Refractory Pseudomonas aeruginosa infections treated with phage PASA16: A compassionate use case series.

BACKGROUND: A growing number of compassionate phage therapy cases were reported in the last decade, with a limited number of clinical trials conducted and few unsuccessful clinical trials reported. There is only a little evidence on the role of phages in refractory infections. Our objective here was to present the largest compassionate-use single-organism/phage case series in 16 patients with non-resolving Pseudomonas aeruginosa infections. METHODS: We summarized clinical phage microbiology susceptibility data, administration protocol, clinical data, and outcomes of all cases treated with PASA16 phage. In all intravenous phage administrations, PASA16 phage was manufactured and provided pro bono by Adaptive Phage Therapeutics. PASA16 was administered intravenously, locally to infection site, or by topical use to 16 patients, with data available for 15 patients, mainly with osteoarticular and foreign-device-associated infections. FINDINGS: A few minor side effects were noted, including elevated liver function enzymes and a transient reduction in white blood cell count. Good clinical outcome was documented in 13 out of 15 patients (86.6%). Two clinical failures were reported. The minimum therapy duration was 8 days with a once- to twice-daily regimen. CONCLUSIONS: PASA16 with antibiotics was found to be relatively successful in patients for whom traditional treatment approaches have failed previously. Such pre-phase-1 cohorts can outline potential clinical protocols and facilitate the design of future trials. FUNDING: The study was funded in part by The Israeli Science Foundation IPMP (ISF_1349/20), Rosetrees Trust (A2232), United States-Israel Binational Science Foundation (2017123), and the Milgrom Family Support Program.

Microbiological and clinical changes following the transition to the 2010 revised CLSI breakpoints for extended-spectrum cephalosporin in Enterobacterales.

In 2016, our laboratory adopted the 2010 CLSI extended-spectrum cephalosporins (ESC) breakpoint criteria in Enterobacterales. ESBL testing had continued in Blood cultures but discontinued in General Cultures. The aims of this study were to examine the effect of this transition on (1) the resistance rates to ESC; (2) the consumption of parenteral ß-lactam antimicrobials, and (3) the therapeutic use of ESC and the outcome of patients infected by ESBL-producing Enterobacterales. In K. pneumoniae and E. coli, the ESC resistance rates had increased, declined or remained unchanged in Urine, General and Blood cultures, respectively. In P. mirabilis, the resistance rates declined for ceftazidime but remained unchanged for ceftriaxone. Carbapenem consumption had not replaced ESC, but the consumption of piperacillin-tazobactam had increased. The use of ESC in suspected ESBL infections had increased slightly, without effect on clinical outcome.

The implementation of rapid microbial identification via MALDI-ToF reduces mortality in gram-negative but not gram-positive bacteremia.

Our goals were to study the effect of rapid microbial identification (RMI) of positive blood culture on patient's outcome and to identify specific microbiological characteristics related to clinical benefit of RMI. This was a retrospective-cohort study of hospitalized, adult patients with bacteremia. The outcome of patients with bacteremia episodes was compared before vs. after the initiation of RMI. RMI was done by matrix-assisted laser desorption/ionization time-of-flight testing of microcolonies. The study included 1460 and 2710 cases in the pre- and post-intervention periods, respectively. There were similar rates of gram-negative, gram-positive, anaerobes, and polymicrobial infections, but higher rate of contaminants in the intervention period (39.9 vs. 43.7%, p = 0.019). The median time-to-identification decreased from 47.5 to 21.3 h (p < 0.001). Post-intervention, the median LOS declined from 10.83 to 9.79 days (p = 0.016), the rate of ICU transfer declined from 13.8 to 11.6% (p = 0.054), and the mortality rate declined from 20.9 to 18.3% (p = 0.047). The improvement in outcome variables remained statistically significant in multivariate analysis when performed for all episodes and non-contaminants but not for contaminants. The mortality declined in gram-negative bacteremia (20% vs. 15.5%, p = 0.005 in multivariate analysis) but not in gram-positive bacteremia (18.1% vs. 18.5%). RMI reduces mortality from gram-negative but not gram-positive bacteremia.