Travel Surveillance and Genomics Uncover a Hidden Zika Outbreak during the Waning Epidemic.

The Zika epidemic in the Americas has challenged surveillance and control. As the epidemic appears to be waning, it is unclear whether transmission is still ongoing, which is exacerbated by discrepancies in reporting. To uncover locations with lingering outbreaks, we investigated travel-associated Zika cases to identify transmission not captured by reporting. We uncovered an unreported outbreak in Cuba during 2017, a year after peak transmission in neighboring islands. By sequencing Zika virus, we show that the establishment of the virus was delayed by a year and that the ensuing outbreak was sparked by long-lived lineages of Zika virus from other Caribbean islands. Our data suggest that, although mosquito control in Cuba may initially have been effective at mitigating Zika virus transmission, such measures need to be maintained to be effective. Our study highlights how Zika virus may still be "silently" spreading and provides a framework for understanding outbreak dynamics. VIDEO ABSTRACT.

Genomic epidemiology reveals multiple introductions of Zika virus into the United States.

Zika virus (ZIKV) is causing an unprecedented epidemic linked to severe congenital abnormalities. In July 2016, mosquito-borne ZIKV transmission was reported in the continental United States; since then, hundreds of locally acquired infections have been reported in Florida. To gain insights into the timing, source, and likely route(s) of ZIKV introduction, we tracked the virus from its first detection in Florida by sequencing ZIKV genomes from infected patients and Aedes aegypti mosquitoes. We show that at least 4 introductions, but potentially as many as 40, contributed to the outbreak in Florida and that local transmission is likely to have started in the spring of 2016-several months before its initial detection. By analysing surveillance and genetic data, we show that ZIKV moved among transmission zones in Miami. Our analyses show that most introductions were linked to the Caribbean, a finding corroborated by the high incidence rates and traffic volumes from the region into the Miami area. Our study provides an understanding of how ZIKV initiates transmission in new regions.

Multicenter Evaluation of Ceftolozane/Tazobactam for Serious Infections Caused by Carbapenem-Resistant Pseudomonas aeruginosa.

A multicenter, retrospective study of patients infected with carbapenem-resistant Pseudomonas aeruginosa who were treated with ceftolozane/tazobactam was performed. Among 35 patients, pneumonia was the most common indication and treatment was successful in 26 (74%). Treatment failure was observed in all cases where isolates demonstrated ceftolozane-tazobactam minimum inhibitory concentrations ≥8 µg/mL.

The Prevalence of Atrial Fibrillation and Conduction Abnormalities in Chagas' Disease: A Meta-Analysis.

BACKGROUND/OBJECTIVES: Chagas' disease (CD) has been associated with atrial fibrillation (AF) and electrocardiographic (ECG) conduction defects. However, prior studies have shown conflicting results. We performed a meta-analysis comparing the prevalence of AF and conduction abnormalities between CD and non-CD patients. METHODS: PubMed, EMBASE, Cochrane Central, and Latin American databases were searched for studies that directly compared the prevalence of AF and conduction defects in CD and non-CD patients. Odds ratios (OR) were computed using random-effects model due to anticipated heterogeneity. We further performed subanalyses limited to studies that included only patients with cardiomyopathy. RESULTS: A total of 17,238 patients from 30 studies were included, of whom 6,840 (40%) had a positive serology for CD. In the pooled data, AF was significantly more prevalent in the CD group (OR 1.62; 95%CI 1.21-2.15; P = 0.001). However, no significant difference was observed between groups when the analysis included only patients with cardiomyopathy (OR 1.21; 95%CI 0.97-1.50; P = 0.08) or heart failure (OR 1.09; 95%CI 0.81-1.47; P = 0.55). The combination of right bundle branch block (RBBB) and left anterior fascicular block (LAFB) had the highest OR for increased prevalence in patients with Chagas' cardiomyopathy compared to non-CD etiologies (OR 5.31; 95%CI 1.23-22.86; P = 0.03). CONCLUSIONS: Our meta-analysis suggests that the prevalence of AF in patients with Chagas' cardiomyopathy is not significantly different from non-CD cardiomyopathies. The pattern of RBBB and LAFB in patients with cardiomyopathy of unknown etiology and epidemiologic risk factors should raise the possibility of CD and prompt specific diagnostic testing.

Knowledge, attitudes, and practices of Florida physicians regarding dengue before and after an educational intervention.

BACKGROUND: Failure to recognize and appropriately manage dengue early in the clinical course may result in late initiation of supportive treatment for severe disease. In Florida, travel-related and autochthonous dengue occur and are likely under-recognized. The objective of this study was to evaluate physician knowledge of dengue and its management before and after an educational intervention in Florida. METHODS: From 2012-13 we conducted 14 grand-rounds style lectures on dengue clinical management attended by 413 physicians, and analyzed data from the pre- and post-tests. RESULTS: Of those attending, 231 and 220 completed the pre-and post-tests, respectively. Overall, the mean pre-test score for knowledge-based questions was 74.3 and average post-test score was 94.2%, indicating a mean increase of 19.9% (P < 0.0001, 95% CI 17.7-22.4). Reported confidence in dengue recognition and management also increased. Non-US trained physicians and those who had treated more than ten dengue cases performed significantly better in the pre-test. Post-test scores did not differ by subgroup. CONCLUSIONS: The train-the-trainer approach with grand-rounds style presentations appear to be an effective intervention to improve knowledge of dengue among physicians.

Proactive risk stratification and low-risk penicillin allergy delabeling by an antimicrobial stewardship pharmacist.

Penicillin (PCN) allergy delabeling is an important component of antimicrobial stewardship; however, widespread implementation has lagged. We found that most patients had low-risk PCN allergy histories eligible for delabeling without skin testing. Pharmacist-led risk stratification and drug challenge expanded access to delabeling independently from an Allergy/Immunology service.

Clostridium difficile Bacteremia as a Rare Presentation of Polymicrobial Pyogenic Liver Abscesses and Its Management Challenges.

Extracolonic manifestations of Clostridium difficile have been rarely reported. We herein report a case of a 60-year-old immunocompetent man presenting with fever, nausea, abdominal pain, and loose stools for 2 weeks. Triple-phase liver computed tomography demonstrated pyogenic liver abscesses and portal pylephlebitis. Blood cultures grew C. difficile and Bacteroides fragilis, and liver abscess cultures grew Proteus mirabilis, Escherichia coli, and the viridans group Streptococci. Antibiotics coverage was selected to direct at all identified organisms. This demonstrates an unusual case of C. difficile bacteremia in a patient with polymicrobial pyogenic liver abscesses and pylephlebitis.

Antimicrobial Consumption from 2017 to 2021 in East Trinidad and Tobago: A Study in the English-Speaking Caribbean.

An antimicrobial consumption (AMC) study was performed in Trinidad and Tobago at the Eastern Regional Health Authority (ERHA). A retrospective, cross-sectional survey was conducted from 1 November 2021 to 30 March 2022. Dosage and package types of amoxicillin, azithromycin, co-amoxiclav, cefuroxime, ciprofloxacin, levofloxacin, moxifloxacin, nitrofurantoin and co-trimoxazole were investigated. Consumption was measured using the World Health Organization's Antimicrobial Resistance and Consumption Surveillance System methodology version 1.0, as defined daily doses (DDD) per 1000 population per day (DID). They were also analyzed using the 'Access', 'Watch' and 'Reserve' classifications. In the ERHA, AMC ranged from 6.9 DID to 4.6 DID. With regards to intravenous formulations, the 'Watch' group displayed increased consumption, from 0.160 DID in 2017 to 0.238 DID in 2019, followed by a subsequent drop in consumption with the onset of the COVID-19 pandemic. Oral co-amoxiclav, oral cefuroxime, oral azithromycin and oral co-trimoxazole were the most highly consumed antibiotics. The hospital started off as the higher consumer of antibiotics, but this changed to the community. The consumption of 'Watch' group antibiotics increased from 2017 to 2021, with a drop in consumption of 'Access' antibiotics and at the onset of COVID-19. Consumption of oral azithromycin was higher in 2021 than 2020.

Successful Outcome after Treatment with Cidofovir, Vaccinia, and Extended Course of Tecovirimat in a Newly-Diagnosed HIV Patient with Severe Mpox: A Case Report.

PURPOSE: To report a case of severe mpox in a newly diagnosed HIV patient concerning for Immune Reconstitution Inflammatory Syndrome (IRIS) and/or tecovirimat resistance and to describe the management approach in the setting of refractory disease. CASE: 49-year-old man presented with 2 weeks of perianal lesions. He tested positive for mpox PCR in the emergency room and was discharged home with quarantine instructions. Three weeks later, the patient returned with disseminated firm, nodular lesions in the face, neck, scalp, mouth, chest, back, legs, arms, and rectum, with worsening pain and purulent drainage from the rectum. The patient reported being on 3 days of tecovirimat treatment, which was prescribed by the Florida department of health (DOH). During this admission, he was found to be HIV positive. A pelvic CT scan revealed a 2.5 cm perirectal abscess. Treatment with tecovirimat was continued for 14 days, along with an empiric course of antibiotics for treatment of possible superimposed bacterial infection upon discharge. He was seen in the outpatient clinic and initiated antiretroviral therapy (ART) with TAF/emtricitabine/bictegravir. Two weeks after starting ART, the patient was readmitted for worsening mpox rash and rectal pain. Urine PCR also returned positive for chlamydia, for which the patient was prescribed doxycycline. He was discharged on a second course of tecovirimat and antibiotic therapy. Ten days later, the patient was readmitted for the second time due to worsening symptoms and blockage of the nasal airway from progressing lesions. At this point, there were concerns for tecovirimat resistance, and after discussion with CDC, tecovirimat was reinitiated for the third time, with the addition of Cidofovir and Vaccinia, and showed an improvement in his symptoms. He received three doses of cidofovir and two doses of Vaccinia, and the patient was then discharged to complete 30 days of tecovirimat. Outpatient follow-up showed favorable outcomes and near resolution. CONCLUSION: We reported a challenging case of worsening mpox after Tecovirimat treatment in the setting of new HIV and ART initiation concerning IRIS vs. Tecovirimat resistance. Clinicians should consider the risk of IRIS and weigh the pros and cons of initiating or delaying ART. In patients not responding to first-line treatment with tecovirimat, resistance testing should be performed, and alternative options should be considered. Future research is needed to establish guidance on the role of Cidofovir and Vaccinia immune globulin and the continuation of tecovirimat for refractory mpox.

Timely explantation of tobramycin-impregnated beads and bone cement to avoid haemodialysis in a patient with worsening renal failure.

A male patient with right total knee arthroplasty complicated by prosthetic joint infection on intravenous antimicrobials developed an acute kidney injury (AKI) with creatinine up to 7.3 mg/dL ('normal' range (0.5-1.2 mg/dL)) after hardware removal and tobramycin loaded polymethylmethacrylate beads and spacer placement. The AKI was initially attributed to intravenous vancomycin. Despite discontinuing vancomycin, the AKI worsened. A tobramycin level was collected and resulted at 5.5 µg/mL. Due to high suspicion for aminoglycoside-induced renal toxicity and to prevent haemodialysis, the antibiotic cement spacer with tobramycin-impregnated beads was removed. After the removal, tobramycin level rapidly decreased and renal functions improved. AKI is an increasingly recognised complication related to antibiotic-loaded bone cement (ALBC) due to the systemic absorption of antibiotics. With this case we highlight the early recognition of ALBC-induced renal toxicity necessitating explantation of ALBC and beads in order to prevent haemodialysis and emphasise monitoring aminoglycoside levels in the early postoperative period.

Clinical presentation of Monkeypox among people living with HIV in South Florida: a case series.

Introduction: Monkeypox, historically a zoonotic disease caused by monkeypox virus, is a new global health emergency. Since May 2022, dozens of non-endemic countries have seen new cases with rapid spread. Generally a self-limited disease, there are vulnerable populations, in which severe or deadly illness can occur. There is limited data on immunocompromised patients in this outbreak, particularly on people living with HIV, who are disproportionately affected. Methods: We reported seven cases of monkeypox in people living with HIV in South Florida, USA. Relevant demographic, epidemiologic and clinical data were described. Results: All the patients were men, identified as gay or bisexual, and were on combination antiretroviral therapy (cART) for HIV. Six of the seven had CD4 counts more than 200 cells/mm3 (one unknown level), and one of the seven had detectable HIV viral load. Six had sexual or intimate contact with asymptomatic partners prior to development of symptoms. Two were hospitalized, one for proctitis and one for an increasing number of lesions. Six had disseminated lesions and one had localized perianal lesions and all had 5-25 total number of lesions. Five received tecovirimat with resolution of lesions in 2-14 days and all were doing well at the time of the present report. Close contacts received the Jynneos vaccine which was well tolerated. Conclusions: Our case series described monkeypox in people living with HIV and have noted atypical symptoms (lack of fever and more notable anogenital lesions) and relatively mild course as described in HIV seronegative patients. We stress the importance of early detection and isolation as well as vaccination to contacts, which has been well tolerated. In our case series, we are unable to estimate the effectiveness of tecovirimat given the limited number of patients, but all our patients had lesions that resolved within two weeks of rash onset and had no side effects reported.

Identification of novel factors associated with inappropriate treatment of asymptomatic bacteriuria in acute and long-term care.

BACKGROUND: Chart reviews often fall short of determining what drove antibiotic treatment of asymptomatic bacteriuria (ASB). To overcome this shortcoming, we searched providers' free-text for documentation of their decision-making and for misleading signs and symptoms that may trigger unnecessary treatment of ASB. METHODS: We reviewed a random sample of 10 positive urine cultures per month, per facility, from patients in acute or long-term care wards at 8 Veterans Affairs facilities. Cultures were classified as urinary tract infection (UTI) or ASB, and as treated or untreated. Charts were searched for 13 potentially misleading symptoms, and free-text documentation of providers' decision-making was classified into 5 categories. We used generalized estimating equations logistic regression to identify factors associated with ASB treatment. RESULTS: One hundred fifty-eight (27.5%) of 575 ASB cases were inappropriately treated with antibiotics. Significant factors associated with inappropriate treatment included: abdominal pain, falls, decreased urine output, urine characteristics, abnormal vital signs, laboratory values, and voiding issues. Providers prescribed an average of 1.4 antimicrobials to patients with ASB, with cephalosporins (41%) and fluoroquinolones (21%) being the most common classes prescribed. CONCLUSIONS: Chart reviews of providers' decision-making highlighted new factors associated with inappropriate ASB treatment. These findings can help design antibiotic stewardship interventions for ASB.

Analysis of an Antibiotic Stewardship Program for Asymptomatic Bacteriuria in the Veterans Affairs Health Care System.

Importance: Antibiotic stewardship for asymptomatic bacteriuria (ASB) is an important quality improvement target. Understanding how to implement successful antibiotic stewardship interventions is limited. Objective: To evaluate the effectiveness of a quality improvement stewardship intervention on reducing unnecessary urine cultures and antibiotic use in patients with ASB. Design, Setting, and Participants: This interrupted time series quality improvement study was performed at the acute inpatient medical and long-term care units of 4 intervention sites and 4 comparison sites in the Veterans Affairs (VA) health care system from October 1, 2017, through April 30, 2020. Participants included the clinicians who order or collect urine cultures and who order, dispense, or administer antibiotics. Clinical outcomes were measured in all patients in a study unit during the study period. Data were analyzed from July 6, 2020, to May 24, 2021. Intervention: Case-based teaching on how to apply an evidence-based algorithm to distinguish urinary tract infection and ASB. The intervention was implemented through external facilitation by a centralized coordinating center, with a site champion at each intervention site serving as an internal facilitator. Main Outcomes and Measures: Urine culture orders and days of antibiotic therapy (DOT) and length of antibiotic therapy in days (LOT) associated with urine cultures, standardized by 1000 bed-days, were obtained from the VA's Corporate Data Warehouse. Results: Of 11 299 patients included, 10 703 (94.7%) were men, with a mean (SD) age of 72.6 (11.8) years. The decrease in urine cultures before and after the intervention was not significant in intervention sites per segmented regression analysis (-0.04 [95% CI, -0.17 to 0.09]; P = .56). However, difference-in-differences analysis comparing intervention with comparison sites found a significant reduction in the number of urine cultures ordered by 3.24 urine cultures per 1000 bed-days (P = .003). In the segmented regression analyses, the relative percentage decrease of DOT in the postintervention period at the intervention sites was 21.7% (P = .007), from 46.1 (95% CI, 28.8-63.4) to 37.0 (95% CI, 22.6-51.4) per 1000 bed-days. The relative percentage decrease of LOT in the postintervention period at the intervention sites was 21.0% (P = .001), from 36.7 (95% CI, 23.2-50.2) to 29.6 (95% CI, 18.2-41.0) per 1000 bed-days. Conclusions and Relevance: The findings of this quality improvement study suggest that an individualized intervention for antibiotic stewardship for ASB was associated with a decrease in urine cultures and antibiotic use when implemented at multiple sites via external and internal facilitation. The electronic health record database-derived outcome measures and centralized facilitation approach are both suitable for dissemination.

Granulomatous amoebic encephalitis caused by Acanthamoeba in a patient with AIDS: a challenging diagnosis.

INTRODUCTION: Acanthamoeba spp. is a ubiquitous free-living amoeba that causes human infections affecting predominantly the cornea and central nervous system. The diagnosis and treatment of Acanthamoeba encephalitis is very challenging. CASE SUMMARY: A 53-year-old male with HIV/AIDS was admitted for altered mental status and fever. On initial examination, he had left hemianopia with left-sided weakness and numbness. MRI revealed an inflammatory and enhancing parenchymal mass associated with leptomeningeal enhancement in the occipitoparietal lobe containing multiple punctate hemorrhages. He was treated with empiric antibiotics for presumptive toxoplasmosis, brain abscess, fungal infection and tuberculosis with an unremarkable lymphoma work up. Initial brain biopsy studies were unremarkable except for non-specific granulomas and adjacent necrotic tissue. The patient passed away 2.5 months after initial presentation with no diagnosis. Post-mortem testing by the Centers for Disease Control and Prevention (CDC) confirmed the diagnosis of granulomatous amoebic encephalitis (GAE) by visualization with immunohistochemistry staining and PCR. Recovery is rare from GAE likely due to delay in diagnosis. CONCLUSIONS: This case illustrates the importance of including GAE into the differential diagnosis of brain mass. We advocate early molecular testing of tissue specimen by the CDC to achieve an appropriate diagnosis, and a multidisciplinary approach for the management of this condition.

Liver abscess caused by Lawsonella clevelandensis in a patient with rheumatoid arthritis: A case report and literature review.

Lawsonella clevelandensis is a recently described anaerobic and partially acid-fast bacterium within the order Corynebacterineae. It is a fastidious microorganism that has been identified as part of the oral microbiota and is rarely associated with human infections. We describe the case of a 70-year-old man with a history of rheumatoid arthritis that developed liver abscesses and pylephlebitis. Gram stain of purulent material obtained by percutaneous drainage of the hepatic collection revealed gram-positive bacilli that stained acid-fast by the Kinyoun method. The patient was initially treated with imipenem, moxifloxacin and clarithromycin for possible Nocardia and/or nontuberculous mycobacterial infection. Cultures failed to grow the organism seen on the stains, and broad-spectrum 16S rRNA PCR gene sequencing analysis identified it as Lawsonella clevelandensis. Treatment was de-escalated to amoxicillin/clavulanic acid. The hepatic abscesses resolved completely after 4 weeks of treatment. There are only 8 documented cases of human infection caused by Lawsonella clevelandensis reported in the literature. Conventional microbiological methods do not reliably detect this bacterium, and the diagnosis relies on molecular methods. Excellent outcomes are obtained with a combined treatment approach that includes abscess drainage and prolonged antibiotic therapy.

Organizational readiness assessment in acute and long-term care has important implications for antibiotic stewardship for asymptomatic bacteriuria.

BACKGROUND: Prior to implementing an antibiotic stewardship intervention for asymptomatic bacteriuria (ASB), we assessed institutional barriers to change using the Organizational Readiness to Change Assessment. METHODS: Surveys were self-administered on paper in inpatient medicine and long-term care units at 4 Veterans Affairs facilities. Participants included providers, nurses, and pharmacists. The survey included 7 subscales: evidence (perceived strength of evidence) and six context subscales (favorability of organizational context). Responses were scored on a 5-point Likert-type scale. RESULTS: One hundred four surveys were completed (response rate = 69.3%). Overall, the evidence subscale had the highest score; the resources subscale (mean 2.8) was significantly lower than other subscales (P < .001). Scores for budget and staffing resources were lower than scores for training and facility resources (P < .001 for both). Pharmacists had lower scores than providers for the staff culture subscale (P = .04). The site with the lowest scores for resources (mean 2.4) also had lower scores for leadership and lower pharmacist effort devoted to stewardship. CONCLUSIONS: Although healthcare professionals endorsed the evidence about nontreatment of ASB, perceived barriers to antibiotic stewardship included inadequate resources and leadership support. These findings provide targets for tailoring the stewardship intervention to maximize success.

Development of a Standardized Data Collection Tool for Evaluation and Management of Coronavirus Disease 2019.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 ) is responsible for coronavirus disease 2019 (COVID-19), a disease that had not been previously described and for which clinicians need to rapidly adapt their daily practice. The novelty of SARS-CoV-2 produced significant gaps in harmonization of definitions, data collection, and outcome reporting to identify patients who would benefit from potential interventions. METHODS: We describe a multicenter collaboration to develop a comprehensive data collection tool for the evaluation and management of COVID-19 in hospitalized patients. The proposed tool was developed by a multidisciplinary working group of infectious disease physicians, intensivists, and infectious diseases/antimicrobial stewardship pharmacists. The working group regularly reviewed literature to select important patient characteristics, diagnostics, and outcomes for inclusion. The data collection tool consisted of spreadsheets developed to collect data from the electronic medical record and track the clinical course after treatments. RESULTS: Data collection focused on demographics and exposure epidemiology, prior medical history and medications, signs and symptoms, diagnostic test results, interventions, clinical outcomes, and complications. During the pilot validation phase, there was <10% missing data for most domains and components. Team members noted improved efficiency and decision making by using the tool during interdisciplinary rounds. CONCLUSIONS: We present the development of a COVID-19 data collection tool and propose its use to effectively assemble harmonized data of hospitalized individuals with COVID-19. This tool can be used by clinicians, researchers, and quality improvement healthcare teams. It has the potential to facilitate interdisciplinary rounds, provide comparisons across different hospitalized populations, and adapt to emerging challenges posed by the pandemic.