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.

Classification of Patient Recovery from COVID-19 Symptoms using Consumer Wearables and Machine Learning.

Current remote monitoring of COVID-19 patients relies on manual symptom reporting, which is highly dependent on patient compliance. In this research, we present a machine learning (ML)-based remote monitoring method to estimate patient recovery from COVID-19 symptoms using automatically collected wearable device data, instead of relying on manually collected symptom data. We deploy our remote monitoring system, namely eCOVID, in two COVID-19 telemedicine clinics. Our system utilizes a Garmin wearable and symptom tracker mobile app for data collection. The data consists of vitals, lifestyle, and symptom information which is fused into an online report for clinicians to review. Symptom data collected via our mobile app is used to label the recovery status of each patient daily. We propose a ML-based binary patient recovery classifier which uses wearable data to estimate whether a patient has recovered from COVID-19 symptoms. We evaluate our method using leave-one-subject-out (LOSO) cross-validation, and find that Random Forest (RF) is the top performing model. Our method achieves an F1-score of 0.88 when applying our RF-based model personalization technique using weighted bootstrap aggregation. Our results demonstrate that ML-assisted remote monitoring using automatically collected wearable data can supplement or be used in place of manual daily symptom tracking which relies on patient compliance.

Persistent Smell Loss Following Undetectable SARS-CoV-2.

The association of smell and taste loss with COVID-19 has been well demonstrated with high prevalence rates. In certain cases, chemosensory loss may be the only symptom of COVID-19 and may linger while other symptoms have resolved. The significance of persistent smell and taste loss and its relationship to ongoing viral shedding has yet to be investigated. In this cross-sectional study, of the 316 laboratory test-confirmed COVID-19 cases at our institution, 46 had subsequent test-based confirmation of viral clearance with 2 consecutive negative RT-PCR test results (reverse transcriptase polymerase chain reaction). Olfactory dysfunction was reported by 50% of the patients (23 of 46), with 78% (18 of 23) having subjective persistent smell loss despite negative RT-PCR test results. These preliminary data demonstrate the persistence of self-reported smell loss despite otherwise clinical resolution and undetectable nasal viral RNA.

Multidrug resistant bacteriuria before percutaneous nephrolithotomy predicts for postoperative infectious complications.

BACKGROUND AND PURPOSE: Multidrug resistant (MDR) uropathogens are increasing in prevalence and may contribute to significant morbidity after percutaneous nephrolithotomy (PCNL). We investigate the presence of MDR bacteriuria and occurrence of postoperative infectious complications in patients who underwent PCNL at our institution. METHODS: Retrospective review was performed of 81 patients undergoing PCNL by a single surgeon (RLS) between 2009 and 2013. Patient demographics, comorbidities, stone parameters on imaging, and microbial data were compiled. MDR organisms were defined as resistant to three or more of the American Urological Association Best Practice Statement antimicrobial classes for PCNL. Postoperative complications were graded by Clavien score and European Association of Urology infection grade. Univariate comparisons were analyzed between patients with and without a postoperative infectious complication. Multivariate logistic regression was performed to determine significant predictor variables for postoperative infectious complications. RESULTS: Of the 81 patients undergoing PCNL, 41/81 (51%) had positive preoperative urine culture, 24/81 (30%) had positive MDR urine culture, and 16/81 (19%) had a postoperative infectious complication. Multivariate analysis revealed a positive preoperative MDR urine culture significantly increased the risk of postoperative infectious complication (odds ratio [OR]=4.89, 95% confidence interval [CI] 1.134-17.8, P=0.016). The presence of more than one access tract during PCNL also predicted for infectious complications (OR=7.5, 95% CI 2.13-26.4, P=0.003) Of the 16 patients with a postoperative infection 3 (18%) had postoperative urine cultures discordant with the preoperative urine cultures. CONCLUSIONS: Our institution demonstrated a relatively high prevalence of MDR bacteriuria in patients undergoing PCNL and that MDR is a significant risk factor for postoperative infectious complications despite appropriate preoperative antibiotics. Further investigations regarding prophylaxis modalities and infection prevention strategies are needed.

Systematic review and meta-analysis on management of hemodialysis catheter-related bacteremia.

Hemodialysis catheter-related bacteremia is a common clinical problem with several management options. We performed a systematic review and meta-analysis to determine cure proportions with systemic antibiotics, antibiotic lock solution, and guidewire exchange. We searched databases and registries; conference proceedings from relevant medical societies; and article reference lists. Data regarding management approach, cure, follow-up, recurrence, complications, and microbiology were abstracted and pooled from 28 selected publications. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated from a mixed effects logistic regression model. In total, 1596 patients with tunneled hemodialysis catheter-related bacteremia were divided into groups on the basis of treatment with systemic antibiotics (n=697), antibiotic lock solution (n=546), or guidewire exchange (n=353). Antibiotic lock solution and guidewire exchange had similar cure proportions that were superior to systemic antibiotics alone (OR, 2.08; 95% CI, 1.25 to 3.45; P<0.01 for antibiotic lock solution; OR, 2.88; 95% CI, 1.82 to 4.55; P<0.001 for guidewire exchange versus systemic antibiotics). Cure proportions were highest for coagulase-negative staphylococci followed by gram-negative rods and Staphylococcus aureus. Among S. aureus infections, guidewire exchange led to a higher cure proportion than systemic antibiotics or antibiotic lock solution (OR, 3.33; 95% CI, 1.17 to 9.46; P=0.02; OR, 4.72; 95% CI, 1.79 to 12.46; P=0.002, respectively). Thus, results of this study suggest that tunneled hemodialysis catheter-related bacteremia should be treated with either guidewire exchange or antibiotic lock solution. Future studies should address prospectively whether one strategy is better than the other overall and for specific pathogens.

Pharmacotherapy of cryptococcosis.

Cryptococcus neoformans is an opportunistic fungal pathogen that causes central nervous system and pulmonary disease among immunocompromised patients. Recent studies highlight the high incidence of cryptococcosis among patients in certain resource-poor areas, where there is also a high incidence of AIDS. Despite the availability of antifungal agents with anticryptococcal activity, the mortality and treatment-failure rates associated with cryptococcosis remain unacceptably high. This article reviews current treatment strategies and the basis for these strategies, as well as prospects for future approaches to the treatment of cryptococcosis.