lower microbiological success rate 3 weeks from start of antibiotics

Staphylococcus simulans: A rare uropathogen

Urinary tract infections (UTIs) are clinically and economically burdensome. Gram positive causative uropathogens are rare, and Staphylococcus simulans has infrequently been isolated as a causative agent for UTIs. Here, we present two cases of S. simulans causing complicated urinary tract infections

Jail, An Unappreciated Medical Home: Assessing the Feasibility of a Strengths-based Case Management Intervention to Improve the Care Retention of HIV-infected Persons Once Released from Jail

Background Linkage to and retention in care for US persons living with HIV (PLWH) after release from jail usually declines. We know of no rigorously evaluated behavioral interventions that can improve this. We hypothesized that a strengths-based case management intervention that we developed for PLWH leaving jail would increase linkage/retention in care (indicated by receipt of laboratory draws) and a suppressed HIV viral load (VL) in the year following release. Methods and findings We conducted a quasi-experimental feasibility study of our intervention for PLWH jailed in Atlanta. We recruited 113 PLWH in jail starting in 2014. “SUCCESS” (Sustained, Unbroken Connection to Care, Entry Services, and Suppression) began in jail and continued post-release. Subjects who started the intervention but subsequently began long-term incarcerations were excluded from further analysis. Persons who were retained in the intervention group were compared to contemporaneously incarcerated PLWH who did not receive the intervention. Identities were submitted to an enhanced HIV/AIDS reporting system (eHARS) at the state health department to capture all laboratories drawn. Both community engagement and care upon jail return were assessed equally. For 44 intervention participants released to Atlanta, 50% of care occurred on subsequent jail stays, as documented with EventFlow software. Forty-five receiving usual services only were recruited for comparison. By examining records of jail reentries, half of participants and 60% of controls recidivated (range: 1–8 returns). All but 6 participants in the intervention and 9 subjects in the comparison arm had ≥1 laboratory recorded in eHARS post-release. Among the intervention group, 52% were retained in care (i.e., had two laboratory studies, \u3e = 3 months apart), versus 40% among the comparison group (OR = 1.60, 95% CI (0.71, 3.81)). Both arms showed improved viral load suppression. Conclusions There was a trend towards increased retention for PLWH released from jail after SUCCESS, compared to usual services. Measuring linkage at all venues, including jail-based clinics, fully captured engagement for this frequently recidivating population

Participant flow diagram.

<p>Participant flow diagram.</p

Daily fosfomycin versus levofloxacin for complicated urinary tract infections

ABSTRACT Fosfomycin, approved in the United States only for cystitis, is an attractive alternative for oral treatment of outpatient complicated urinary tract infections (cUTIs) as it has antimicrobial activity against most common uropathogens. The study was a multicenter, randomized, open-label pragmatic superiority clinical trial evaluating the efficacy of oral fosfomycin versus oral levofloxacin strategies in cUTIs (FOCUS study). The trial compared two strategies for initial or step-down oral therapy of cUTI without bacteremia after 0–48 hours of parenteral antibiotic therapy. Subjects were assigned to 3 g of fosfomycin or 750 mg (or dose adjusted for kidney function) of levofloxacin daily for 5–7 days. Clinical and microbiological cures were assessed at the end of therapy (EOT) and test of cure (TOC) (approximately 21 days from the start of antibiotics). The trial did not meet accrual goals; thus, the results were descriptive. Only 51 subjects were included in the microbiological intention-to-treat population. The subjects were mainly females (76%), with a mean age of 46.7 years (standard deviation [SD] = 20.8) and acute pyelonephritis (88%). At the end of therapy, clinical cure remained similar (69% and 68% for fosfomycin and levofloxacin strategies, respectively), and microbiological success was 100% for both strategies. At the test of cure, clinical cure was similar (84% and 86% in the fosfomycin and levofloxacin strategies, respectively); however, a numerically lower microbiological success was observed for fosfomycin (69% compared to 84% for levofloxacin). These limited data suggest that fosfomycin could be an oral alternative as a step-down therapy for the treatment of cUTIs (registry number NCT 03697993). IMPORTANCE Concerns over resistance and safety have been identified in the current treatment regimen for complicated urinary tract infections. Fosfomycin is a drug that is routinely used for the treatment of uncomplicated cystitis. This study shows that fosfomycin could be an oral alternative as step-down therapy for the treatment of complicated urinary tract infections, with a clinical cure rate comparable to levofloxacin but a lower microbiological success rate 3 weeks from start of antibiotics

Demographic, psychological, and medical characteristics of SUCCESS¹ study participants², Atlanta, GA, 2014–2015 (N = 89).

<p>Demographic, psychological, and medical characteristics of SUCCESS<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0191643#t001fn001" target="_blank">¹</a> study participants<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0191643#t001fn002" target="_blank">²</a>, Atlanta, GA, 2014–2015 (N = 89).</p

Linkage and retention of SUCCESS¹ study participants, HIV infected persons released from Fulton County Jail, Atlanta, GA, 2014–2016².

<p>Linkage and retention of SUCCESS<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0191643#t002fn001" target="_blank">¹</a> study participants, HIV infected persons released from Fulton County Jail, Atlanta, GA, 2014–2016<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0191643#t002fn002" target="_blank">²</a>.</p

Schematic for SUCCESS study data collection on HIV infected persons released from Fulton County Jail, Atlanta, GA, 2014–2016.

<p>• SUCCESS is Sustained, Unbroken, Connection to Care, Entry Services, and Suppression; strengths-based case management intervention implemented among individuals released from Fulton County Jail, compared with usual jail discharge services. • This figure demonstrates the data collection structure and yield from HIV care sites identified by intervention group study participants at enrollment, as compared with the sites where care was truly received over the course of one year following release, according to state HIV care registry data.</p

Trajectory of HIV care and recidivism events for SUCCESS¹ study participants after index jail stay, Fulton County Jail, Atlanta, GA, 2014–2016.

<p>• In each panel, the horizontal axis displays time since initial release. • Each subject has a row entry, with red intervals representing re-entries to an area jail after the initial release from the enrollment jail stay. • Laboratory data were not collected by the research team on an individual basis for the comparison group, and are thus not reflected.</p

Trajectory of HIV care and follow-up survey events for SUCCESS participants after index release from Fulton County Jail (FCJ), Atlanta, GA, 2014–2016.

<p>• SUCCESS is Sustained, Unbroken, Connection to Care, Entry Services, and Suppression; strengths-based case management intervention implemented among individuals released from Fulton County Jail, compared with usual jail discharge services. • This figure demonstrates an overview of returns to jail and lab draws for participants. • Event Flow visualization aligns like events; in this case, releases, return visits, and labs are grouped together based on when they occurred. • Time zero for each intervention participant is their initial release, marked in blue. • Thereafter, like events are grouped together temporally over the course of one year of follow-up. • For interval events such as returns to jail, the length of the intervals represents the mean duration of the grouped events. • For point events such as laboratory draws, periods between the aggregated point events represent the mean length of time from any previous point event. • Our aim was to begin the intervention in jail and complete it after release to the community; however, in practice, the intervention may have been incomplete before a participant returned to jail after their initial release.</p