Successful Eradication of a Highly Resistant Elizabethkingia anophelis Species in a Premature Neonate With Bacteremia and Meningitis.

Elizabethkingia anophelis is a Gram-negative bacillus that can exhibit highly resistant phenotypes against most antibiotics with evidence of efficacy and safety in the neonatal population. Given the limited antimicrobial options, clinicians may be forced into challenging treatment scenarios when faced with central nervous system infections in premature neonates caused by E. anophelis . We report a case of successful treatment of hospital-acquired meningitis and bacteremia caused by E. anophelis at 11 days of life in a male infant born at 29 weeks, 1 day gestation and birth weight of 1.41 kg. Therapy consisted of vancomycin, dose adjusted to maintain goal troughs of 15-20 mg/L, and rifampin 10 mg/kg/dose every 12 hours, with ciprofloxacin 15 mg/kg/dose every 12 hours and trimethoprim/sulfamethoxazole 5 mg/kg/dose every 12 hours added due to antimicrobial susceptibilities and unsatisfactory response, for a total of 21 days. Following initiation of this multidrug regimen, repeat cultures were negative, laboratory parameters improved [with exception of elevated cerebrospinal fluid (CSF) white blood cell count], the patient remained otherwise stable, and there were no adverse effects noted from therapy. Complications after treatment included the requirement of bilateral hearing aids and the development of hydrocephalus necessitating ventriculoperitoneal shunt placement. To our knowledge, we report the first case of meningitis in a premature neonate initially identified as E. anophelis in the United States treated with this regimen which led to successful microbiologic eradication with no antimicrobial safety concerns.

The hidden microbiome of hospital infection surveillance testing: biomarkers of health outcomes in MRSA and VRE colonization.

Background: Hospital-acquired infections present a major concern for healthcare systems in the U.S. and worldwide. Drug-resistant infections result in increased costs and prolonged hospital stays. Methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) are responsible for many drug-resistant infections in the U.S. We undertook two parallel studies aimed to investigate the differences in the microbial communities of individuals colonized with MRSA (or VRE) as compared to their respective non-colonized counterparts matched for age, sex, race, ethnicity, unit of admission, and diagnostic-related group, when available. Results: The VRE study showed considerably more Enterococcus genus communities in the VRE colonized samples. Our findings for both MRSA and VRE studies suggest a strong association between 16S rRNA gene alpha diversity, beta diversity, and colonization status. When we assessed the colonized microbial communities in isolation, the differences disappeared, suggesting that the colonized microbial communities drove the change. Isolating Staphylococcus, we saw significant differences expressed across colonization in specific sequence variants. Conclusions: The differences seen in the microbial communities from MRSA (or VRE) colonized samples as compared to non-colonized match-pairs are driven by the isolated communities of the Staphylococcus (or Enterococcus) genus, the removal of which results in the disappearance of any differences in the diversity observed across the match-pairs.

Inhaled nitric oxide for adults with pulmonary non-tuberculous mycobacterial infection.

QUESTION: There is an increasing prevalence of nontuberculous mycobacteria pulmonary disease (NTM-PD) in the US. Treatment of NTM-PD typically requires multiple medications, which can be associated with unpleasant morbidity and eradication of infection is difficult. Therefore, there is a critical need for novel effective and well-tolerated therapies. Recent in vitro data and case reports have suggested that nitric oxide, inhaled as a gas (gNO), has antimicrobial activity against NTM. We sought to investigate the effect of gNO in patients with NTM-PD in an open-label proof of concept trial. METHODS: Eligible participants had NTM-PD with persistently positive respiratory cultures for NTM even if on antibiotic treatment. Participants were treated with gNO for 50 min three times daily, five days per week, for three weeks (total of 15 treatment days). RESULTS: Ten participants, of whom nine were on long-term NTM antibiotic therapy, were enrolled. All participants completed the regimen without interruption or discontinuation. Small increases in methemoglobin were noted during treatment, and all resolved to baseline within 2 h. Four participants (40%) met the primary outcome measure of negative sputum cultures after three weeks of therapy. Following treatment discontinuation, three of these participants were again culture positive during the 3-month post-treatment monitoring period, although with measures suggesting low bacterial burden. ANSWER: Patients tolerated a 3-week regimen of gNO without safety concerns, and despite highly refractory disease four individuals completed the study with negative cultures, although three were again positive in subsequent months. These data support further investigation of gNO as a potential therapy for NTM-PD.

Identification of the main contributors to blood culture contamination at a tertiary care academic medical center.

Background: Blood culture contamination poses an issue to all hospital systems worldwide because of the associated costs of extended length of stays, unnecessary antibiotic therapy, and additional laboratory testing that are preventable with proper handling and collection techniques. Methods: In our study, multiple units, staff, and collection methods were compared to determine the primary culprits of contamination from a tertiary care academic medical center, which includes a pediatric hospital and both adult and pediatric emergency departments. Results: Over 33 months, 2,083 out of 88,322 total blood cultures collected were contaminated, with an overall contamination rate of 2.4%. A moderate positive correlation was found between the monthly total number of cultures and monthly contamination rate (r = 0.411 P < .01). The most notable factors associated with contamination were found to be phlebotomy teams (2.7%) (P < .01), peripheral draws (2.3%) (P <.01), adult emergency departments (2.6%) (P < .01), and pediatric intensive care units (2.7%) (P < .01). A positive correlation was present between the number of hospital beds per unit and unit contamination rates (r = 0.429 P < .01). Conclusion: Our results were used to make recommendations for decreasing the rate of blood culture contamination in this institution, which includes acknowledgement of an overwhelmed staff and mandatory periodic training on acceptable aseptic technique and contamination awareness. Understanding the factors contributing to blood culture contamination can aid efforts to reduce contamination rates.

Effects of COVID-19 on Blood Culture Contamination at a Tertiary Care Academic Medical Center.

The COVID-19 pandemic has changed health care, from increased needs of personal protective equipment (PPE) to overloaded staff and influxes of patients. Blood cultures are frequently used to detect bloodstream infections in critically ill patients, but it is unknown whether the COVID-19 pandemic has had an impact on blood culture contamination rates. A total of 88,332 blood cultures taken over a 33-month period were analyzed to compare blood culture contamination rates before the COVID-19 pandemic to rates during the pandemic. A significant increase in the average number of monthly nurse-drawn and peripherally collected cultures occurred after the start of the pandemic, but there was a decrease in the average number of phlebotomy cultures. A significant increase in contamination rates (P < 0.001) was found in all nonemergency hospital departments during the COVID-19 pandemic, increasing from 2.1% to 2.5%. Increased rates during the COVID-19 pandemic were also found for nursing staff (2.0% to 2.4%) and both peripheral (2.1% to 2.5%) and indwelling line draws (1.1% to 1.7). The number of cultures drawn monthly increased in acute adult departments and both adult and pediatric emergency departments. Blood culture contamination rates in adult acute, adult emergency, and pediatric intensive care units increased after the start of the pandemic by 23%, 75%, and 59%, respectively. A positive correlation was found between blood culture contamination rates and COVID-19 incidence rates. Additional periodic staff training on proper blood collection technique and awareness of the workload of health care workers are recommended to decrease contamination rates during the COVID-19 pandemic. IMPORTANCE Understanding factors that contribute to blood culture contamination is important in order to take steps to limit contamination events. Here, we examine the effect the COVID-19 pandemic has had on blood culture contamination rates and specifically detail the effects based on the staff, draw types, and unit types. The conclusions provided here can be used as hospitals and laboratories navigate the COVID-19 pandemic or other times of high patient volume.

Increasing Recognition of Community-Acquired, Non-Tuberculous Mycobacterial Infections of the Hand and Wrist.

Background In this study, we present our experience with community-acquired, culture-positive, non-tuberculous mycobacterial (NTM) infections of the hand and wrist and compare the clinical features, risk factors, diagnostic delays, and treatment outcomes among patients referred for surgical consultation at our institution over a five-year period. Methodology We retrospectively identified patients on chart review who were diagnosed with culture-positive, extrapulmonary, cutaneous NTM infections between January 1, 2014, and December 31, 2018. Only patients with community-acquired NTM infections of the hand and wrist were included. Patient demographics, risk factors, location, diagnostic delays, NTM species isolated, treatment modalities, and treatment outcomes were collected and analyzed. These variables were further compared between patients who participated in fishing-related activities and those who did not. Results A total of 10 patients were identified with community-acquired NTM infections of the hand or wrist. Of these patients, eight (80%) were male, and six (60%) had participated in fishing-related activities prior to the initial presentation. The majority of patients had Mycobacterium marinum isolates (n = 6, 60%) and involved the hand (n = 8, 80%). M. marinum isolates were associated with a significantly shorter time to diagnosis (p = 0.02). All patients underwent surgical management with a prolonged course of postoperative antibiotics and were cured of their infection at the end of their treatment course. Conclusions Proper risk factor documentation and heightened clinical awareness are essential to reduce delays in the diagnosis of NTM skin and soft tissue infections and provide the best chance for curative therapy.

First reported case of disseminated Microascus gracilis infection in a lung transplant patient.

Microascus gracilis is a specie of the genus Microascus in the family of Microascaceae and has been isolated from lung. It has never been reported as the cause of disseminated infection in humans. Herein, we report a fatal case of disseminated Microascus gracilis infection in a 65-year-old man with a history of primary idiopathic pulmonary fibrosis, status-post bilateral lung transplant. His course was complicated by donor lung cultures positive for multiple organisms and persistent pleural effusions. Multiple lung biopsy and bronchial lavage specimens were negative for mold. Later, pleural fluid cultures grew M. gracilis confirmed by DNA sequencing. Despite aggressive antifungal treatment, the patient continued to deteriorate with altered mental status. Imaging showed scattered hemorrhagic and hypodense lesions in the brain. The patient eventually succumbed to his infections and a restricted autopsy was performed. Autopsy findings included multiple hemorrhagic foci and abscesses involving the whole brain. Numerous punctuate, tan-white circular lesions were on the endocardium and diffuse tan exudates covered the pericardium and lungs. Histologically, similar fungal organisms with septate branching hyphae and short chains of conidia were identified, along with hemorrhage, neutrophilic inflammation, and necrosis in the brain, pleura, peripheral parenchyma of lungs and heart. This is the first reported case of disseminated M. gracilis infection in an immunosuppressed human, indicating it can cause localized infections and disseminated infections. This case increases our awareness of such fatal opportunistic infections, particularly in lung transplant patients, and urges earlier aggressive prophylaxis, diagnosis, and treatment.

Risk Factors for Fungal Prosthetic Joint Infection.

Background: Fungal prosthetic joint infections (PJIs) are rare and often associated with poor outcome; however, risk factors are not well described. Methods: This was a retrospective case control study among all patients with PJIs from 2006-2016 at two major academic centers. Each fungal PJI case was matched 1:1 with a bacterial PJI control by joint (hip, knee, shoulder) and year of diagnosis. We compared demographics, comorbidities, and clinical characteristics between cases and controls using chi square/Fisher's exact or Wilcoxon rank sum test. Independent risk factors were identified with multivariable logistic regression. Results: Forty-one fungal PJIs occurred over the study and 61% were due to Candida albicans. The hip was involved in 51.2% of cases, followed by the knee (46.3%). Compared to bacterial PJI, fungal PJI cases were more likely to have received antibiotics within the previous 3 months (70.7% vs 34%, P=.001), wound drainage lasting >5 days (48% vs 9%, P=.0002), had a lower median CRP (2.95 mg/dl vs 5.99, P=.013) and synovial fluid white blood cell count (13,953 cells/mm3 vs 33,198, P=.007), and a higher proportion of prior two-stage exchanges (82.9% vs 53.6%, P=.008). After controlling for center, prolonged wound drainage (OR, 7.3; 95% CI, 2.02-26.95) and recent antibiotics (OR, 3.4; 95% CI, 1.2-9.3) were significantly associated with fungal PJI. Conclusion: In our study, Candida albicans was the most common species in fungal PJIs and prolonged wound drainage and recent antibiotics were independent risk factors. These clinical characteristics may help providers anticipate fungal PJI and adjust management strategies.

Multicenter Evaluation of a PCR-Based Digital Microfluidics and Electrochemical Detection System for the Rapid Identification of 15 Fungal Pathogens Directly from Positive Blood Cultures.

Routine identification of fungal pathogens from positive blood cultures by culture-based methods can be time-consuming, delaying treatment with appropriate antifungal agents. The GenMark Dx ePlex investigational use only blood culture identification fungal pathogen panel (BCID-FP) rapidly detects 15 fungal targets simultaneously in blood culture samples positive for fungi by Gram staining. We aimed to determine the performance of the BCID-FP in a multicenter clinical study. Blood culture samples collected at 10 United States sites and tested with BCID-FP at 4 sites were compared to the standard-of-care microbiological and biochemical techniques, fluorescence in situ hybridization using peptide nucleic acid probes (PNA-FISH) and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). Discrepant results were analyzed by bi-directional PCR/sequencing of residual blood culture samples. A total of 866 clinical samples, 120 retrospectively and 21 prospectively collected, along with 725 contrived samples were evaluated. Sensitivity and specificity of detection of Candida species (C. albicans, C. auris, C. dubliniensis, C. famata, C. glabrata, C. guilliermondii, C. kefyr, C. krusei, C. lusitaniae, C. parapsilosis, and C. tropicalis) ranged from 97.1 to 100% and 99.8 to 100%, respectively. For the other organism targets, sensitivity and specificity were as follows: 100% each for Cryptococcus neoformans and C. gattii, 98.6% and 100% for Fusarium spp., and 96.2% and 99.9% for Rhodotorula spp., respectively. In 4 of the 141 clinical samples, the BCID-FP panel correctly identified an additional Candida species, undetected by standard-of-care methods. The BCID-FP panel offers a faster turnaround time for identification of fungal pathogens in positive blood cultures that may allow for earlier antifungal interventions and includes C. auris, a highly multidrug-resistant fungus.

Cutibacterium acnes Infection in Orthopedics: Microbiology, Clinical Findings, Diagnostic Strategies, and Management.

Cutibacterium (formerly called Propionibacterium) acnes is a human skin flora often implicated in orthopedic infections. The unique characteristics of this microorganism make the diagnosis of infection difficult. The diagnosis often is made based on clinical evidence, radiographic signs, and laboratory and/or surgical findings combined. Treatment often involves both pharmacologic and surgical methods. In addition, formation of biofilms and increased resistance to drugs exhibited by the microorganism can require combined antimicrobial therapy. Prophylactic measures are particularly important, but no single method has been shown to fully eliminate the risk of C acnes infections. Previous reports have focused on C acnes infections involving surgical implants or after certain orthopedic procedures, particularly in the shoulder and spine. This article reviews current clinical, diagnostic, and treatment principles for C acnes in orthopedics in general. [Orthopedics. 2020; 43(1):52-61.].

National and regional modeling of distinct RSV seasonality thresholds for antigen and PCR testing in the United States.

BACKGROUND: PCR tests now outnumber antigen tests for the diagnosis of respiratory syncytial virus (RSV) infection in the US. Recent analyses have shown that the traditional 10% positivity threshold to define an RSV season by rapid antigen testing was inappropriate for real-time PCR testing, for which 3% positivity appeared more appropriate. OBJECTIVE: To respectively model antigen (10%) and PCR (3%) positivity thresholds at national and regional levels using a large dataset of RSV testing results from US hospital-affiliated laboratories. STUDY DESIGN: From 2011-2016, 599 laboratories participated in a national RSV surveillance program (RSVAlert®). For laboratories with ≥10 tests for ≥30 weeks of a season, national and regional test numbers and positivity were summarized by test type overall, by season, and weekly within each season. Test type positivity thresholds were used to calculate season onset and offset. RESULTS: A seasonal average of 543,387 RSV tests was reported. PCR testing increased from 26% in 2011-2012 to 72% in 2015-2016. Overall, national positivity was 15.6% for antigen and 8.3% for PCR testing. National RSV season onsets and offsets were comparable using the 10% antigen and 3% PCR thresholds, but PCR-defined seasons generally started and ended later than antigen-defined seasons. Regionally, there were fewer outlier estimates of RSV season length when the predominant regional test type was used to define the season. CONCLUSION: RSV positivity rates differed by test type, likely due to differential clinical use of the tests. These findings support the use of distinct positivity thresholds by test type.

A Case of Malaria Predisposing to Salmonella Bacteremia in a Returning Traveler from Nigeria.

We describe a febrile adult returning to the U.S. from Nigeria. Malaria was diagnosed by rapid antigen testing, but recognition of invasive nontyphoidal Salmonella disease was delayed. While the moniker, "typhomalaria," once used to describe an illness with features of malaria and typhoid fever, has fallen out of favor, it may nevertheless be a helpful reminder to clinicians that both infectious diseases can arise in the same patient. Blood cultures should be obtained routinely in febrile returning travelers from malaria-endemic regions, including those in whom the diagnosis of malaria has already been established.

In Vitro Activity of Ceftolozane/Tazobactam vs Nonfermenting, Gram-Negative Cystic Fibrosis Isolates.

Ceftolozane/tazobactam (C/T) was tested and compared against 93 nonfermenting, Gram-negative clinical isolates from cystic fibrosis specimens. Based on current breakpoints for intra-abdominal and urinary tract infections (which may not be appropriate for pulmonary infections), C/T was found to be the most active agent against P. aeruginosa (95.7% susceptible), followed by piperacillin/tazobactam (89.4% susceptible). For other Gram-negative pathogens included, C/T had varying activity.

Emergence of Ceftolozane-Tazobactam-Resistant Pseudomonas aeruginosa during Treatment Is Mediated by a Single AmpC Structural Mutation.

Ceftolozane-tazobactam is a cephalosporin-ß-lactamase inhibitor combination that exhibits potent in vitro activity against Pseudomonas aeruginosa, including strains that are resistant to other ß-lactams. The emergence of ceftolozane-tazobactam resistance among clinical isolates of P. aeruginosa has rarely been described. Here we characterized ceftolozane-tazobactam-resistant P. aeruginosa strains recovered from a patient who was treated with this agent for 6 weeks for a recurrent wound infection. The results showed that the resistance was mediated by a single AmpC structural mutation.

The Role of Antimicrobial Stewardship in the Clinical Microbiology Laboratory: Stepping Up to the Plate.

We report the development of a collaborative relationship between antimicrobial stewardship and clinical microbiology that incorporates stewardship practices into daily laboratory rounds. Antimicrobial stewardship involvement on rounds was a welcomed and effective initiative with substantial rates of intervention. New opportunities to positively impact use of antimicrobials and laboratory resources were realized.

Actinomyces meyeri, a Common Agent of Actinomycosis.

BACKGROUND: Actinomyces, particularly Actinomyces israelii, may cause indolent, persistent infections or represent normal mucosal flora, leading to management dilemmas. MATERIALS AND METHODS: Prompted by a refractory Actinomyces meyeri infection complicating AIDS, clinical data for all Actinomyces isolates at our hospital laboratory since 1998 were analyzed. RESULTS: A total of 140 cases had a positive result for Actinomyces cultures. Of 130 cases with adequate follow-up, 36 (28%) cases had end-organ or disseminated disease treated with prolonged antibiotics or surgery or both (Group 1). A. meyeri was more common than A. israelii (33% versus 8%; P < 0.05) in Group 1, particularly thoracic infections. Another 56 (43%) cases were considered local pathogens, treated with drainage only or short-course antibiotics (Group 2). Another 38 (29%) cases were deemed commensals (Group 3). Immunosuppression was less frequent in Group 1 versus Group 2 or 3 (P = 0.05) and human immunodeficiency virus or AIDS was uncommon. Foreign bodies or devices (Group 1 versus Group 2 or 3, P = 0.003) and alcoholism (Group 1 versus Group 2 or 3; P = 0.03) were associated with actinomycosis. Isolates from the central nervous system and musculoskeletal sites were more often treated as definitive disease; skin, abdominal or pelvic or single blood culture isolates were more likely commensals (all P < 0.05). Disease progression or recurrence did not occur in Groups 2 and 3, whereas Group 1 had complex and variable courses, including 2 deaths. CONCLUSIONS: In the absence of disseminated or end-organ disease, avoiding prolonged therapy for Actinomyces isolates was not associated with adverse outcomes. Alcoholism or foreign bodies were associated with actinomycosis. A. meyeri may be a more common cause of actinomycosis than previously recognized.

Epidemiology of Rapidly Growing Mycobacteria Bloodstream Infections.

BACKGROUND: Rapidly growing mycobacteria (RGM) bloodstream infections (BSI) are an emerging problem often associated with therapeutic challenges. We review the epidemiology, treatment and outcomes over a 5-year period of a heterogeneous group presenting to our institution with RGM BSI. MATERIALS AND METHODS: A retrospective cohort study of patients with primary RGM BSI from January 2006-December 2011 was conducted. Patient characteristics (age, race, sex and comorbidities), infection characteristics (catheter associated, hospital acquired, microbiology and antimicrobial susceptibilities), therapy and outcomes were recorded and compared by species. RESULTS: Among 32 patients, 33 RGM BSI occurred. Patients had an average of 3-4 comorbidities, most commonly malignancy (45.5%). Most isolates (30.3%) were Mycobacterium fortuitum or Mycobacterium mucogenicum (27.2%), followed by Mycobacterium abscessus/chelonae (18.2%) and Mycobacterium immunogenum (12.2%). In all, 85% were catheter associated and 27.3% were hospital acquired. Empiric therapy was started in 19 (57.6%) patients and among these, it was adequate (at least 2 active agents based on susceptibilities) in 12 (63.2%). Among 21 patients with outcome data, cure was assumed for 14 (66.7%). One death was attributable to RGM BSI. Cure rates were higher among those who received adequate empiric therapy compared to those who did not (83.3% versus 42.9%). In general, antibiotic susceptibility was favorable across species for clarithromycin, amikacin and imipenem. CONCLUSIONS: RGM BSI occurred in a population with multiple comorbidities, most commonly malignancy, and most were catheter associated. Higher cures were seen among those who received adequate empiric therapy and based on susceptibility data, a broad empiric regimen of clarithromycin, amikacin and imipenem would be expected to be adequate.

Clinical Features and Outcomes of Pasteurella multocida Infection.

Pasteurella multocida, a zoonotic infectious organism, has most often been described in patients after an animal bite. Here, we characterize the clinical features and outcomes of P multocida infection in a large cohort of patients according to the presence or absence of an animal bite.We retrospectively searched MUSC's laboratory information system for all patients with positive P multocida cultures from 2000 to 2014. Extensive data were abstracted, including clinical and outcome data. The Charlson comorbidity index (CCI) was used to assess comorbidities among patients.We identified 44 patients with P multocida infections, including 25 with an animal bite. The average age was 64 years and the majority of patients were women (N = 30). There was no difference in age and sex distribution among those with and without a bite (P = 0.38 and 0.75, respectively). A CCI ≥1 was significantly associated with the absence of a bite (P = 0.006). Patients presenting without a bite were more frequently bacteremic (37% vs 4%, respectively, P = 0.001), and were hospitalized more often (84% vs 44%, respectively, P = 0.012). Of the 8 patients who required intensive care unit (ICU)-based care, 7 were non-bite-related. There were 4 deaths, all occurring in patients not bitten.P multocida infections not associated with an animal bite were often associated with bacteremia, severe comorbidity(ies), immune-incompetent states, the need for ICU management, and were associated with substantial mortality.