Kartikeya Cherabuddi

Transfer from High-Acuity Long-Term Care Facilities Is Associated with Carriage of Klebsiella pneumoniae Carbapenemase–Producing Enterobacteriaceae: A Multihospital Study

OBJECTIVE To determine whether transfer from a long-term care facility (LTCF) is a risk factor for colonization with Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae upon acute care hospital admission. DESIGN Microbiologic survey and nested case-control study. SETTING Four hospitals in a metropolitan area (Chicago) with an early KPC epidemic. PATIENTS Hospitalized adults. METHODS Patients transferred from LTCFs were matched 1∶1 to patients admitted from the community by age (± 10 years), admitting clinical service, and admission date (± 2 weeks). Rectal swab specimens were collected within 3 days after admission and tested for KPC-producing Enterobacteriaceae. Demographic and clinical information was extracted from medical records. RESULTS One hundred eighty patients from LTCFs were matched to 180 community patients. KPC-producing Enterobacteriaceae colonization was detected in 15 (8.3%) of the LTCF patients and 0 (0%) of the community patients ([Formula: see text]). Prevalence of carriage differed by LTCF subtype: 2 of 135 (1.5%) patients from skilled nursing facilities without ventilator care (SNFs) were colonized upon admission, compared to 9 of 33 (27.3%) patients from skilled nursing facilities with ventilator care (VSNFs) and 4 of 12 (33.3%) patients from long-term acute care hospitals (LTACHs; [Formula: see text]). In a multivariable logistic regression model adjusted for a propensity score that predicted LTCF subtype, patients admitted from VSNFs or LTACHs had 7.0-fold greater odds of colonization (ie, odds ratio; 95% confidence interval, 1.3-42; [Formula: see text]) with KPC-producing Enterobacteriaceae than patients from an SNF. CONCLUSIONS Patients admitted to acute care hospitals from high-acuity LTCFs (ie, VSNFs and LTACHs) were more likely to be colonized with KPC-producing Enterobacteriaceae than were patients admitted from the community. Identification of healthcare facilities with a high prevalence of colonized patients presents an opportunity for focused interventions that may aid regional control efforts.

Zika and Chikungunya virus co-infection in a traveller returning from Colombia, 2016: virus isolation and genetic analysis

Introduction: Zika virus (ZIKV) and Chikungunya virus (CHIKV) can share the same mosquito vector, and co-infections by these viruses can occur in humans. While infections with these viruses share commonalities, CHIKV is unique in causing arthritis and arthralgias that may persist for a year or more. These infections are commonly diagnosed by RT–PCR-based methods during the acute phase of infection. Even with the high specificity and sensitivity characteristic of PCR, false negatives can occur, highlighting the need for additional diagnostic methods for confirmation. Case presentation: On her return to the USA, a traveller to Colombia, South America developed an illness consistent with Zika, Chikungunya and/or Dengue. RT-PCR of her samples was positive only for ZIKV. However, arthralgias persisted for months, raising concerns about co-infection with CHIKV or Mayaro viruses. Cell cultures inoculated with her original clinical samples demonstrated two types of cytopathic effects, and both ZIKV and CHIKV were identified in the supernatants. On phylogenetic analyses, both viruses were found to be related to strains found in Colombia. Conclusion: These findings highlight the need to consider CHIKV co-infection in patients with prolonged rheumatological symptoms after diagnosis with ZIKV, and the usefulness of cell culture as an amplification step for low-viremia blood and other samples.

Potent in vitro and in vivo antifungal activity of a small molecule host defense peptide mimic through a membrane-active mechanism

Lethal systemic fungal infections of Candida species are increasingly common, especially in immune compromised patients. By in vitro screening of small molecule mimics of naturally occurring host defense peptides (HDP), we have identified several active antifungal molecules, which also exhibited potent activity in two mouse models of oral candidiasis. Here we show that one such compound, C4, exhibits a mechanism of action that is similar to the parent HDP upon which it was designed. Specifically, its initial interaction with the anionic microbial membrane is electrostatic, as its fungicidal activity is inhibited by cations. We observed rapid membrane permeabilization to propidium iodide and ATP efflux in response to C4. Unlike the antifungal peptide histatin 5, it did not require energy-dependent transport across the membrane. Rapid membrane disruption was observed by both fluorescence and electron microscopy. The compound was highly active in vitro against numerous fluconazole-resistant clinical isolates of C. albicans and non-albicans species, and it exhibited potent, dose-dependent activity in a mouse model of invasive candidiasis, reducing kidney burden by three logs after 24 hours, and preventing mortality for up to 17 days. Together the results support the development of this class of antifungal drug to treat invasive candidiasis.

Applying athletic principles to medical rounds to improve teaching and patient care.

PROBLEM Teaching hospital multidisciplinary work rounds are often inefficient, delaying the completion of patient care tasks and detracting from teaching. Participants often act as working groups rather than interdependent teams. Athletic principles were used to train multidisciplinary rounding teams to adopt the systems used by manufacturing to improve the efficiency and quality of patient care, as well as teamwork and didactic teaching. APPROACH Experimental groups of general medical rounding teams-faculty member, house staff, medical students, bedside nurses, pharmacists, and a case manager-were introduced to individual job descriptions (playbooks), key customer-supplier relation ships, and efficient communication protocols, accompanied by weekly feed back (game films). A two-phase pilot 11-month prospective trial (February to July 2009 and September 2011 to January 2012) compared the experimental and control rounding teams on the basis of length of stay, 30-day readmission rates, and physician, student, and patient satisfaction. OUTCOMES These interventions resulted in a 30% reduction in 30-day readmissions and, in the 2011-2012 phase, an 18% shorter length of stay. Anonymous surveys documented greater satisfaction of faculty, residents, and medical students, and student ratings of teaching were markedly improved. Patient satisfaction did not change. NEXT STEPS The new rounding system has the potential to reduce waste and improve the quality of patient care while improving caregiver satisfaction and medical student teaching. Adaptive leadership skills will be required to overcome resistance to change. The use of athletic analogies can improve teamwork and facilitate the adoption of a systems approach to the delivery of patient care.

Ampicillin for the treatment of complicated urinary tract infections caused by vancomycin resistant enterococcus spp (VRE): a single-center university hospital experience

Vancomycin-resistant enterococci (VRE) are a common cause of urinary tract infections (UTIs) and are typically multidrug resistant, including ampicillin. This retrospective study evaluated outcomes of 84 adult patients hospitalized between January 2007 and December 2015 with ampicillin- and vancomycin-resistant enterococcus isolates causing UTI and treated with ampicillin. Treatment response was classified as clinical cure and microbiological eradication. Clinical cure was achieved in 88.1% (74/84) of patients. In patients with follow-up cultures, microbiological eradication was achieved in 86% (50/58) of patients. Cure rates were similar in patients with indwelling urinary catheters (n = 45) receiving catheter exchange/removal (90.47%; 19/21) versus catheter retention (87.5%; 21/24). Presence of co-morbidities, such as diabetes and chronic kidney disease, were not associated with increased risk of treatment failure. Immunocompromised patients achieved lower cure rates of 78.1% (25/32) compared with 94.2% (49/52) among those without immune impairment (P = 0.038). Presence of an underlying urinary tract abnormality was also associated with a lower cure rate of 71.4% (15/21) compared with 93.7% (59/63) in those without urinary tract abnormalities (P = 0.0135). Overall cure rates remained high in all groups providing good evidence to support ampicillin for the treatment of complicated UTI caused by ampicillin- and vancomycin-resistant enterococci.

Keystone Virus Isolated From a Florida Teenager With Rash and Subjective Fever: Another Endemic Arbovirus in the Southeastern United States?

Keystone virus, a California-serogroup orthobunyavirus, was first isolated in 1964 from mosquitoes in Keystone, Florida. There were no prior reports of isolation from humans, despite studies suggesting that ~20% of persons living in the region are seropositive. We report virus isolation from a Florida teenager with a rash and fever.

Antimicrobial Stewardship Training for Infectious Diseases Fellows: Program Directors Identify a Curriculum Need

A needs assessment survey of infectious diseases (ID) training program directors identified gaps in educational resources for training and evaluating ID fellows in antimicrobial stewardship. An Infectious Diseases Society of America-sponsored core curriculum was developed to address that need.

Refractory acute respiratory failure due to Pneumocystis jiroveci (PCP) and Cytomegalovirus (CMV) pneumonitis: A case report and review of literature

Highlights • A case report of an HIV patient with refractory acute respiratory failure secondary to Pneumocystis jiroveci (PCP) and Cytomegalovirus (CMV) pneumonitis.• Diagnostic and therapeutic dilemma of treating CMV in such a clinical scenario.• Role of corticosteroids in treatment of PJP and risk factors for CMV.• Characteristic findings on CT scan and BAL cytology.

Antifungal Potential of Host Defense Peptide Mimetics in a Mouse Model of Disseminated Candidiasis

Invasive candidiasis caused by Candida albicans and non-albicans Candida (NAC) present a serious disease threat. Although the echinocandins are recommended as the first line of antifungal drug class, resistance to these agents is beginning to emerge, demonstrating the need for new antifungal agents. Host defense peptides (HDP) exhibit potent antifungal activity, but as drugs they are difficult to manufacture efficiently, and they are often inactivated by serum proteins. HDP mimetics are low molecular weight non-peptide compounds that can alleviate these problems and were shown to be membrane-active against C. albicans and NAC. Here, we expand upon our previous works to describe the in vitro and in vivo activity of 11 new HDP mimetics that are active against C. albicans and NAC that are both sensitive and resistant to standard antifungal drugs. These compounds exhibit minimum inhibitory/fungicidal concentration (MIC/MFC) in the µg/mL range in the presence of serum and are inhibited by divalent cations. Rapid propidium iodide influx into the yeast cells following in vitro exposure suggested that these HDP mimetics were also membrane active. The lead compounds were able to kill C. albicans in an invasive candidiasis CD-1 mouse model with some mimetic candidates decreasing kidney burden by 3–4 logs after 24 h in a dose-dependent manner. The data encouraged further development of this new anti-fungal drug class for invasive candidiasis.

Assessing antimicrobial stewardship initiatives: Clinical evaluation of cefepime or piperacillin/tazobactam in patients with bloodstream infections secondary to AmpC-producing organisms

Management of micro-organisms harbouring AmpC β-lactamases remains challenging. Carbapenems are often considered first-line agents. Due to growing concern regarding carbapenem-resistant Enterobacteriaceae, integrating non-carbapenem treatment strategies is being explored for these pathogens. The primary objective of this study was to evaluate clinical outcomes in patients with bacteraemia secondary to AmpC-producing organisms treated with cefepime or piperacillin/tazobactam (TZP). A retrospective study of adult patients receiving cefepime or TZP for the treatment of AmpC -producing organisms with positive cefoxitin screen (i.e. Citrobacter, Enterobacter or Serratia spp. along with cefoxitin resistance) isolated from blood cultures was conducted. The primary endpoint was clinical cure at end of therapy (EOT). Secondary endpoints included microbiological eradication, frequency of susceptibility changes following treatment, and 7- and 30-day all-cause mortality. Clinical cure at EOT was 87.1%, with 93.2% of patients achieving microbiological eradication. The 7- and 30-day mortality rates were 3.8% and 10.6%, respectively. Organism susceptibility was exceptionally high, with minimum inhibitory concentrations (MICs) of ≤2 μg/mL in 90% of patients treated with cefepime (n = 108). Selection for resistance to third-generation cephalosporins or primary antimicrobial therapy was infrequent at 6.1% (8/132). In conclusion, use of cefepime or TZP for management of AmpC bloodstream infections was associated with clinical and microbiological cure with infrequent selection for resistance.