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.

A panel of diverse Klebsiella pneumoniae clinical isolates for research and development.

Klebsiella pneumoniae are a leading cause of healthcare-associated infections worldwide. In particular, strains expressing extended-spectrum ß-lactamases (ESBLs) and carbapenemases pose serious treatment challenges, leading the World Health Organization (WHO) to designate ESBL and carbapenem-resistant Enterobacteriaceae as 'critical' threats to human health. Research efforts to combat these pathogens can be supported by accessibility to diverse and clinically relevant isolates for testing novel therapeutics. Here, we describe a panel of 100 diverse K. pneumoniae isolates that are publicly available to assist the research community in this endeavour. Whole-genome sequencing (WGS) was performed on 3878 K. pneumoniae clinical isolates housed at the Multidrug-Resistant Organism Repository and Surveillance Network. The isolates were cultured from 63 facilities in 19 countries between 2001 and 2020. Core-genome multilocus sequence typing and high-resolution single-nucleotide polymorphism-based phylogenetic analyses captured the genetic diversity of the collection and were used to select the final panel of 100 isolates. In addition to known multidrug-resistant (MDR) pandemic lineages, the final panel includes hypervirulent lineages and isolates with specific and diverse resistance genes and virulence biomarkers. A broad range of antibiotic susceptibilities, ranging from pan-sensitive to extensively drug-resistant isolates, are described. The panel collection, and all associated metadata and genome sequences, are available at no additional cost and will be an important resource for the research community and for the design and development of novel antimicrobial agents and diagnostics against this important pathogen.

The Emergence and Persistence of Candida auris in Western New York With No Epidemiologic Links: A Failure of Stewardship?

Reports of Candida auris infection in patients without epidemiologic links to prior outbreaks are scarce. We describe the genomic epidemiology of such a case in Western New York. Before emergence, the patient received >60 days of excess antibiotics. Candida auris was recovered on near-patient surfaces after enhanced terminal cleanings.

Benefit and cost of repeating a severe acute respiratory coronavirus virus 2 (SARS-CoV-2) polymerase chain reaction (PCR) test after the second day of hospitalization in five hospitals during various community prevalences and vaccination rates.

At our hospital, universal severe acute respiratory coronavirus virus 2 (SARS-CoV-2) polymerase chain reaction (PCR) testing was performed upon admission and again after 2 inpatient days. As community-wide prevalence, admission, and vaccination rates varied, the number needed to benefit fluctuated between 16 and 769 and the cost per additional detection fluctuated between $800 and $29,400. These 2 metrics were negatively associated with new hospital admissions. No other community indicator was associated with the number needed to benefit and cost per additional detection.

Prevalence of comorbidities and symptoms stratified by severity of illness amongst adult patients with COVID-19: a systematic review.

Introduction: We performed a systematic review of comorbidities and symptoms of adult patients with coronavirus disease 2019 (COVID-19) to evaluate comorbidities, symptoms, and severity. Material and methods: We searched databases and extracted comorbidities and symptoms from the included studies. We stratified the similar signs and symptoms in groups and on the basis of severity and compared them with stratified analysis. Individual case reports and case series with < 5 patients were excluded. Results: A total of 163 studies with 43,187 patients were included. Mean age was 54.6 years. There were significantly fewer women in the study (43.9% vs. 56.1%, p < 0.0001). Prevalent cardiovascular comorbidities were hypertension (31.9%), obesity (27.9%), hyperlipidemia (26.4%), smoking (18.9%), diabetes mellitus (17.2%), atherosclerotic disease (9.2%) and arrhythmia (5.0%). The most frequently reported constitutional symptoms of COVID-19 were fever (73.9%), fatigue (33.4%), malaise (29.9%), myalgia and/or arthralgia (19.2%), generalized weakness (19.0%), and chills (11.3%). For the cardiovascular system, chest pain and/or tightness were most often reported (19.6%), followed by palpitations (5.2%). Hypertension and diabetes were common in severe disease. Obesity and congestive heart failure were not observed in any non-severe cases. Severe cases compared to non-severe cases more frequently had fever (87.8% vs. 58.5%, p < 0.001), shortness of breath (47.4% vs. 20.6%, p < 0.001), cough (66.8% vs. 62.9%, p < 0.001), sputum production (35.4% vs. 26.5%, p < 0.001) and rhinorrhea (32.2% vs. 7.3%, p < 0.001). Conclusions: Hypertension, diabetes, and atherosclerotic diseases are common comorbidities across the world, with obesity as the second most common in the US and more common in men.

Infection preventionist staffing levels and rates of 10 types of healthcare-associated infections: A 9-year ambidirectional observation.

OBJECTIVE: To quantitatively evaluate relationships between infection preventionists (IPs) staffing levels, nursing hours, and rates of 10 types of healthcare-associated infections (HAIs). DESIGN AND SETTING: An ambidirectional observation in a 528-bed teaching hospital. PATIENTS: All inpatients from July 1, 2012, to February 1, 2021. METHODS: Standardized US National Health Safety Network (NHSN) definitions were used for HAIs. Staffing levels were measured in full-time equivalents (FTE) for IPs and total monthly hours worked for nurses. A time-trend analysis using control charts, t tests, Poisson tests, and regression analysis was performed using Minitab and R computing programs on rates and standardized infection ratios (SIRs) of 10 types of HAIs. An additional analysis was performed on 3 stratifications: critically low (2-3 FTE), below recommended IP levels (4-6 FTE), and at recommended IP levels (7-8 FTE). RESULTS: The observation covered 1.6 million patient days of surveillance. IP staffing levels fluctuated from ≤2 IP FTE (critically low) to 7-8 IP FTE (recommended levels). Periods of highest catheter-associated urinary tract infection SIRs, hospital-onset Clostridioides difficile and carbapenem-resistant Enterobacteriaceae infection rates, along with 4 of 5 types of surgical site SIRs coincided with the periods of lowest IP staffing levels and the absence of certified IPs and a healthcare epidemiologist. Central-line-associated bloodstream infections increased amid lower nursing levels despite the increased presence of an IP and a hospital epidemiologist. CONCLUSIONS: Of 10 HAIs, 8 had highest incidences during periods of lowest IP staffing and experience. Some HAI rates varied inversely with levels of IP staffing and experience and others appeared to be more influenced by nursing levels or other confounders.

Effectiveness of various cleaning strategies in acute and long-term care facilities during novel corona virus 2019 disease pandemic-related staff shortages.

BACKGROUND: Cleanliness of hospital surfaces helps prevent healthcare-associated infections, but comparative evaluations of various cleaning strategies during COVID-19 pandemic surges and worker shortages are scarce. PURPOSE AND METHODS: To evaluate the effectiveness of daily, enhanced terminal, and contingency-based cleaning strategies in an acute care hospital (ACH) and a long-term care facility (LTCF), using SARS-CoV-2 RT-PCR and adenosine triphosphate (ATP) assays. Daily cleaning involved light dusting and removal of visible debris while a patient is in the room. Enhanced terminal cleaning involved wet moping and surface wiping with disinfectants after a patient is permanently moved out of a room followed by ultraviolet light (UV-C), electrostatic spraying, or room fogging. Contingency-based strategies, performed only at the LTCF, involved cleaning by a commercial environmental remediation company with proprietary chemicals and room fogging. Ambient surface contamination was also assessed randomly, without regard to cleaning times. Near-patient or high-touch stationary and non-stationary environmental surfaces were sampled with pre-moistened swabs in viral transport media. RESULTS: At the ACH, SARS-CoV-2 RNA was detected on 66% of surfaces before cleaning and on 23% of those surfaces immediately after terminal cleaning, for a 65% post-cleaning reduction (p = 0.001). UV-C enhancement resulted in an 83% reduction (p = 0.023), while enhancement with electrostatic bleach application resulted in a 50% reduction (p = 0.010). ATP levels on RNA positive surfaces were not significantly different from those of RNA negative surfaces. LTCF contamination rates differed between the dementia, rehabilitation, and residential units (p = 0.005). 67% of surfaces had RNA after room fogging without terminal-style wiping. Fogging with wiping led to a -11% change in the proportion of positive surfaces. At the LTCF, mean ATP levels were lower after terminal cleaning (p = 0.016). CONCLUSION: Ambient surface contamination varied by type of unit and outbreak conditions, but not facility type. Removal of SARS-CoV-2 RNA varied according to cleaning strategy. IMPLICATIONS: Previous reports have shown time spent cleaning by hospital employed environmental services staff did not correlate with cleaning thoroughness. However, time spent cleaning by a commercial remediation company in this study was associated with cleaning effectiveness. These findings may be useful for optimizing allocation of cleaning resources during staffing shortages.

The rationale for including osteopathic manipulative treatment in the management of infections: a hermeneutic review.

INTRODUCTION: As the prevalence of drug-resistant infections continues to outpace the development of new antibiotics, we must explore all reasonable options for enhancing the effectiveness of existing anti-infectives. The emergence of novel pathogens without initial drug treatments or vaccines, typified by the severe acute respiratory syndrome coronavirus-2 pandemic, further underscores the need for non-pharmacologic adjunctive measures for infection management. Osteopathic manipulative treatment (OMT) may represent such an adjunct. AREAS COVERED: PubMed, CINAHL, Google Scholar, Cochrane databases and relevant chapters of major osteopathic texts were searched for animal experiments, case reports, observational studies, non-randomized, and randomized trials pertaining to infection, OMT, and the complications or safety of OMT. OMT was associated with one or more of the following: decreased bacterial colony counts in lung tissue; changes in immunologic profiles manifested by significant differences dendritic cells and levels of IL-8, MCP-1, MIP-1a, and G-CSF; shorter durations of IV antibiotics; decreased length of hospitalization; decreased rates of respiratory failure and death; decreased post-surgical lengths of stay; and enhanced patient satisfaction. EXPERT OPINION: Preliminary, lower-grade evidence suggests that OMT can improve some infection-related outcomes, and is safe. The role of OMT in infection management should undergo further controlled trials without delay.

Emergence of the E484K Mutation in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Lineage B.1.1.345 in Upstate New York.

A severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B.1.1.345 variant carrying the E484K mutation was detected in 4 patients with no apparent epidemiological association from a hospital network in upstate New York. Subsequent analysis identified an additional 11 B.1.1.345 variants from this region between December 2020 and February 2021.

A panel of diverse Pseudomonas aeruginosa clinical isolates for research and development.

OBJECTIVES: Pseudomonas aeruginosa is a leading cause of community- and hospital-acquired infections. Successful treatment is hampered by its remarkable ability to rapidly develop resistance to antimicrobial agents, primarily through mutation. In response, WHO listed carbapenem-resistant P. aeruginosa as a Priority 1 (Critical) pathogen for research and development of new treatments. A key resource in developing effective countermeasures is access to diverse and clinically relevant strains for testing. Herein we describe a panel of 100 diverse P. aeruginosa strains to support this endeavour. METHODS: WGS was performed on 3785 P. aeruginosa isolates in our repository. Isolates were cultured from clinical samples collected from healthcare facilities around the world between 2003 and 2017. Core-genome MLST and high-resolution SNP-based phylogenetic analyses were used to select a panel of 100 strains that captured the genetic diversity of this collection. Antibiotic susceptibility testing was also performed using 14 clinically relevant antibiotics. RESULTS: This 100-strain diversity panel contained representative strains from 91 different STs, including genetically distinct strains from major epidemic clones ST-111, ST-235, ST-244 and ST-253. Seventy-one distinct antibiotic susceptibility profiles were identified ranging from pan-susceptible to pan-resistant. Known resistance alleles as well as the most prevalent mutations underlying the antibiotic susceptibilities were characterized for all isolates. CONCLUSIONS: This panel provides a diverse and comprehensive set of P. aeruginosa strains for use in developing solutions to antibiotic resistance. The isolates and available metadata, including genome sequences, are available to industry, academia, federal and other laboratories at no additional cost.

A cluster-control approach to a coronavirus disease 2019 (COVID-19) outbreak on a stroke ward with infection control considerations for dementia and vascular units.

OBJECTIVE: We sought to contain a healthcare-associated coronavirus disease 2019 (COVID-19) outbreak, to evaluate contributory factors, and to prevent future outbreaks. DESIGN: Quasi-experimental cluster-control outbreak evaluation. METHODS: All patients and staff on the outbreak ward (case cluster), and randomly selected patients and staff on COVID-19 wards (positive control cluster) and a non-COVID-19 wards (negative control cluster) underwent reverse-transcriptase polymerase chain reaction (RT-PCR) testing. Hand hygiene and personal protective equipment (PPE) compliance, detection of environmental SARS-COV-2 RNA, patient behavior, and SARS-CoV-2 IgG antibody prevalence were assessed. RESULTS: In total, 145 staff and 26 patients were exposed, resulting in 24 secondary cases. Also, 4 of 14 (29%) staff and 7 of 10 (70%) patients were asymptomatic or presymptomatic. There was no difference in mean cycle threshold between asymptomatic or presymptomatic versus symptomatic individuals. None of 32 randomly selected staff from the control wards tested positive. Environmental RNA detection levels were higher on the COVID-19 ward than on the negative control ward (OR, 19.98; 95% CI, 2.63-906.38; P < .001). RNA levels on the COVID-19 ward (where there were no outbreaks) and the outbreak ward were similar (OR, 2.38; P = .18). Mean monthly hand hygiene compliance, based on 20,146 observations (over preceding year), was lower on the outbreak ward (P < .006). Compared to both control wards, the proportion of staff with detectable antibodies was higher on the outbreak ward (OR, 3.78; 95% CI, 1.01-14.25; P = .008). CONCLUSION: Staff seroconversion was more likely during a short-term outbreak than from sustained duty on a COVID-19 ward. Environmental contamination and PPE use were similar on the outbreak and control wards. Patient noncompliance, decreased hand hygiene, and asymptomatic or presymptomatic transmission were more frequent on the outbreak ward.

Temporal, Spatial, and Epidemiologic Relationships of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Gene Cycle Thresholds: A Pragmatic Ambi-directional Observation.

Prospective serial sampling of 70 patients revealed clinically relevant cycle thresholds (Ct) occurring 9, 26, and 36 days after symptom onset. Race, gender, and corticosteroids apparently did not influence RNA positivity. In a retrospective analysis of 180 patients, initial Ct did not correlate with requirements for admission or intensive care.

A Diverse Panel of Clinical Acinetobacter baumannii for Research and Development.

Over the past two decades, Acinetobacter baumannii has emerged as a leading cause of nosocomial infections worldwide. Of particular concern are panresistant strains, leading the World Health Organization (WHO) to designate carbapenem-resistant A. baumannii as a priority 1 (critical) pathogen for research and development of new antibiotics. A key component in supporting this effort is accessibility to diverse and clinically relevant strains for testing. Here, we describe a panel of 100 diverse A. baumannii strains for use in this endeavor. Whole-genome sequencing was performed on 3,505 A. baumannii isolates housed at the Multidrug-Resistant Organism Repository and Surveillance Network. Isolates were cultured from clinical samples at health care facilities around the world between 2001 and 2017. Core-genome multilocus sequence typing and high-resolution single nucleotide polymorphism (SNP)-based phylogenetic analyses were used to select a final panel of 100 strains that captured the genetic diversity of the collection. Comprehensive antibiotic susceptibility testing was also performed on all 100 isolates using 14 clinically relevant antibiotics. The final 100-strain diversity panel contained representative strains from 70 different traditional Pasteur scheme multilocus sequence types, including major epidemic clones. This diversity was also reflected in antibiotic susceptibility and antimicrobial resistance (AMR) gene content, with phenotypes ranging from pansensitive to panresistant, and over 100 distinct AMR gene alleles identified from 32 gene families. This panel provides the most diverse and comprehensive set of A. baumannii strains for use in developing solutions for combating antibiotic resistance. The panel and all available metadata, including genome sequences, will be available to industry and academic institutions and federal and other laboratories free of charge.

Sustainably reducing device utilization and device-related infections with DeCATHlons, device alternatives, and decision support.

Engagement of frontline staff, along with senior leadership, in competition-style healthcare-associated infection reduction efforts, combined with electronic clinical decision support tools, appeared to reduce antibiotic regimen initiations for urinary tract infections (P = .01). Mean monthly standardized infection and device utilization ratios also decreased (P < .003 and P < .0001, respectively).

Severe recurrent Streptobacillus moniliformis endocarditis in a pregnant woman, and review of the literature.

BACKGROUND: Rat bite fever is a systemic febrile illness caused by infection with the Gram-negative bacillus Streptobacillus moniliformis following a bite, scratch, or contact with excrement. Only 26 cases of native valve endocarditis have been reported to date. We could find no other reports of severe Streptobacillus endocarditis requiring valve replacement in a young, pregnant patient. CASE PRESENTATION: A pregnant patient sought care for right leg pain, fevers, left upper quadrant pain, generalized weakness, fatigue, and inability to bear weight on her right leg. She had a syncopal episode 9 months earlier, resulting in a mandibular fracture and internal fixation hardware. Her pregnancy was complicated by hyperemesis and weight loss. Her pets included a rescued wild bird, a cat, and four rats. Her parents rescued stray cats, and she recalled multiple cat bites and scratches since childhood. She denied injection drug use. Ultrasound indicated a right popliteal artery thrombus. Transesophageal echocardiogram revealed a 2 cm × 0.7 cm vegetation. Angiography demonstrated multiple splenic infarcts and bilateral renal infarcts. She underwent mitral valve repair. The mitral valve Gram stain demonstrated 2+ Gram-negative rods, rare Gram-positive rods, and moderate white blood cells. Propionibacterium spp. was isolated from the mitral valve tissue on Columbia agar incubated anaerobically. Anaerobic and aerobic cultures of the valve tissue on all other broths and agars remained negative at 14 days. Hematoxylin and eosin stains showed a fibro-inflammatory vegetation. Aggregates of rod-shaped bacteria were identified on Warthin Starry/Steiner stain. Bartonella titers were positive for B. henselae IgG 1:256, IgM < 1:20. Brown-Hopps Gram stain, AFB, and GMS stains for bacterial and fungal microorganisms were negative. Broad range bacterial PCR and sequencing of a segment of 16 s rRNA gene of the valve tissue matched to Streptobacillus sp. (genus level) and most closely related to Streptobacillus moniliformis. CONCLUSION: This case demonstrates diagnostic and therapeutic challenges associated with a relatively uncommon cause of endocarditis. The diagnosis of rat bite fever was delayed due to symptoms of a concomitant pregnancy. Other confounders included possible alternative sources or co-infections with another zoonosis from multiple pets, and an odontogenic source due to presence of exposed jaw hardware.

Case Report: A Polymicrobial Vision-Threatening Eye Infection Associated with Polysubstance Abuse.

We report a patient with risk factors for both microbial keratitis and endophthalmitis, which were initially challenging to distinguish. Cultures of corneal scrapings yielded several organisms, including an uncultivable Gram-negative rod, eventually identified as Kingella negevensis. Kingella negevensis is so named because most strains have been isolated in the Negev, a desert region of southern Israel. The epidemiology of K. negevensis remains incompletely understood. We found no other reports in the literature of this organism causing microbial keratitis.

The Rationale for a Mandatory Antibiotic Stewardship Rotation During Residency: What Worked, What Needs More Work.

Reports of antibiotic stewardship (AS) integration into the > 1000 United States internal medicine and family practice residency core curricula are scarce, but residents value such training. To help address this gap, and the projected shortage of physicians with training for establishing and leading an AS program (ASP), we describe the rationale for, and the output and shortcomings of, a dedicated AS rotation. Residents critically review, in real-time, inpatient antibiotic orders, provide feedback to the prescribers, learn the mechanics and requirements of an ASP, and complete a preliminary quality improvement project. Program evaluations are uniformly positive, noting limited opportunities otherwise to clarify optimal antibiotic choices or discuss antibiotics in depth. Nine posters at national conferences and 1 publication have roots in this rotation. Three alumni matriculated to accredited US infectious diseases fellowships. We invite others to join us in calling for more AS training opportunities during residency.