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1.
Am J Transplant ; 23(12): 1995-1999, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37516244

ABSTRACT

In 2022, a global outbreak of mpox (formerly known as monkeypox) was reported outside of areas considered endemic for the disease, predominantly in persons identifying as men who have sex with men, gay, or bisexual. To date, 3 cases of mpox in solid organ transplant recipients have been published; however, no instances of secondary transmission among solid organ transplant recipients have been reported. Here, we report a case of a 53-year-old male kidney transplant recipient who contracted mpox while caring for a household contact with the disease. The patient's clinical and laboratory findings during his rapidly fatal course, autopsy findings, and genomics analysis are presented, emphasizing the need for expanded pre-exposure prophylaxis efforts in patient populations without the risk factors prioritized by public health authorities for vaccination.


Subject(s)
Kidney Transplantation , Mpox (monkeypox) , Sexual and Gender Minorities , Male , Humans , Middle Aged , Homosexuality, Male , Kidney Transplantation/adverse effects , Disease Outbreaks
2.
Am J Transplant ; 22(1): 96-112, 2022 01.
Article in English | MEDLINE | ID: mdl-34212491

ABSTRACT

Antimicrobial stewardship programs (ASPs) have made immense strides in optimizing antibiotic, antifungal, and antiviral use in clinical settings. However, although ASPs are required institutionally by regulatory agencies in the United States and Canada, they are not mandated for transplant centers or programs specifically. Despite the fact that solid organ transplant recipients in particular are at increased risk of infections from multidrug-resistant organisms, due to host and donor factors and immunosuppressive therapy, there currently are little rigorous data regarding stewardship practices in solid organ transplant populations, and thus, no transplant-specific requirements currently exist. Further complicating matters, transplant patients have a wide range of variability regarding their susceptibility to infection, as factors such as surgery of transplant, intensity of immunosuppression, and presence of drains or catheters in situ may modify the risk of infection. As such, it is not feasible to have a "one-size-fits-all" style of stewardship for this patient population. The objective of this white paper is to identify opportunities, risk factors, and ASP strategies that should be assessed with solid organ transplant recipients to optimize antimicrobial use, while producing an overall improvement in patient outcomes. We hope it may serve as a springboard for development of future guidance and identification of research opportunities.


Subject(s)
Antimicrobial Stewardship , Organ Transplantation , Anti-Bacterial Agents/therapeutic use , Humans , Tissue Donors , Transplant Recipients , United States
3.
Antimicrob Agents Chemother ; 66(7): e0005322, 2022 07 19.
Article in English | MEDLINE | ID: mdl-35770999

ABSTRACT

Candida auris is an urgent antimicrobial resistance threat due to its global emergence, high mortality, and persistent transmissions. Nearly half of C. auris clinical and surveillance cases in the United States are from the New York and New Jersey Metropolitan area. We performed genome, and drug-resistance analysis of C. auris isolates from a patient who underwent multi-visceral transplantation. Whole-genome comparisons of 19 isolates, collected over 72 days, revealed closed similarity (Average Nucleotide Identity > 0.9996; Aligned Percentage > 0.9764) and a distinct subcluster of NY C. auris South Asia Clade I. All isolates had azole-linked resistance in ERG11(K143R) and CDR1(V704L). Echinocandin resistance first appeared with FKS1(S639Y) mutation and then a unique FKS1(F635C) mutation. Flucytosine-resistant isolates had mutations in FCY1, FUR1, and ADE17. Two pan-drug-resistant C. auris isolates had uracil phosphoribosyltransferase deletion (FUR1[1Δ33]) and the elimination of FUR1 expression, confirmed by a qPCR test developed in this study. Besides ERG11 mutations, four amphotericin B-resistant isolates showed no distinct nonsynonymous variants suggesting unknown genetic elements driving the resistance. Pan-drug-resistant C. auris isolates were not susceptible to two-drug antifungal combinations tested by checkerboard, Etest, and time-kill methods. The fungal population pattern, discerned from SNP phylogenetic analysis, was consistent with in-hospital or inpatient evolution of C. auris isolates circulating locally and not indicative of a recent introduction from elsewhere. The emergence of pan-drug-resistance to four major classes of antifungals in C. auris is alarming. Patients at high risk for drug-resistant C. auris might require novel therapeutic strategies and targeted pre-and/or posttransplant surveillance.


Subject(s)
Antifungal Agents , Drug Resistance, Fungal , Antifungal Agents/pharmacology , Candida auris , Drug Resistance, Fungal/genetics , Humans , Microbial Sensitivity Tests , Phylogeny
4.
BMC Infect Dis ; 22(1): 400, 2022 Apr 24.
Article in English | MEDLINE | ID: mdl-35462538

ABSTRACT

BACKGROUND: Healthcare-associated infections pose a potentially fatal threat to patients worldwide and Staphylococcus aureus is one of the most common causes of healthcare-associated infections. S. aureus is a common commensal pathogen and a frequent cause of bacteremia, with studies demonstrating that nasal and blood isolates from single patients match more than 80% of the time. Here we report on a contemporary collection of colonizing isolates from those with methicillin-resistant S. aureus (MRSA) bloodstream infections to evaluate the diversity within hosts, and detail the clinical features associated with concomitant nasal colonization. METHODS: Swabs of the bilateral anterior nares were obtained from patients diagnosed with MRSA bacteremia. A single colony culture from the blood and an average of 6 colonies from the nares were evaluated for MRSA growth. For the nares cultures, we typed multiple isolates for staphylococcal protein A (spa) and derived the clonal complexes. Demographic and clinical data were obtained retrospectively from the electronic medical record system and analysed using univariate and multivariable regression models. RESULTS: Over an 11-month period, 68 patients were diagnosed with MRSA bloodstream infection, 53 were swabbed, and 37 (70%) were colonized with MRSA in the anterior nares. We performed molecular typing on 213 nasal colonies. Spa types and clonal complexes found in the blood were also detected in the nares in 95% of the cases. We also found that 11% of patients carried more than one clone of MRSA in the nares. Male sex and history of prior hospitalization within the past 90 days increased odds for MRSA colonization. CONCLUSION: The molecular epidemiological landscape of colonization in the setting of invasive disease is diverse and defining the interplay between colonization and invasive disease is critical to combating invasive MRSA disease.


Subject(s)
Bacteremia , Cross Infection , Methicillin-Resistant Staphylococcus aureus , Staphylococcal Infections , Bacteremia/epidemiology , Carrier State , Cross Infection/epidemiology , Humans , Male , Methicillin-Resistant Staphylococcus aureus/genetics , Nose , Retrospective Studies , Staphylococcal Infections/epidemiology , Staphylococcus aureus
5.
Clin Transplant ; 35(4): e14239, 2021 04.
Article in English | MEDLINE | ID: mdl-33527453

ABSTRACT

The impact of pre-transplant (SOT) carbapenem-resistant Enterobacterales (CRE) colonization or infection on post-SOT outcomes is unclear. We conducted a multi-center, international, cohort study of SOT recipients, with microbiologically diagnosed CRE colonization and/or infection pre-SOT. Sixty adult SOT recipients were included (liver n = 30, hearts n = 17). Klebsiella pneumoniae (n = 47, 78%) was the most common pre-SOT CRE species. Median time from CRE detection to SOT was 2.32 months (IQR 0.33-10.13). Post-SOT CRE infection occurred in 40% (n = 24/60), at a median of 9 days (IQR 7-17), and most commonly due to K pneumoniae (n = 20/24, 83%). Of those infected, 62% had a surgical site infection, and 46% had bloodstream infection. Patients with post-SOT CRE infection more commonly had a liver transplant (16, 67% vs. 14, 39%; p =.0350) or pre-SOT CRE BSI (11, 46% vs. 7, 19%; p =.03). One-year post-SOT survival was 77%, and those with post-SOT CRE infection had a 50% less chance of survival vs. uninfected (0.86, 95% CI, 0.76-0.97 vs. 0.34, 95% CI 0.08-1.0, p =.0204). Pre-SOT CRE infection or colonization is not an absolute contraindication to SOT and is more common among abdominal SOT recipients, those with pre-SOT CRE BSI, and those with early post-SOT medical and surgical complications.


Subject(s)
Carbapenems , Organ Transplantation , Adult , Anti-Bacterial Agents/therapeutic use , Cohort Studies , Humans , Klebsiella pneumoniae , Organ Transplantation/adverse effects , Transplant Recipients
6.
J Clin Microbiol ; 58(2)2020 01 28.
Article in English | MEDLINE | ID: mdl-31694974

ABSTRACT

From 2015 to 2017, 11 confirmed brucellosis cases were reported in New York City, leading to 10 Brucella exposure risk events (Brucella events) in 7 clinical laboratories (CLs). Most patients had traveled to countries where brucellosis is endemic and presented with histories and findings consistent with brucellosis. CLs were not notified that specimens might yield a hazardous organism, as the clinicians did not consider brucellosis until they were notified that bacteremia with Brucella was suspected. In 3 Brucella events, the CLs did not suspect that slow-growing, small Gram-negative bacteria might be harmful. Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), which has a limited capacity to identify biological threat agents (BTAs), was used during 4 Brucella events, which accounted for 84% of exposures. In 3 of these incidents, initial staining of liquid media showed Gram-positive rods or cocci, including some cocci in chains, suggesting streptococci. Over 200 occupational exposures occurred when the unknown isolates were manipulated and/or tested on open benches, including by procedures that could generate infectious aerosols. During 3 Brucella events, the CLs examined and/or manipulated isolates in a biological safety cabinet (BSC); in each CL, the CL had previously isolated Brucella Centers for Disease Control and Prevention recommendations to prevent laboratory-acquired brucellosis (LAB) were followed; no seroconversions or LAB cases occurred. Laboratory assessments were conducted after the Brucella events to identify facility-specific risks and mitigations. With increasing MALDI-TOF MS use, CLs are well-advised to adhere strictly to safe work practices, such as handling and manipulating all slow-growing organisms in BSCs and not using MALDI-TOF MS for identification until BTAs have been ruled out.


Subject(s)
Brucella/isolation & purification , Brucellosis/diagnosis , Clinical Laboratory Techniques/standards , Laboratory Infection/microbiology , Occupational Exposure/statistics & numerical data , Brucella/growth & development , Brucellosis/etiology , Colony Count, Microbial , Humans , New York City , Occupational Exposure/prevention & control , Risk Factors , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
7.
Transpl Infect Dis ; 22(1): e13215, 2020 Feb.
Article in English | MEDLINE | ID: mdl-31765045

ABSTRACT

BACKGROUND: Infections secondary to multidrug-resistant organisms (MDRO) have emerged as a growing problem in solid organ transplantation (SOT). Most of the published data on MDRO infections in SOT pertains to abdominal organ transplantation and data specific to heart transplantation (HT) are limited. METHODS: This is a retrospective review of HT recipients at our institution from 2011 to 2016; with the aim to investigate the epidemiology, microbiologic spectrum, and outcomes in patients with post-HT MDRO infections, classified as multidrug-resistant (MDR), extensively drug-resistant (XDR), and pandrug-resistant (PDR) using standardized definitions. RESULTS: Of the 149 HT recipients, 82 episodes of bacterial infection were seen in 46 patients (31%) in the year following HT. Thirty (37%) were due to MDR pathogens and 13 (16%) were XDR. The most common gram-negative MDR pathogens were extended-spectrum beta-lactamase (ESBL) Escherichia coli and Klebsiella pneumoniae; while XDR pathogens were most commonly Pseudomonas aeruginosa followed by carbapenem-resistant Klebsiella pneumoniae. Majority of infection episodes were bloodstream (54, 66%) followed by pulmonary infection (20, 24%). Within a year after transplant, HT recipients with any bacterial infection had significantly higher mortality versus those without infection; and XDR infections were associated with a 26-fold greater hazard of death on average compared to those without infection (adjusted HR, 26.1; 95% CI, 6.4-107.0; P < .001). There were no PDR infections. CONCLUSION: Bacterial infections were a significant predictor of 1-year post-HT mortality, which was highest among those with XDR infections. This study highlights the burden of MDRO infections in HT recipients and identifies an area of future research.


Subject(s)
Bacteremia/mortality , Bacterial Infections/epidemiology , Drug Resistance, Multiple, Bacterial , Heart Transplantation/adverse effects , Adult , Aged , Anti-Bacterial Agents/therapeutic use , Bacteria/drug effects , Bacterial Infections/drug therapy , Bacterial Infections/mortality , Electronic Health Records , Female , Humans , Male , Middle Aged , New York City/epidemiology , Retrospective Studies
8.
J Clin Microbiol ; 57(12)2019 12.
Article in English | MEDLINE | ID: mdl-31578260

ABSTRACT

Whole-genome sequencing (WGS) of Staphylococcus aureus is increasingly used as part of infection prevention practices. In this study, we established a long-read technology-based WGS screening program of all first-episode methicillin-resistant Staphylococcus aureus (MRSA) blood infections at a major urban hospital. A survey of 132 MRSA genomes assembled from long reads enabled detailed characterization of an outbreak lasting several months of a CC5/ST105/USA100 clone among 18 infants in a neonatal intensive care unit (NICU). Available hospital-wide genome surveillance data traced the origins of the outbreak to three patients admitted to adult wards during a 4-month period preceding the NICU outbreak. The pattern of changes among complete outbreak genomes provided full spatiotemporal resolution of its progression, which was characterized by multiple subtransmissions and likely precipitated by equipment sharing between adults and infants. Compared to other hospital strains, the outbreak strain carried distinct mutations and accessory genetic elements that impacted genes with roles in metabolism, resistance, and persistence. This included a DNA recognition domain recombination in the hsdS gene of a type I restriction modification system that altered DNA methylation. Transcriptome sequencing (RNA-Seq) profiling showed that the (epi)genetic changes in the outbreak clone attenuated agr gene expression and upregulated genes involved in stress response and biofilm formation. Overall, our findings demonstrate the utility of long-read sequencing for hospital surveillance and for characterizing accessory genomic elements that may impact MRSA virulence and persistence.


Subject(s)
Bacteremia/epidemiology , Cross Infection/epidemiology , Disease Outbreaks , Methicillin-Resistant Staphylococcus aureus/isolation & purification , Molecular Epidemiology/methods , Staphylococcal Infections/epidemiology , Whole Genome Sequencing/methods , Adult , Bacteremia/microbiology , Bacteremia/transmission , Cross Infection/microbiology , Cross Infection/transmission , Disease Transmission, Infectious , Genotype , Hospitals , Humans , Infant , Infant, Newborn , Intensive Care Units, Neonatal , Mass Screening/methods , Methicillin-Resistant Staphylococcus aureus/classification , Methicillin-Resistant Staphylococcus aureus/genetics , Staphylococcal Infections/microbiology , Staphylococcal Infections/transmission
9.
Clin Transplant ; 33(9): e13594, 2019 09.
Article in English | MEDLINE | ID: mdl-31102483

ABSTRACT

These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention, and management of infections due to multidrug-resistant (MDR) Gram-negative bacilli in the pre- and post-transplant period. MDR Gram-negative bacilli, including carbapenem-resistant Enterobacteriaceae, MDR Pseudomonas aeruginosa, and carbapenem-resistant Acinetobacter baumannii, remain a threat to successful organ transplantation. Clinicians now have access to at least five novel agents with activity against some of these organisms, with others in the advanced stages of clinical development. No agent, however, provides universal and predictable activity against any of these pathogens, and very little is available to treat infections with MDR nonfermenting Gram-negative bacilli including A baumannii. Despite advances, empiric antibiotics should be tailored to local microbiology and targeted regimens should be tailored to susceptibilities. Source control remains an important part of the therapeutic armamentarium. Morbidity and mortality associated with infections due to MDR Gram-negative organisms remain unacceptably high. Heightened infection control and antimicrobial stewardship initiatives are needed to prevent these infections, curtail their transmission, and limit the evolution of MDR Gram-negative pathogens, especially in the setting of organ transplantation.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Drug Resistance, Multiple, Bacterial , Gram-Negative Bacteria/isolation & purification , Gram-Negative Bacterial Infections/diagnosis , Gram-Negative Bacterial Infections/drug therapy , Organ Transplantation/adverse effects , Practice Guidelines as Topic/standards , Gram-Negative Bacterial Infections/etiology , Humans , Societies, Medical , Transplant Recipients
10.
Curr Opin Organ Transplant ; 24(4): 497-503, 2019 08.
Article in English | MEDLINE | ID: mdl-31145159

ABSTRACT

PURPOSE OF REVIEW: To provide an update on the current landscape of antimicrobial stewardship in solid organ transplant (SOT) recipients. RECENT FINDINGS: Constructing personalized antimicrobial prescribing approaches to avoid untoward consequences of antimicrobials while improving outcomes is an emerging and critical aspect of transplant medicine. Stewardship activities encompassing the specialized interests of transplant patients and programs are evolving. New literature evaluating strategies to optimize antimicrobial agent selection, dosing, and duration have been published. Additionally, consensus guidance for certain infectious clinical syndromes is available and should inform institutional clinical practice guidelines. Novel metrics for stewardship-related outcomes in transplantation are desperately needed. Though exciting new molecular diagnostic technologies will likely be pivotal in the care of immunocompromised patients, optimal clinical adaptation and appropriate integration remains unclear. Important studies understanding the behaviors influencing antimicrobial prescribing in organizational transplant cultures are needed to optimize interventions. SUMMARY: Consequences of antimicrobial use, such as Clostridiodes difficile and infections with multidrug-resistant organisms disproportionately affect SOT recipients and are associated with poor allograft and patient outcomes. Application of ASP interventions tailored to SOT recipients is recommended though further studies are needed to provide guidance for best practice.


Subject(s)
Antimicrobial Stewardship/methods , Organ Transplantation/adverse effects , Humans , Organ Transplantation/methods
11.
Emerg Infect Dis ; 24(3): 584-587, 2018 03.
Article in English | MEDLINE | ID: mdl-29460760

ABSTRACT

In 2015, Clostridium difficile testing rates among 30 US community, multispecialty, and cancer hospitals were 14.0, 16.3, and 33.9/1,000 patient-days, respectively. Pooled hospital onset rates were 0.56, 0.84, and 1.57/1,000 patient-days, respectively. Higher testing rates may artificially inflate reported rates of C. difficile infection. C. difficile surveillance should consider testing frequency.


Subject(s)
Clostridioides difficile , Clostridium Infections/epidemiology , Clostridium Infections/microbiology , Health Status Disparities , Bacteriological Techniques , Clostridioides difficile/genetics , Clostridium Infections/diagnosis , Hospitalization , Hospitals , Humans , Nucleic Acid Amplification Techniques , Public Health Surveillance
12.
Liver Transpl ; 24(5): 616-622, 2018 05.
Article in English | MEDLINE | ID: mdl-29500912

ABSTRACT

Liver transplantation recipients (LTRs) who are seropositive for cytomegalovirus (CMV) (recipient seropositive [R+]) are at intermediate risk for CMV disease. A preventative strategy following transplant is considered standard of care. Current guidelines recommend high-dose valganciclovir (VGCV; 900 mg/day adjusted for renal function) for prophylaxis given limited data on the efficacy and safety of low-dose VGCV (450 mg/day adjusted for renal function). We describe our experience using low-dose VGCV prophylaxis for R+ LTRs at our institution. A single-center, retrospective study was conducted using a database of 364 LTRs over a 4-year period (2011-2014). Adult first-time R+ LTRs receiving low-dose VGCV prophylaxis were included. The primary endpoint was CMV disease at 1 year after transplant. Patients were compared with historical controls receiving high-dose VGCV prophylaxis. Secondary endpoints were biopsy-proven rejection and leukopenia on VGCV. With respect to leukopenia, patients receiving low-dose VGCV were compared with a group of D+R- patients from the database receiving high-dose VGCV. Univariate analyses were performed using chi-squared, Fisher's exact, and Wilcoxon rank sum tests. A total of 200 R+ LTRs met inclusion criteria. Median age was 60 years (interquartile range [IQR], 54-66 years), and 129 (65%) LTRs were male. Median Model for End-Stage Liver Disease score was 22 (IQR, 14-31), and 178 (89%) patients received deceased donor transplants. CMV disease occurred in only 9 (5%) patients, similar to rates in previous studies of LTRs receiving high-dose VGCV. Biopsy-proven rejection occurred in 18 (9%) patients. Patients received VGCV prophylaxis for a median of 3.4 (IQR, 3.1-4.3) months; 151 (76%) R+ LTRs receiving low-dose VGCV developed leukopenia. Premature VGCV discontinuation and granulocyte-colony stimulating factor use were infrequent and not significantly different between the 2 groups. In conclusion, low-dose VGCV was safe and effective for prevention of CMV disease in our cohort of 200 R+ LTR and should be considered as an option in future guidelines. Liver Transplantation 24 616-622 2018 AASLD.


Subject(s)
Antiviral Agents/administration & dosage , Cytomegalovirus Infections/prevention & control , Ganciclovir/analogs & derivatives , Liver Transplantation/adverse effects , Opportunistic Infections/prevention & control , Aged , Antiviral Agents/adverse effects , Chi-Square Distribution , Cytomegalovirus Infections/diagnosis , Cytomegalovirus Infections/immunology , Cytomegalovirus Infections/virology , Databases, Factual , Female , Ganciclovir/administration & dosage , Ganciclovir/adverse effects , Graft Rejection/immunology , Graft Rejection/prevention & control , Humans , Immunocompromised Host , Immunosuppressive Agents/adverse effects , Leukopenia/chemically induced , Male , Middle Aged , New York City , Opportunistic Infections/diagnosis , Opportunistic Infections/immunology , Opportunistic Infections/virology , Retrospective Studies , Risk Factors , Time Factors , Treatment Outcome , Valganciclovir
13.
Transpl Infect Dis ; 20(1)2018 Feb.
Article in English | MEDLINE | ID: mdl-29139180

ABSTRACT

BACKGROUND: An active bloodstream infection (BSI) is typically considered a contraindication to heart transplantation (HT). However, in some patients with Staphylococcus bacteremia and mechanical circulatory support device infection, positive blood cultures may persist until removal of the infected device, and eradicating the infection prior to HT may not be possible. We report the outcomes of six patients with active Staphylococcus BSI at the time of HT. METHODS: All cases of HT performed at The Mount Sinai Hospital from 2009 through 2015 were reviewed. All patients with a mechanical circulatory support device and an active Staphylococcus BSI at the time of HT were included. RESULTS: Six patients with active Staphylococcus bacteremia and suspected mechanical circulatory support device infection underwent HT. All patients were bacteremic with Staphylococcus species at the time of HT. All were managed with antimicrobial therapy, radical debridement at the time of HT, and limited use of immunosuppression, and all survived until hospital discharge with no evidence of relapsed Staphylococcus infection. CONCLUSION: These results suggest that some carefully selected patients with active Staphylococcus bacteremia and suspected mechanical circulatory support device infection may safely undergo HT, and that HT may effectively eliminate the underlying infection.


Subject(s)
Bacteremia/microbiology , Catheter-Related Infections/microbiology , Heart Transplantation , Heart-Assist Devices/microbiology , Staphylococcal Infections/blood , Staphylococcus/isolation & purification , Adult , Anti-Bacterial Agents/therapeutic use , Bacteremia/drug therapy , Female , Heart-Assist Devices/adverse effects , Humans , Male , Middle Aged , Staphylococcal Infections/drug therapy , Staphylococcus/drug effects
14.
Transpl Infect Dis ; 20(1)2018 Feb.
Article in English | MEDLINE | ID: mdl-29110413

ABSTRACT

BACKGROUND: Data are limited on clinical outcomes in patients awaiting heart transplant (HT) with total artificial heart (TAH) infections. METHODS: We retrospectively reviewed all TAH recipients at our center. TAH infection was classified as definite if a microorganism was isolated in cultures from the exit site or deep tissues around the TAH; as probable in patients without surgical or microbiologic evidence of infection but no other explanation for persistent or recurrent bloodstream infection (BSI); or possible in patients with clinical suspicion and radiographic findings suggestive of TAH infection, but without surgical intervention or microbiologic evidence. RESULTS: From 2012 to 2015, a total of 13 patients received a TAH, with a median age at implantation of 52 years (range: 28-60). TAH infection occurred in nine patients (seven definite, one probable, one possible) a median of 41 days after implant (range: 17-475). The majority of TAH infections were caused by Staphylococcus species. Seven of nine patients underwent HT (four had pre-HT mediastinal washout, and five had positive HT operative cultures). Three patients had an active BSI caused by the same pathogen causing TAH infection at the time of HT, with one developing a post-HT BSI with the same bacteria. No patient developed post-HT surgical site infection caused by the TAH infection pathogen. No deaths among HT recipients were attributed to infection. CONCLUSION: TAH infection is frequently associated with BSI and mediastinitis and Staphylococcus was the most common pathogen. A multimodal approach of appropriate pre- and post-HT antimicrobial therapy, surgical drainage, and heart transplantation with radical mediastinal debridement was successful in curing infection.


Subject(s)
Heart Transplantation/adverse effects , Heart, Artificial/microbiology , Patient Outcome Assessment , Surgical Wound Infection/microbiology , Adult , Debridement , Female , Heart Failure/prevention & control , Heart Transplantation/statistics & numerical data , Heart, Artificial/statistics & numerical data , Humans , Male , Mediastinitis/epidemiology , Mediastinitis/microbiology , Middle Aged , Retrospective Studies , Staphylococcal Infections/blood , Staphylococcal Infections/epidemiology , Staphylococcal Infections/microbiology , Staphylococcus/isolation & purification , Surgical Wound Infection/epidemiology , Time Factors
15.
Article in English | MEDLINE | ID: mdl-28167547

ABSTRACT

Although the New York/New Jersey (NY/NJ) area is an epicenter for carbapenem-resistant Enterobacteriaceae (CRE), there are few multicenter studies of CRE from this region. We characterized patients with CRE bacteremia in 2013 at eight NY/NJ medical centers and determined the prevalence of carbapenem resistance among Enterobacteriaceae bloodstream isolates and CRE resistance mechanisms, genetic backgrounds, capsular types (cps), and antimicrobial susceptibilities. Of 121 patients with CRE bacteremia, 50% had cancer or had undergone transplantation. The prevalences of carbapenem resistance among Klebsiella pneumoniae, Enterobacter spp., and Escherichia coli bacteremias were 9.7%, 2.2%, and 0.1%, respectively. Ninety percent of CRE were K. pneumoniae and 92% produced K. pneumoniae carbapenemase (KPC-3, 48%; KPC-2, 44%). Two CRE produced NDM-1 and OXA-48 carbapenemases. Sequence type 258 (ST258) predominated among KPC-producing K. pneumoniae (KPC-Kp). The wzi154 allele, corresponding to cps-2, was present in 93% of KPC-3-Kp, whereas KPC-2-Kp had greater cps diversity. Ninety-nine percent of CRE were ceftazidime-avibactam (CAZ-AVI)-susceptible, although 42% of KPC-3-Kp had an CAZ-AVI MIC of ≥4/4 µg/ml. There was a median of 47 h from bacteremia onset until active antimicrobial therapy, 38% of patients had septic shock, and 49% died within 30 days. KPC-3-Kp bacteremia (adjusted odds ratio [aOR], 2.58; P = 0.045), cancer (aOR, 3.61, P = 0.01), and bacteremia onset in the intensive care unit (aOR, 3.79; P = 0.03) were independently associated with mortality. Active empirical therapy and combination therapy were not associated with survival. Despite a decade of experience with CRE, patients with CRE bacteremia have protracted delays in appropriate therapies and high mortality rates, highlighting the need for rapid diagnostics and evaluation of new therapeutics.


Subject(s)
Anti-Bacterial Agents/pharmacology , Bacteremia/microbiology , Carbapenems/pharmacology , Enterobacteriaceae/drug effects , Enterobacter/drug effects , Enterobacter/genetics , Enterobacter/metabolism , Enterobacteriaceae/genetics , Enterobacteriaceae/metabolism , Escherichia coli/drug effects , Escherichia coli/genetics , Escherichia coli/metabolism , Humans , Klebsiella pneumoniae/drug effects , Klebsiella pneumoniae/genetics , Klebsiella pneumoniae/metabolism , Microbial Sensitivity Tests , Molecular Epidemiology
16.
PLoS Pathog ; 11(3): e1004770, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25822986

ABSTRACT

Imatinib mesylate (Gleevec) inhibits Abl1, c-Kit, and related protein tyrosine kinases (PTKs) and serves as a therapeutic for chronic myelogenous leukemia and gastrointestinal stromal tumors. Imatinib also has efficacy against various pathogens, including pathogenic mycobacteria, where it decreases bacterial load in mice, albeit at doses below those used for treating cancer. We report that imatinib at such low doses unexpectedly induces differentiation of hematopoietic stem cells and progenitors in the bone marrow, augments myelopoiesis but not lymphopoiesis, and increases numbers of myeloid cells in blood and spleen. Whereas progenitor differentiation relies on partial inhibition of c-Kit by imatinib, lineage commitment depends upon inhibition of other PTKs. Thus, imatinib mimics "emergency hematopoiesis," a physiological innate immune response to infection. Increasing neutrophil numbers by adoptive transfer sufficed to reduce mycobacterial load, and imatinib reduced bacterial load of Franciscella spp., which do not utilize imatinib-sensitive PTKs for pathogenesis. Thus, potentiation of the immune response by imatinib at low doses may facilitate clearance of diverse microbial pathogens.


Subject(s)
Cell Differentiation/drug effects , Francisella/immunology , Gram-Negative Bacterial Infections/immunology , Imatinib Mesylate/pharmacology , Myelopoiesis/drug effects , Neutrophils/immunology , Animals , Cell Differentiation/immunology , Leukocyte Count , Mice , Myelopoiesis/immunology
17.
Liver Transpl ; 22(8): 1143-53, 2016 08.
Article in English | MEDLINE | ID: mdl-27228555

ABSTRACT

Liver transplant (LT) recipients are vulnerable to infections with multidrug-resistant (MDR) pathogens. Risk factors for colonization and infection with resistant bacteria are ubiquitous and unavoidable in transplantation. During the past decade, progress in transplantation and infection prevention has contributed to the decreased incidence of infections with methicillin-resistant Staphylococcus aureus. However, even in the face of potentially effective antibiotics, vancomycin-resistant enterococci continue to plague LT. Gram-negative bacilli prove to be more problematic and are responsible for high rates of both morbidity and mortality. Despite the licensure of novel antibiotics, there is no universal agent available to safely and effectively treat infections with MDR gram-negative organisms. Currently, efforts dedicated toward prevention and treatment require involvement of multiple disciplines including transplant providers, specialists in infectious diseases and infection prevention, and researchers dedicated to the development of rapid diagnostics and safe and effective antibiotics with novel mechanisms of action. Liver Transplantation 22 1143-1153 2016 AASLD.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Drug Resistance, Multiple, Bacterial , Gram-Negative Bacteria/physiology , Gram-Negative Bacterial Infections/drug therapy , Gram-Positive Bacteria/physiology , Gram-Positive Bacterial Infections/drug therapy , Liver Transplantation/adverse effects , Anti-Bacterial Agents/administration & dosage , Catheter-Related Infections/drug therapy , Catheter-Related Infections/prevention & control , Cross Infection/drug therapy , Cross Infection/prevention & control , Disease Transmission, Infectious/prevention & control , Drug Therapy, Combination , Gram-Negative Bacteria/isolation & purification , Gram-Negative Bacterial Infections/epidemiology , Gram-Negative Bacterial Infections/microbiology , Gram-Negative Bacterial Infections/prevention & control , Gram-Positive Bacteria/isolation & purification , Gram-Positive Bacterial Infections/epidemiology , Gram-Positive Bacterial Infections/microbiology , Gram-Positive Bacterial Infections/prevention & control , Humans , Incidence , Risk Factors
18.
MMWR Morb Mortal Wkly Rep ; 65(44): 1234-1237, 2016 Nov 11.
Article in English | MEDLINE | ID: mdl-27832049

ABSTRACT

Candida auris, an emerging fungus that can cause invasive infections, is associated with high mortality and is often resistant to multiple antifungal drugs. C. auris was first described in 2009 after being isolated from external ear canal discharge of a patient in Japan (1). Since then, reports of C. auris infections, including bloodstream infections, have been published from several countries, including Colombia, India, Israel, Kenya, Kuwait, Pakistan, South Africa, South Korea, Venezuela, and the United Kingdom (2-7). To determine whether C. auris is present in the United States and to prepare for the possibility of transmission, CDC issued a clinical alert in June 2016 informing clinicians, laboratorians, infection control practitioners, and public health authorities about C. auris and requesting that C. auris cases be reported to state and local health departments and CDC (8). This report describes the first seven U.S. cases of C. auris infection reported to CDC as of August 31, 2016. Data from these cases suggest that transmission of C. auris might have occurred in U.S. health care facilities and demonstrate the need for attention to infection control measures to control the spread of this pathogen.


Subject(s)
Candida/isolation & purification , Candidiasis/diagnosis , Candidiasis/microbiology , Antifungal Agents/pharmacology , Antifungal Agents/therapeutic use , Candida/drug effects , Candidiasis/drug therapy , Communicable Diseases, Emerging , Drug Resistance, Multiple, Fungal , Fatal Outcome , Global Health , Humans , United States
19.
Antimicrob Agents Chemother ; 59(11): 7117-20, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26324280

ABSTRACT

Whole-genome sequences for Stenotrophomonas maltophilia serial isolates from a bacteremic patient before and after development of levofloxacin resistance were assembled de novo and differed by one single-nucleotide variant in smeT, a repressor for multidrug efflux operon smeDEF. Along with sequenced isolates from five contemporaneous cases, they displayed considerable diversity compared against all published complete genomes. Whole-genome sequencing and complete assembly can conclusively identify resistance mechanisms emerging in S. maltophilia strains during clinical therapy.


Subject(s)
Genome, Bacterial/genetics , Gram-Negative Bacterial Infections/microbiology , Quinolones/pharmacology , Stenotrophomonas maltophilia/immunology , DNA, Bacterial/genetics , Drug Resistance, Multiple, Bacterial/genetics , Microbial Sensitivity Tests , Mutation
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