Shirish Huprikar

Outcomes of Carbapenem‐Resistant Klebsiella pneumoniae Infection and the Impact of Antimicrobial and Adjunctive Therapies

BACKGROUND Carbapenem-resistant Klebsiella pneumoniae is an emerging healthcare-associated pathogen. OBJECTIVE To describe the epidemiology of and clinical outcomes associated with carbapenem-resistant K. pneumoniae infection and to identify risk factors associated with mortality among patients with this type of infection. SETTING Mount Sinai Hospital, a 1,171-bed tertiary care teaching hospital in New York City. DESIGN Two matched case-control studies. METHODS In the first matched case-control study, case patients with carbapenem-resistant K. pneumoniae infection were compared with control patients with carbapenem-susceptible K. pneumoniae infection. In the second case-control study, patients who survived carbapenem-resistant K. pneumoniae infection were compared with those who did not survive, to identify risk factors associated with mortality among patients with carbapenem-resistant K. pneumoniae infection. RESULTS There were 99 case patients and 99 control patients identified. Carbapenem-resistant K. pneumoniae infection was independently associated with recent organ or stem-cell transplantation (P=.008), receipt of mechanical ventilation (P=.04), longer length of stay before infection (P=.01), and exposure to cephalosporins (P=.02) and carbapenems (P<.001). Case patients were more likely than control patients to die during hospitalization (48% vs 20%; P<.001) and to die from infection (38% vs 12%; P<.001). Removal of the focus of infection (ie, debridement) was independently associated with patient survival (P=.002). The timely administration of antibiotics with in vitro activity against carbapenem-resistant K. pneumoniae was not associated with patient survival. CONCLUSIONS Carbapenem-resistant K. pneumoniae infection is associated with numerous healthcare-related risk factors and with high mortality. The mortality rate associated with carbapenem-resistant K. pneumoniae infection and the limited antimicrobial options for treatment of carbapenem-resistant K. pneumoniae infection highlight the need for improved detection of carbapenem-resistant K. pneumoniae infection, identification of effective preventive measures, and development of novel agents with reliable clinical efficacy against carbapenem-resistant K. pneumoniae.

Outcomes from pandemic influenza A H1N1 infection in recipients of solid-organ transplants: a multicentre cohort study

BACKGROUND There are few data on the epidemiology and outcomes of influenza infection in recipients of solid-organ transplants. We aimed to establish the outcomes of pandemic influenza A H1N1 and factors leading to severe disease in a cohort of patients who had received transplants. METHODS We did a multicentre cohort study of adults and children who had received organ transplants with microbiological confirmation of influenza A infection from April to December, 2009. Centres were identified through the American Society of Transplantation Influenza Collaborative Study Group. Demographics, clinical presentation, treatment, and outcomes were assessed. Severity of disease was measured by admission to hospital and intensive care units (ICUs). The data were analysed with descriptive statistics. Proportions were compared by use of chi(2) tests. We used univariate analysis to identify factors leading to pneumonia, admission to hospital, and admission to an ICU. Multivariate analysis was done by use of a stepwise logistic regression model. We analysed deaths with Kaplan-Meier survival analysis. FINDINGS We assessed 237 cases of medically attended influenza A H1N1 reported from 26 transplant centres during the study period. Transplant types included kidney, liver, heart, lung, and others. Both adults (154 patients; median age 47 years) and children (83; 9 years) were assessed. Median time from transplant was 3.6 years. 167 (71%) of 237 patients were admitted to hospital. Data on complications were available for 230 patients; 73 (32%) had pneumonia, 37 (16%) were admitted to ICUs, and ten (4%) died. Antiviral treatment was used in 223 (94%) patients (primarily oseltamivir monotherapy). Seven (8%) patients given antiviral drugs within 48 h of symptom onset were admitted to an ICU compared with 28 (22.4%) given antivirals later (p=0.007). Children who received transplants were less likely to present with pneumonia than adults, but rates of admission to hospital and ICU were similar. INTERPRETATION Influenza A H1N1 caused substantial morbidity in recipients of solid-organ transplants during the 2009-10 pandemic. Starting antiviral therapy early is associated with clinical benefit as measured by need for ICU admission and mechanical ventilation. FUNDING None.

Mortality associated with carbapenem-resistant Klebsiella pneumoniae infections in liver transplant recipients.

Resistant bacterial infections are important causes of morbidity and mortality after liver transplantation (LT). This was a retrospective cohort study evaluating the outcomes associated with carbapenem‐resistant Klebsiella pneumoniae (CRKP) infections after LT. In a 2005‐2006 cohort of 175 consecutive LT recipients, 91 infection episodes were observed in 61 patients (35%). The mortality rate 1 year after LT was 18% (32/175). Enterococcus (43%) and Klebsiella species (37%) were the most frequently isolated bacteria. CRKP infections occurred in 14 patients, and 10 of these patients (71%) died. Seven of these deaths occurred within 30 days of the CRKP infection. The median time to the onset of CRKP infections was 12 days (range = 1‐126 days) after LT. The survival rate was significantly lower for patients with a CRKP infection versus patients without a CRKP infection (29% versus 86%, log‐rank P < 0.001). In a multivariate analysis, the only pre‐LT and post‐LT clinical variables significantly associated with death were a Model for End‐Stage Liver Disease score ≥ 30 (hazard ratio = 3.4, P = 0.04) and a post‐LT CRKP infection (hazard ratio = 4.9, P = 0.007). In conclusion, the outcomes associated with CRKP infections in LT recipients are poor. Because the optimal treatment strategies for CRKP infections remain undefined, improved preventive strategies are needed to curtail the devastating impact of CRKP in LT recipients. Liver Transpl 18:468–474, 2012.

Donor-Derived Fungal Infections in Organ Transplant Recipients: Guidelines of the American Society of Transplantation, Infectious Diseases Community of Practice†

Donor‐derived fungal infections can be associated with serious complications in transplant recipients. Most cases of donor‐derived candidiasis have occurred in kidney transplant recipients in whom contaminated preservation fluid is a commonly proposed source. Donors with cryptococcal disease, including those with unrecognized cryptococcal meningoencephalitis may transmit the infection with the allograft. Active histoplasmosis or undiagnosed and presumably asymptomatic infection in the donor that had not resolved by the time of death can result in donor‐derived histoplasmosis in the recipient. Potential donors from an endemic area with either active or occult infection can also transmit coccidioidomycosis. Rare instances of aspergillosis and other mycoses, including agents of mucormycosis may also be transmitted from infected donors. Appropriate diagnostic evaluation and prompt initiation of appropriate antifungal therapy are warranted if donor‐derived fungal infections are a consideration. This document discusses the characteristics, evaluation and approach to the management of donor‐derived fungal infections in organ transplant recipients.

Histoplasmosis After Solid Organ Transplant

BACKGROUND To improve our understanding of risk factors, management, diagnosis, and outcomes associated with histoplasmosis after solid organ transplant (SOT), we report a large series of histoplasmosis occurring after SOT. METHODS All cases of histoplasmosis in SOT recipients diagnosed between 1 January 2003 and 31 December 2010 at 24 institutions were identified. Demographic, clinical, and laboratory data were collected. RESULTS One hundred fifty-two cases were identified: kidney (51%), liver (16%), kidney/pancreas (14%), heart (9%), lung (5%), pancreas (2%), and other (2%). The median time from transplant to diagnosis was 27 months, but 34% were diagnosed in the first year after transplant. Twenty-eight percent of patients had severe disease (requiring intensive care unit admission); 81% had disseminated disease. Urine Histoplasma antigen detection was the most sensitive diagnostic method, positive in 132 of 142 patients (93%). An amphotericin formulation was administered initially to 73% of patients for a median duration of 2 weeks; step-down therapy with an azole was continued for a median duration of 12 months. Ten percent of patients died due to histoplasmosis with 72% of deaths occurring in the first month after diagnosis; older age and severe disease were risk factors for death from histoplasmosis. Relapse occurred in 6% of patients. CONCLUSIONS Although late cases occur, the first year after SOT is the period of highest risk for histoplasmosis. In patients who survive the first month after diagnosis, treatment with an amphotericin formulation followed by an azole for 12 months is usually successful, with only rare relapse.

Telaprevir in the Treatment of Acute Hepatitis C Virus Infection in HIV-Infected Men

BACKGROUND There is an international epidemic of hepatitis C virus (HCV) infection among human immunodeficiency virus (HIV)-infected men who have sex with men. Sustained virologic response (SVR) rates with pegylated interferon and ribavirin treatment are higher in these men during acute HCV than during chronic HCV, but treatment is still lengthy and SVR rates are suboptimal. METHODS We performed a pilot study of combination therapy with telaprevir, pegylated interferon, and ribavirin in acute genotype 1 HCV infection in HIV-infected men. Men who were treated prior to the availability of, or ineligible for, telaprevir were the comparator group. The primary endpoint was SVR12, defined as an HCV viral load <5 IU/mL at least 12 weeks after completing treatment. RESULTS In the telaprevir group, 84% (16/19) of men achieved SVR12 vs 63% (30/48) in the comparator group. Among men with SVR, median time to undetectable viral load was week 2 in the telaprevir group vs week 4 in the comparator group, and 94% vs 53% had undetectable viral loads at week 4. Most patients (81%) who achieved SVR in the telaprevir group received ≤12 weeks of treatment and there were no relapses after treatment. The overall safety profile was similar to that known for telaprevir-based regimens. CONCLUSIONS Incorporating telaprevir into treatment of acute genotype 1 HCV in HIV-infected men halved the treatment duration and increased the SVR rate. Larger studies should be done to confirm these findings. Clinicians should be alert to detect acute HCV infection of HIV-infected men to take advantage of this effective therapy and decrease further transmission in this epidemic.

MELD Score Is an Important Predictor of Pretransplantation Mortality in HIV-Infected Liver Transplant Candidates

BACKGROUND & AIMS Human immunodeficiency virus (HIV) infection accelerates liver disease progression in patients with hepatitis C virus (HCV) and could shorten survival of those awaiting liver transplants. The Model for End-Stage Liver Disease (MELD) score predicts mortality in HIV-negative transplant candidates, but its reliability has not been established in HIV-positive candidates. METHODS We evaluated predictors of pretransplantation mortality in HIV-positive liver transplant candidates enrolled in the Solid Organ Transplantation in HIV: Multi-Site Study (HIVTR) matched 1:5 by age, sex, race, and HCV infection with HIV-negative controls from the United Network for Organ Sharing. RESULTS Of 167 HIVTR candidates, 24 died (14.4%); this mortality rate was similar to that of controls (88/792, 11.1%, P = .30) with no significant difference in causes of mortality. A significantly lower proportion of HIVTR candidates (34.7%) underwent liver transplantation, compared with controls (47.6%, P = .003). In the combined cohort, baseline MELD score predicted pretransplantation mortality (hazard ratio [HR], 1.27; P < .0001), whereas HIV infection did not (HR, 1.69; P = .20). After controlling for pretransplantation CD4(+) cell count and HIV RNA levels, the only significant predictor of mortality in the HIV-infected subjects was pretransplantation MELD score (HR, 1.2; P < .0001). CONCLUSIONS Pretransplantation mortality characteristics are similar between HIV-positive and HIV-negative candidates. Although lower CD4(+) cell counts and detectable levels of HIV RNA might be associated with a higher rate of pretransplantation mortality, baseline MELD score was the only significant independent predictor of pretransplantation mortality in HIV-infected liver transplant candidates.

Strongyloides hyperinfection syndrome after intestinal transplantation

Abstract: Strongyloides stercoralis is a helminth with the ability to autoinfect the human host and persist asymptomatically for several years. Immunosuppression can accelerate autoinfection and result in Strongyloides hyperinfection syndrome (SHS), which is associated with significant morbidity and mortality. Immunosuppressed solid organ transplant recipients, particularly in the setting of rejection, are at increased risk for reactivation of latent infections, such as Strongyloides. We describe a case of SHS in an intestinal transplant recipient; we hypothesize that she acquired the infection from the donor. We also review the current literature and address both prophylaxis and treatment of strongyloidiasis in the solid organ transplant patient.

Solid Organ Transplantation From Hepatitis B Virus–Positive Donors: Consensus Guidelines for Recipient Management

Use of organs from donors testing positive for hepatitis B virus (HBV) may safely expand the donor pool. The American Society of Transplantation convened a multidisciplinary expert panel that reviewed the existing literature and developed consensus recommendations for recipient management following the use of organs from HBV positive donors. Transmission risk is highest with liver donors and significantly lower with non‐liver (kidney and thoracic) donors. Antiviral prophylaxis significantly reduces the rate of transmission to liver recipients from isolated HBV core antibody positive (anti‐HBc+) donors. Organs from anti‐HBc+ donors should be considered for all adult transplant candidates after an individualized assessment of the risks and benefits and appropriate patient consent. Indefinite antiviral prophylaxis is recommended in liver recipients with no immunity or vaccine immunity but not in liver recipients with natural immunity. Antiviral prophylaxis may be considered for up to 1 year in susceptible non‐liver recipients but is not recommended in immune non‐liver recipients. Although no longer the treatment of choice in patients with chronic HBV, lamivudine remains the most cost‐effective choice for prophylaxis in this setting. Hepatitis B immunoglobulin is not recommended.

Unrecognized pretransplant and donor derived cryptococcal disease in organ transplant recipients.

BACKGROUND Cryptococcosis occurring ≤30 days after transplantation is an unusual event, and its characteristics are not known. METHODS Patients included 175 solid-organ transplant (SOT) recipients with cryptococcosis in a multicenter cohort. Very early-onset and late-onset cryptococcosis were defined as disease occurring ≤30 days or >30 days after transplantation, respectively. RESULTS Very early-onset disease developed in 9 (5%) of the 175 patients at a mean of 5.7 days after transplantation. Overall, 55.6% (5 of 9) of the patients with very early-onset disease versus 25.9% (43 of 166) of the patients with late-onset disease were liver transplant recipients (P = .05). Very early cases were more likely to present with disease at unusual locations, including transplanted allograft and surgical fossa/site infections (55.6% vs 7.2%; P < .001). Two very early cases with onset on day 1 after transplantation (in a liver transplant recipient with Cryptococcus isolated from the lung and a heart transplant recipient with fungemia) likely were the result of undetected pretransplant disease. An additional 5 cases involving the allograft or surgical sites were likely the result of donor‐acquired infection. CONCLUSIONS A subset of SOT recipients with cryptococcosis present very early after transplantation with disease that appears to occur preferentially in liver transplant recipients and involves unusual sites, such as the transplanted organ or the surgical site. These patients may have unrecognized pretransplant or donor-derived cryptococcosis.