Brincidofovir for disease progression due to suspected tecovirimat resistance in association with advanced HIV.

A man with advanced HIV presented with verrucous plaques 2-3 months after initial mpox infection. He received two courses of tecovirimat without resolution of initial mpox lesions and development of new lesions raising concern for resistance. He was treated with two doses of brincidofovir and demonstrated improvement 6 months later.

Re-evaluation of cefepime or piperacillin/tazobactam to decrease use of carbapenems in ESBL-producing Enterobacterales urinary tract infections (REDUCE-UTI).

Objectives: To re-examine the use of non-carbapenems (NCBPs), specifically piperacillin/tazobactam and cefepime, for ESBL-producing Enterobacterales (ESBL-E) urinary tract infections (UTIs). Patients: Retrospective cohort study of adults hospitalized between January 2016 and June 2020 with pyuria on urinalysis, a urine culture positive for ESBL-E treated with a study antibiotic (meropenem, ertapenem, cefepime or piperacillin/tazobactam) and did not meet criteria for study exclusion. Methods: To compare carbapenems (CBPs) with cefepime or piperacillin/tazobactam for the treatment of ESBL-E UTI. The primary outcome was clinical cure, defined as complete resolution of signs and symptoms of infection. Secondary outcomes included in-hospital mortality, recurrence within 30 days and resistance emergence within 30 days. Results: One-hundred and thirty-three patients were included, based on definitive therapy received; 69 (51.9%) received CBP and 64 (48.1%) received NCBP therapy. Of the total patient population, 17 (12.8%) were admitted to the ICU, 84 (63.1%) had a complicated UTI and 64 (48.1%) had pyelonephritis. There was no difference in clinical cure between the CBP and NCBP groups (95.7% versus 96.9%, P = 0.999). Additionally, no differences in secondary outcomes were observed. Conclusions: When compared with CBPs, cefepime and piperacillin/tazobactam resulted in similar clinical cure, in-hospital mortality, recurrence and resistance emergence in the treatment of ESBL-E UTI.

Digital cough monitoring - A potential predictive acoustic biomarker of clinical outcomes in hospitalized COVID-19 patients.

PURPOSE: Recent developments in the field of artificial intelligence and acoustics have made it possible to objectively monitor cough in clinical and ambulatory settings. We hypothesized that time patterns of objectively measured cough in COVID-19 patients could predict clinical prognosis and help rapidly identify patients at high risk of intubation or death. METHODS: One hundred and twenty-three patients hospitalized with COVID-19 were enrolled at University of Florida Health Shands and the Centre Hospitalier de l'Université de Montréal. Patients' cough was continuously monitored digitally along with clinical severity of disease until hospital discharge, intubation, or death. The natural history of cough in hospitalized COVID-19 disease was described and logistic models fitted on cough time patterns were used to predict clinical outcomes. RESULTS: In both cohorts, higher early coughing rates were associated with more favorable clinical outcomes. The transitional cough rate, or maximum cough per hour rate predicting unfavorable outcomes, was 3·40 and the AUC for cough frequency as a predictor of unfavorable outcomes was 0·761. The initial 6 h (0·792) and 24 h (0·719) post-enrolment observation periods confirmed this association and showed similar predictive value. INTERPRETATION: Digital cough monitoring could be used as a prognosis biomarker to predict unfavorable clinical outcomes in COVID-19 disease. With early sampling periods showing good predictive value, this digital biomarker could be combined with clinical and paraclinical evaluation and is well adapted for triaging patients in overwhelmed or resources-limited health programs.

Use of therapeutic drug monitoring to characterize cefepime-related neurotoxicity.

STUDY OBJECTIVES: Data evaluating cefepime thresholds associated with neurotoxicity remain limited. The objectives of this study were to evaluate the incidence of cefepime-related neurotoxicity (CRN) in patients with plasma cefepime concentrations, assess the relationship between cefepime exposure and CRN, investigate clinical factors associated with CRN, and describe electroencephalogram (EEG) abnormalities in CRN. DESIGN: This was a retrospective study of adult inpatients admitted between 2016 and 2018 who received cefepime therapeutic drug monitoring (TDM). Potential CRN cases were identified utilizing a standard definition. The primary outcomes of the study were to determine the incidence of CRN and evaluate the relationship between cefepime trough concentrations, the average daily AUC, and neurotoxicity. Bayesian posteriors were generated for each patient using a cefepime pharmacokinetic (PK) model, and the mean daily area under the concentration-time curve (AUC) was calculated. Multiple regression was performed to assess the association between CRN, cefepime PK, and clinical predictors of neurotoxicity. MAIN RESULTS: Four hundred eighty-one patients with 503 hospital encounters received cefepime TDM and were included in the analysis. The incidence of CRN was 4.4% (22/503). Patients with CRN had a higher incidence of renal dysfunction, hypertension, and diabetes mellitus compared to patients without CRN (non-NT). The mean cefepime trough concentration was significantly greater in the CRN patients than in the non-NT group (61.8 ± 33.7 vs. 30 ± 27.7 mg/L, respectively, p = 0.0002). Cefepime trough concentration and renal dysfunction were independently associated with increased risk of CRN in the adjusted multiple regression model. Moderate generalized slowing of the background rhythm was the most common EEG pattern associated with CRN. Delaying cefepime TDM greater than 72 h after the initiation of cefepime was associated with a 3-fold increased risk of CRN. CONCLUSION: Cefepime should be used cautiously in hospitalized patients with renal dysfunction due to the risk of neurotoxicity. Dose optimization utilizing TDM early in cefepime treatment may minimize adverse effects and improve patient safety.

Re-evaluation of cefepime or piperacillin-tazobactam to decrease use of carbapenems in extended-spectrum beta-lactamase-producing Enterobacterales bloodstream infections (REDUCE-BSI).

Objective: To re-examine the use of noncarbapenems (NCBPs), specifically piperacillin-tazobactam (PTZ) and cefepime (FEP), for extended-spectrum beta-lactamase-producing Enterobacterales bloodstream infections (ESBL-E BSIs). Design: Retrospective cohort study. Setting: Tertiary-care, academic medical center. Patients: The study included patients hospitalized between May 2016 and May 2019 with a positive blood culture for ESBL-E. Patients were excluded if they received treatment with antibiotics other than meropenem, ertapenem, PTZ, or FEP. Patients were also excluded if they were aged <18 years, received antibiotics for <24 hours, were treated for polymicrobial BSI, or received concomitant antibiotic therapy for a separate gram-negative infection. Methods: We compared CBPs with FEP or PTZ for the treatment of ESBL-E BSI. The primary outcome was in-hospital mortality. Secondary outcomes included clinical cure, microbiologic cure, infection recurrence, and resistance development. Results: Data from 114 patients were collected and analyzed; 74 (65%) patients received carbapenem (CBP) therapy and 40 (35%) patients received a NCBP (30 received FEP and 10 received PTZ). The overall in-hospital mortality was 6% (N = 7), with a higher death rate in the CBP arm than in the N-CBP arm, (8% vs 3%; P = .42). No difference in mortality was detected between subgroups with Pitt bacteremia score ≥4, those requiring ICU admission, those whose infections were cause by a nongenitourinary source or causative organism (ie, 76 had Escherichia coli and 38 had Klebsiella spp). We detected no differences in secondary outcomes between the groups. Conclusion: Compared to CBPs, FEP and PTZ did not result in greater mortality or decreased clinical efficacy for the treatment of ESBL-E BSI caused by susceptible organisms.

Implementation of a ß-lactam therapeutic drug monitoring program: Experience from a large academic medical center.

PURPOSE: To describe the implementation and operationalization of a ß-lactam (BL) therapeutic drug monitoring (TDM) program at a large academic center. SUMMARY: BLs are the most used class of antibiotics. Suboptimal antibiotic exposure is a significant concern in hospitalized patients, particularly in those with altered pharmacokinetics. BL-TDM provides clinicians the opportunity to optimize drug concentrations to ensure maximal therapeutic efficacy while minimizing toxicity. However, BL-TDM has not been widely adopted due to the lack of access to assays. The University of Florida Shands Hospital developed a BL-TDM program in 2015. This is a consultative service primarily run by pharmacists and is conducted in all patient care areas. An analysis was performed on the first BL-TDM encounter for 1,438 patients. BL-TDM was most frequently performed for cefepime (61%, n = 882), piperacillin (15%, n = 218), and meropenem (11%, n = 151). BL-TDM was performed a median of 3 days (interquartile range, 1-5 days) from BL initiation. Among patients with available minimum inhibitory concentration (MIC) values and trough concentrations, the pharmacokinetic/pharmacodynamic (PK/PD) target of 100% fT>MIC was attained in 308 patients (88%). BL-TDM resulted in a dosage adjustment in 25% (n = 361) of patients. CONCLUSION: Implementation of a BL-TDM program requires the concerted efforts of physicians, pharmacists, nursing staff, phlebotomists, and personnel in the analytical laboratory. Standard antibiotic dosing failed to achieve optimal PK/PD targets in all patients; utilizing BL-TDM, dose adjustments were made in 1 of every 4 patients.

Use of Novel Strategies to Develop Guidelines for Management of Pyogenic Osteomyelitis in Adults: A WikiGuidelines Group Consensus Statement.

Importance: Traditional approaches to practice guidelines frequently result in dissociation between strength of recommendation and quality of evidence. Objective: To construct a clinical guideline for pyogenic osteomyelitis management, with a new standard of evidence to resolve the gap between strength of recommendation and quality of evidence, through the use of a novel open access approach utilizing social media tools. Evidence Review: This consensus statement and systematic review study used a novel approach from the WikiGuidelines Group, an open access collaborative research project, to construct clinical guidelines for pyogenic osteomyelitis. In June 2021 and February 2022, authors recruited via social media conducted multiple PubMed literature searches, including all years and languages, regarding osteomyelitis management; criteria for article quality and inclusion were specified in the group's charter. The GRADE system for evaluating evidence was not used based on previously published concerns regarding the potential dissociation between strength of recommendation and quality of evidence. Instead, the charter required that clear recommendations be made only when reproducible, prospective, controlled studies provided hypothesis-confirming evidence. In the absence of such data, clinical reviews were drafted to discuss pros and cons of care choices. Both clear recommendations and clinical reviews were planned with the intention to be regularly updated as new data become available. Findings: Sixty-three participants with diverse expertise from 8 countries developed the group's charter and its first guideline on pyogenic osteomyelitis. These participants included both nonacademic and academic physicians and pharmacists specializing in general internal medicine or hospital medicine, infectious diseases, orthopedic surgery, pharmacology, and medical microbiology. Of the 7 questions addressed in the guideline, 2 clear recommendations were offered for the use of oral antibiotic therapy and the duration of therapy. In addition, 5 clinical reviews were authored addressing diagnosis, approaches to osteomyelitis underlying a pressure ulcer, timing for the administration of empirical therapy, specific antimicrobial options (including empirical regimens, use of antimicrobials targeting resistant pathogens, the role of bone penetration, and the use of rifampin as adjunctive therapy), and the role of biomarkers and imaging to assess responses to therapy. Conclusions and Relevance: The WikiGuidelines approach offers a novel methodology for clinical guideline development that precludes recommendations based on low-quality data or opinion. The primary limitation is the need for more rigorous clinical investigations, enabling additional clear recommendations for clinical questions currently unresolved by high-quality data.

Resource Over-Utilization in Hospitalized Patients With Uncomplicated Skin and Soft Tissue Infections.

BACKGROUND: Inpatient management of SSTIs utilizes considerable healthcare resources. The CREST+SEWS score categorizes patients with SSTIs into 4 severity classes. Hospitalizations can be avoided in Class I as they are treated as outpatients with oral antibiotics, whereas Class IV require hospitalization for intravenous antibiotics. OBJECTIVE: The purpose of this study was to perform a budget impact analysis on CREST+SEWS Class 1 patients, to compare the medical costs of current treatment, in the inpatient setting with intravenous antibiotics, with a proposed alternative of using oral antibiotics in the outpatient setting. Further, resource utilization in Class I was evaluated. METHODS: This was a retrospective study of adult patients hospitalized in 2015 for SSTIs who received >24 hours of antimicrobials. The CREST+SEWS scoring system was used to stratify patients into Class I to IV. Pharmacy and medical costs and resources associated with inpatient management of Class I SSTIs were derived from the itemized discharge records. RESULTS: Of the 252 patients who met the inclusion criteria, 61 (24%) were classified as Class I. The total cost of treating Class I SSTI patients in the inpatient setting was $281,816 (cost per patient: $4,619) in 2015 USD. In the hypothetical situation of treatment with oral antibiotics in the outpatient setting, the cost savings were estimated to be $4,398 per patient. Fifty-three percent of patients had blood cultures, and on average, each patient received 2 radiographic tests. CONCLUSIONS: Identifying outpatient candidates, and avoiding tests with low diagnostic can reduce the economic burden of SSTIs.

Cefepime Precision Dosing Tool: from Standard to Precise Dose Using Nonparametric Population Pharmacokinetics.

Cefepime is the second most common cephalosporin used in U.S. hospitals. We aim to develop and validate a cefepime population pharmacokinetic (PK) model and integrate it into a precision dosing tool for implementation. Two data sets (680 patients) were used to build the cefepime PK model in Pmetrics, and three data sets (34 patients) were used for the validation. A separate application data set (115 patients) was used for the implementation and validation of a precision dosing tool. The model support points and covariates were used to generate the optimal initial dose (OID). Cefepime PK was described by a two-compartment model including weight and creatinine clearance (CrCl) as covariates. The median rate of elimination was 0.30 h-1 (adults) and 0.96 h-1 (children), the central volume of distribution was 13.85 L, and the rate of transfer from the central to the peripheral compartments was 1.22 h-1 and from the peripheral to the central compartments was 1.38 h-1. After integration in BestDose, the observed versus predicted cefepime concentration fit using the application data set was excellent (R2 > 0.98), and the median difference between what was observed and what BestDose predicted on a second occasion was 4%. For the OID, cefepime at a 0.5- to 1-g 4-h infusion every 8 to 24 h (q8 to 24 h) with a CrCl of <70 mL/min was needed to achieve a target range of free trough:MIC 1 to 4 at a MIC of 8 mg/L, while continuous infusion was needed for higher CrCl and weight values. In conclusion, we developed and validated a cefepime model for clinical application. The model was integrated in a precision dosing tool for implementation, and the median concentration prediction bias was 4%. The OID algorithm was provided.

Vaccine Enthusiasm and Hesitancy in Cancer Patients and the Impact of a Webinar.

(1) Background: Vaccine hesitancy and rejection are major threats to controlling coronavirus disease 2019 (COVID-19). There is a paucity of information about the attitudes of cancer patients towards vaccinations and the role of clinical oncologists in influencing vaccination acceptance. (2) Methods: Cancer patients and caregivers were invited to participate in a webinar and two surveys (pre- and post-webinar) assessing intention and thought processes associated with receiving COVID-19 vaccines. (3) Results: Two hundred and sixty-four participants participated in the webinar and registered to take at least one survey. Participants reported receiving most of their COVID-19 vaccine information from their doctor, clinic, or hospital. Before the webinar, 71% of participants reported the intention to receive a COVID-19 vaccine, 24% were unsure, and 5% had no intention of receiving a vaccine. The strongest predictors of vaccine enthusiasm were (a) planning to encourage the vaccination of family, friends, co-workers, and community, and (b) physician recommendation. The chief reason for vaccine hesitancy was a fear of side effects. After the webinar, 82.5% reported the intention to receive a vaccine, 15.4% were still unsure, and 2% stated that they had no intention of receiving a vaccine. The webinar shifted the attitude towards vaccine enthusiasm, despite an already vaccine-enthusiastic population. Communicating about vaccines using positive framing is associated with greater vaccine enthusiasm. (4) Conclusions: Patient education programs co-hosted by multiple stakeholders and delivered by oncologists can increase cancer patient enthusiasm for COVID-19 vaccination.

Investing in the Future: A Role for Professional Societies to Prepare the Next Generation of Healthcare Leaders Through Curriculum Development and Dissemination.

Professional societies serve many functions that benefit constituents; however, few professional societies have undertaken the development and dissemination of formal, national curricula to train the future workforce while simultaneously addressing significant healthcare needs. The Infectious Diseases Society of America (IDSA) has developed 2 curricula for the specific purpose of training the next generation of clinicians to ensure the future infectious diseases (ID) workforce is optimally trained to lead antimicrobial stewardship programs and equipped to meet the challenges of multidrug resistance, patient safety, and healthcare quality improvement. A core curriculum was developed to provide a foundation in antimicrobial stewardship for all ID fellows, regardless of career path. An advanced curriculum was developed for ID fellows specifically pursuing a career in antimicrobial stewardship. Both curricula will be broadly available in the summer of 2021 through the IDSA website.

In-Frame 12-Nucleotide Deletion within Open Reading Frame 3a in a SARS-CoV-2 Strain Isolated from a Patient Hospitalized with COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain UF-8, with an in-frame 12-nucleotide deletion within open reading frame 3a (ORF3a), was isolated from a 78-year-old COVID-19 patient in March 2020.

Performance of a Semiquantitative Multiplex Bacterial and Viral PCR Panel Compared With Standard Microbiological Laboratory Results: 396 Patients Studied With the BioFire Pneumonia Panel.

BACKGROUND: Microbiologic results are critical to optimal management of patients with lower respiratory tract infection, but standard methods may take several days. The multiplex polymerase chain reaction BioFire Pneumonia (PN) panel detects 15 common bacterial species semiquantitatively as copy number/mL, 8 viral species, and 7 resistance genes in about an hour within the clinical laboratory. METHODS: We tested 396 unique endotracheal or bronchoalveolar lavage specimens with the BioFire Pneumonia panel and compared the bacterial detections to conventional gram stain and culture results. RESULTS: Of the 396 patients, 138 grew at least 1 bacterium that had a target on the PN panel, and 136/138 (98.6%) were detected by the panel. A total of 177 isolates were recovered in culture and the PN panel detected 174/177 (98.3%). A further 20% of patients had additional targets detected that were not found on standard culture (specificity 69%, positive predictive value 63%, and negative predictive value 98.9%). Copy number was strongly related to standard semiquantitative growth on plates reported by the laboratory (eg, 1+, 2+, 3+ growths) and was significantly higher in those specimens that grew a potential pathogen. Both higher copy number and bacterial detections found by the PN panel, but not found in culture, were strongly positively related to the level of white blood cells reported in the initial gram stain. CONCLUSIONS: Higher copy number and bacterial detections by the PN panel are related to the host respiratory tract inflammatory response. If laboratories can achieve a rapid turnaround time, the PN panel should have a significant impact both on patient management and on antibiotic stewardship.

Viable SARS-CoV-2 in the air of a hospital room with COVID-19 patients.

OBJECTIVES: Because the detection of SARS-CoV-2 RNA in aerosols but failure to isolate viable (infectious) virus are commonly reported, there is substantial controversy whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can be transmitted through aerosols. This conundrum occurs because common air samplers can inactivate virions through their harsh collection processes. We sought to resolve the question whether viable SARS-CoV-2 can occur in aerosols using VIVAS air samplers that operate on a gentle water vapor condensation principle. METHODS: Air samples collected in the hospital room of two coronavirus disease-2019 (COVID-19) patients, one ready for discharge and the other newly admitted, were subjected to RT-qPCR and virus culture. The genomes of the SARS-CoV-2 collected from the air and isolated in cell culture were sequenced. RESULTS: Viable SARS-CoV-2 was isolated from air samples collected 2 to 4.8 m away from the patients. The genome sequence of the SARS-CoV-2 strain isolated from the material collected by the air samplers was identical to that isolated from the newly admitted patient. Estimates of viable viral concentrations ranged from 6 to 74 TCID50 units/L of air. CONCLUSIONS: Patients with respiratory manifestations of COVID-19 produce aerosols in the absence of aerosol-generating procedures that contain viable SARS-CoV-2, and these aerosols may serve as a source of transmission of the virus.

Early therapeutic monitoring of ß-lactams and associated therapy outcomes in critically ill patients.

BACKGROUND: In the ICU, early and appropriate antimicrobial therapy is important to lower infection-related mortality. OBJECTIVES: Assess whether achieving early ß-lactam free concentration above the MIC 100% of the time (fT>MIC) is associated with positive outcomes in the ICU. METHODS: This retrospective study was conducted in ICU patients admitted to UF Health Shands Hospital between 2016 and 2018. Adult patients who received ß-lactam therapy and had drug concentration measured were included. Data collected included demographics, ß-lactam regimens and concentrations, sources of infection, cultures and susceptibilities, mortality, length of stay, resistance acquisition for 30 days and clinical outcome at end of therapy. Multiple regression and time-to-event (TTE) analyses were performed. RESULTS: Two-hundred and six patients were included. Clinical cure occurred in 71%, microbial eradication occurred in 58% and new resistance to the ß-lactam received developed in 8% of patients. Hospital and 30 day mortalities were 17% and 14%, respectively. fT>MIC and fT>4×MIC were associated with clinical cure (P = 0.0303), microbial eradication (P = 0.0476) and suppression of resistance (P = 0.0043). Delay in measuring ß-lactam concentration was associated with clinical failure (P = 0.0072), longer ICU stay (P < 0.0001) and higher mortality (P = 0.0387). In the TTE analysis, patients with 100% fT>MIC had a significantly shorter ICU stay (P = 0.0297). Patients who had clinical cure and microbial eradication had drug concentrations measured earlier (P = 0.0025 and 0.0254, respectively). CONCLUSIONS: This study highlights the importance of early measurement of ß-lactam concentration and confirms the association between fT>MIC and clinical cure, microbial eradication and emergence of resistance.

Viable SARS-CoV-2 in the air of a hospital room with COVID-19 patients.

Background - There currently is substantial controversy about the role played by SARS-CoV-2 in aerosols in disease transmission, due in part to detections of viral RNA but failures to isolate viable virus from clinically generated aerosols. Methods - Air samples were collected in the room of two COVID-19 patients, one of whom had an active respiratory infection with a nasopharyngeal (NP) swab positive for SARS-CoV-2 by RT-qPCR. By using VIVAS air samplers that operate on a gentle water-vapor condensation principle, material was collected from room air and subjected to RT-qPCR and virus culture. The genomes of the SARS-CoV-2 collected from the air and of virus isolated in cell culture from air sampling and from a NP swab from a newly admitted patient in the room were sequenced. Findings - Viable virus was isolated from air samples collected 2 to 4.8m away from the patients. The genome sequence of the SARS-CoV-2 strain isolated from the material collected by the air samplers was identical to that isolated from the NP swab from the patient with an active infection. Estimates of viable viral concentrations ranged from 6 to 74 TCID50 units/L of air. Interpretation - Patients with respiratory manifestations of COVID-19 produce aerosols in the absence of aerosol-generating procedures that contain viable SARS-CoV-2, and these aerosols may serve as a source of transmission of the virus.

Population Pharmacokinetics and Target Attainment of Cefepime in Critically Ill Patients and Guidance for Initial Dosing.

Cefepime is commonly used in the intensive care unit (ICU) to treat bacterial infections. The time during which the free cefepime concentration is above the MIC (fT>MIC) should be optimized to increase the efficacy of the regimen. We aim to optimize the exposure of cefepime in ICU patients by using population pharmacokinetic (PK) modeling and simulations. Two data sets were included in this study. The first was a prospective study of pediatric patients who received cefepime at 50 mg/kg of body weight and had extensive PK sampling. The second study comprised retrospective data for adult ICU patients admitted to UF Health Shands Hospital who received cefepime and had their cefepime concentrations measured. The population PK model was developed, and simulations were performed, using Pmetrics. The target exposures were 100% fT>MIC and 100% fT>4×MIC The studies included a total of 266 patients, and the mean ages were 3.9 years in the pediatric group and 55 years in adult group. More than half of the patients were males. The mean (standard deviation [SD]) creatinine clearance (CrCl) was 125 (93) ml/min. The mean (SD) daily dose for adults was 4.9 (1.6) g. Cefepime was well described by a two-compartment model with weight as a covariate on the volume of distribution and elimination rate constant (kel), and CrCl and age group as covariates on kel At a MIC of 8 mg/liter, a cefepime loading dose of 4 g as an extended infusion followed by a 6-g continuous infusion was needed for good target attainment. In conclusion, prolonged or continuous infusions will be needed to achieve optimal cefepime exposure for ICU patients. Given the observed variability, therapeutic drug monitoring can help individualize therapy.

Chloroquine and hydroxychloroquine in the context of COVID-19.

Chloroquine and closely related structural analogs, employed initially for the treatment of malaria, are now gaining worldwide attention due to the rapidly spreading pandemic caused by severe acute respiratory syndrome-coronavirus-2, named coronavirus disease (COVID) of 2019 (COVID-19). Although much of this attention has a mechanistic basis, the hard efficacy data for chloroquine/hydroxychloroquine in the management of the clinical syndrome of COVID-19 have been limited thus far. This review aims to present the available in vitro and clinical data for the role of chloroquine/hydroxychloroquine in COVID-19 and attempts to put them into perspective, especially in relation to the different risks/benefits particular to each patient who may require treatment.

Clostridioides difficile associated peritonitis in peritoneal dialysis patients - a case series based review of an under-recognized entity with therapeutic challenges.

BACKGROUND: Initial presentation of peritoneal dialysis associated infectious peritonitis can be clinically indistinguishable from Clostridioides difficile infection (CDI) and both may demonstrate a cloudy dialysate. Empiric treatment of the former entails use of 3rd-generation cephalosporins, which could worsen CDI. We present a logical management approach of this clinical scenario providing examples of two cases with CDI associated peritonitis of varying severity where the initial picture was concerning for peritonitis and treatment for CDI resulted in successful cure. CASE PRESENTATION: A 73-year-old male with ESRD managed with PD presented with fever, abdominal pain, leukocytosis and significant diarrhea. Cell count of the peritoneal dialysis effluent revealed 1050 WBCs/mm3 with 71% neutrophils. C. difficile PCR on the stool was positive. Patient was started on intra-peritoneal (IP) cefepime and vancomycin for treatment of the peritonitis and intravenous (IV) metronidazole and oral vancomycin for treatment of the C. difficile colitis but worsened. PD fluid culture showed no growth. He responded well to IV tigecycline, oral vancomycin and vancomycin enemas. Similarly, a 55-year-old male with ESRD with PD developed acute diarrhea and on the third day noted a cloudy effluent from his dialysis catheter. PD fluid analysis showed 1450 WBCs/mm3 with 49% neutrophils. IP cefepime and vancomycin were initiated. CT of the abdomen showed rectosigmoid colitis. C. difficile PCR on the stool was positive. IP cefepime and vancomycin were promptly discontinued. Treatment with oral vancomycin 125 mg every six hours and IV Tigecycline was initiated. PD fluid culture produced no growth. PD catheter was retained. CONCLUSIONS: In patients presenting with diarrhea with risk factors for CDI, traditional empiric treatment of PD peritonitis may need to be reexamined as they could have detrimental effects on CDI course and patient outcomes.