This article is for people interested in the latest ID/stewardship publications. Here are our picks for the top new ID/stewardship journal articles trending on Twitter from October 2018 – in case you missed it!
[Last updated: 6 November 2018]
In this monthly column two pharmacists that are twitter enthusiasts (@ABsteward [B.G.] & @IDstewardship [T.P.G.]) identify recently published articles and provide summaries to help you keep an eye on the leading edge of science in the fields of antimicrobial stewardship & infectious diseases.
The following are new publications we found most interesting or noteworthy in October of 2018…
Effect and Safety of Meropenem–Vaborbactam versus Best-Available Therapy in Patients with Carbapenem-Resistant Enterobacteriaceae Infections: The TANGO II Randomized Clinical Trial | Infect Dis Ther.
Treatment options for carbapenem-resistant Enterobacteriaceae (CRE) infections are limited. Meropenem-vaborbactam (M-V) is a new β-lactam/ β-lactamase inhibitor combination that restores the potency of meropenem in Klebsiella pneumoniae carbapenemase (KPC)-producing CRE.
TANGO II is a Phase 3, randomized, prospective, multicenter, multinational, open-label trial of 72 patients who were randomized 2:1 to monotherapy with M-V (2g/2g every 8h as a 3h infusion) or Best Available Therapy (BAT) for 7–14 days . BAT included any of the following as monotherapy or in combination: polymyxins, carbapenems, aminoglycosides, or tigecycline; or monotherapy with ceftazidime-avibactam. The study concluded that monotherapy with M-V for CRE infection was associated with increased clinical cure, decreased mortality, and reduced nephrotoxicity compared with BAT.
Accompanying editorial: https://link.springer.com/article/10.1007/s40121-018-0215-0
Effect of Increased Daily Water Intake in Premenopausal Women With Recurrent Urinary Tract Infections A Randomized Clinical Trial | JAMA
Women with recurrent cystitis are often counseled about behavioral interventions prior to considering the use of antimicrobial therapy as an infection prevention strategy. One such antimicrobial-sparing strategy is to increase hydration, however previously published evidence to support such strategy is sparse.
A randomized, open-label, controlled, trial of 140 healthy women with recurrent cystitis (≥3 episodes in past year) were randomly assigned to drink 1.5 L of water daily or no additional fluids for 12 months. This was in addition to their usual fluid intake. Women who consumed additional water had an approximately 50% reduction in number of cystitis episodes in the year after randomization and were prescribed fewer antibiotics. Increasing daily water intake protects against recurrent cystitis in premenopausal women experiencing recurrent cystitis who drink low volumes of total fluid daily.
Isavuconazole versus caspofungin in the Treatment of Candidemia and Other Invasive Candida Infections: The ACTIVE Trial | CID.
Invasive candida infections remain a significant source of patient morbidity and mortality. Despite advances in antifungal therapy, mortality among patients with invasive candidiasis is still high.
ACTIVE was a phase 3, randomized, double-blind, double-dummy, multicenter, noninferiority study of IV isavuconazole followed by oral isavuconazole compared with IV caspofungin followed by oral voriconazole as initial therapy for candidemia and other forms of invasive candidiasis. The study did not demonstrate the non-inferiority of isavuconazole to caspofungin for primary treatment of invasive candidiasis (successful overall response at end of IV therapy [EOIVT] 60.3% in the isavuconazole arm and 71.1.% in the caspofungin arm, -10.8). The secondary endpoints of all-cause mortality and safety were similar between arms, while median time to clearance of the bloodstream was comparable in both groups. An intriguing finding for this study is that isavuconazole was favored as the oral step-down therapy when compared to voriconazole. It may very well be a reasonable treatment option for fluconazole-resistant isolates, drug-interactions and other toxicities.
Cefiderocol versus imipenem-cilastatin for the treatment of complicated urinary tract infections caused by Gram-negative uropathogens: a phase 2, randomised, double-blind, non-inferiority trial | Lancet Infect Dis.
The availability of effective therapies against multidrug-resistant Gram-negative bacteria is an important unmet medical need. Cefiderocol, the first siderophore antibiotic to reach late-stage development, it is stable against all classes of β-lactamases.
This is a randomised, phase 2, multicenter, multinational, double-blind, parallel-group, non-inferiority trial of adult patients admitted to hospital with a clinical diagnosis of complicated urinary tract infection with or without pyelonephritis or those with acute uncomplicated pyelonephritis randomly assigned (2:1) to receive 1 h intravenous infusions of cefiderocol (2 g every 8 hours) or imipenem-cilastatin (1 g every 8 hours) for 7–14 days. Patients were excluded if they had pathogens known to be carbapenem resistant. Intravenous infusion of cefiderocol was non-inferior compared with imipenem-cilastatin for the treatment of complicated urinary tract infection in people with multidrug-resistant Gram-negative infections. The results of this study will provide the basis for submission of a New Drug Application to the US Food and Drug Administration.
Single-dose versus 7-day-dose metronidazole for the treatment of trichomoniasis in women: an open-label, randomised controlled trial | Lancet Infect Dis.
Among women, trichomoniasis is the most common non-viral sexually transmitted infection worldwide. A single dose of oral metronidazole has long been favored over 7-day-dose for the treatment of trichomoniasis.
This was a multicentre, open-label, randomised controlled trial comparing the efficacy of a single-2 g dose of oral metronidazole with 7-day-dose oral metronidazole (500 mg taken twice daily) for treatment of trichomoniasis among HIV-uninfected, non-pregnant women. Patients in the 7-day group were less likely to be T. vaginalis positive at test-of-cure than those in the single-dose group (11% vs. 19%, RR 0.55, 95% CI 0.34 to 0.70, p<0.0001). Most women who enrolled were African American (96%) and the median age was 27 years. Adherence to treatment was lower in the 7-day-dose group than in the single-dose group (96% vs. 99% respectively, p=0.006). The study findings add to the evidence that 7-day-dose metronidazole is superior to single-dose metronidazole for the treatment of trichomoniasis in women, irrespective of bacterial vaginosis status.
Role of Early De-escalation of Antimicrobial Therapy on Risk of Clostridioides difficile Infection following Enterobacteriaceae Bloodstream Infections | CID
The association between the use of broad-spectrum antimicrobial agents and Clostridioides difficile infection (CDI) has been well-established.There is a paucity of data on the effect of early de-escalation of antimicrobial therapy on rates of CDI.
This is a large retrospective cohort study for adults hospitalized for >48 hours for treatment of Enterobacteriaceae bloodstream infections (BSI) to evaluate impact of de-escalation from antipseudomonal beta-lactams (APBL) within 48 hours of Enterobacteriaceae BSI on 90-day risk of CDI. The study found that Incidence of CDI among patients with Enterobacteriaceae BSI, who received >48 hours was more than 3 fold higher than those who received ≤48 hours of APBL (NNT=19). After adjustment for propensity empirical use of APBL for >48 hours and end-stage renal disease were independently associated with higher risk of CDI. Early de-escalation of APBL may reduce the incidence of CDI in hospitalized adults with Enterobacteriaceae BSI.
Procalcitonin-guided antibiotic treatment in patients with positive blood cultures: A patient-level meta-analysis of randomized trials | CID
Several trials have now investigated the effects of procalcitonin (PCT)-guided use of antibiotics in patients with respiratory infections and sepsis. Whether PCT-guided antibiotic management in patients with positive blood cultures is safe remains understudied and physicians may be reluctant to reduce treatment duration in this patient population based upon PCT.
This patient level meta-analysis investigated the effects of PCT-guided antibiotic management in patients with bacteremia overall, stratifying patients by type of pathogen. The pooled analysis demonstrated that PCT-guided antibiotic management significantly decreased antibiotic treatment duration (adjusted difference -2.86 days, 95%CI -4.88 to -0.84, p=0.006) without an apparent increase in mortality in patients with bacteremia. Subgroup analysis revealed a more pronounced decrease in duration of antibiotic therapy in patients with pneumococcal pneumonia and E. coli urogenital infections.
Ceftolozane-tazobactam for the treatment of multidrug-resistant Pseudomonas aeruginosa infections: A multicenter study | OFID
Ceftolozane-tazobactam (C/T) is indicated for the treatment of complicated urinary tract infections and complicated intra-abdominal infections. Clinical evidence supporting the use of C/T for treatment of multidrug-resistant (MDR) Pseudomonas aeruginosa infections is lacking.
This was a multicenter, retrospective observational study of adult patients who received C/T at least 24 for MDR Pseudomonas aeruginosa infections from any source between December 2014 and February 2018 at 20 health systems in the United States. The study found that delayed initiation of C/T was common with therapy started a median of 9 days after culture collection. Mortality occurred in 19% of patients, clinical success and microbiological cure were 73.7% and 70.7%, respectively. On multivariable regression analysis, starting C/T within 4 days of culture collection was associated with survival, clinical success, and microbiological cure for MDR Pseudomonas aeruginosa infections. C/T appeared to be effective in the treatment of MDR Pseudomonas aeruginosa infections, particularly when initiated early after the onset of infection.
Implementation of Rapid Diagnostic Testing without Active Stewardship Team Notification for Gram-Positive Blood Cultures in a Community Teaching Hospital | AAC
Rapid diagnostics tests (RDTs) for managing infectious diseases have revolutionized the field, but their impact can vary greatly depending on the practice setting and support system in place.
In this retrospective quasi-experimental study of 252 adult inpatients in a community hospital with positive blood cultures for Gram-positive cocci in clusters, investigators found that without active stewardship intervention the median time to appropriate therapy (15 versus 0 hours, P < 0.001) and length of stay for coagulase-negative Staphylococci (10.5 versus 7.7 days, P = 0.015) was improved when RDT was used. This data supports the notion that RDTs are powerful tools for managing infectious diseases and may be of great value outside of this setting and without active stewardship team engagement.
ADDITIONAL NEW & NOTABLE PUBLICATIONS
Suboptimal Clinical Response Rates with Newer Antibiotics Among Patients with Moderate Renal Impairment: Review of the Literature and Potential Pharmacokinetic and Pharmacodynamic Considerations for Observed Findings | Pharmacotherapy
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