Gail E. Reid

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.

Rapid development of Acinetobacter baumannii resistance to tigecycline

A 53‐year‐old woman experienced a multidrug‐resistant (MDR) Acinetobacter baumannii urinary tract infection 5 months after undergoing kidney and liver transplantation. The tigecycline minimum inhibitory concentration (MIC) for her A. baumannii isolate was 1.5 μg/ml; the patient received 2 weeks of therapy with intravenous tigecycline as a 100‐mg loading dose followed by 50 mg every 12 hours, with no lapses in treatment and with resolution of the infection. Three weeks later, MDR A. baumannii was isolated from her sputum in the setting of clinical evidence of pneumonia, and tigecycline was restarted; the tigecycline MIC for the A. baumannii isolate was 2 μg/ml. At approximately the same time, the patient was found to have a paraspinal abscess and spinal osteomyelitis. Cultures of the abscess fluid grew A. baumannii with a tigecycline MIC of 24 μg/ml. A follow‐up sputum culture again yielded A. baumannii, but with a tigecycline MIC of 24 μg/ml. Urine culture at that time also grew A. baumannii with a tigecycline MIC of 24 μg/ml. Clinicians should be aware that tigecycline MICs for A. baumannii isolates may increase during therapy with tigecycline after only brief exposure to the drug. Patients receiving tigecycline for Acinetobacter should be monitored for the development of clinical resistance, and isolates should be monitored for evidence of microbiologic resistance.

Nocardia infections in solid organ transplantation.

Nocardia species are ubiquitous saprophytic gram-positive bacteria in the ‘aerobic actinomycetes’ group (1), which also includes Corynebacterium, Rhodococcus, Gordonia, Tsukamurella, Actinomadura and Mycobacterium (2–4). More than 30 of the 80 Nocardia species characterized have been associated with disease (2,5,6). The most important causes of infection in transplant recipients are Nocardia asteroides sensu stricto (1), N. farcinica, N. nova, N. brasiliensis, N. otitidiscaviarum and the N. transvalensis complex (4,6–9). Molecular methods have now identified many new species which cause infection (2,6,10), including N. veterana (11), N. abscessus (12), N. paucivorans (13), and N. wallacei and N. blacklockiae of the N. transvalensis complex (9). Nocardia cyriacigeorgica is becoming a commonly identified human pathogen (2,5,14–19). From 1995 to 2004, the most common Nocardia species of 765 United States (US) isolates were N. nova (28%), N. brasiliensis (14%), N. farcinica (14%) and N. cyriacigeorgica (13%) (19).

Early Intra-Abdominal Infections Associated With Orthotopic Liver Transplantation

Background. Postoperative infections remain a significant problem among liver transplant recipients (LTRs). An early cause of morbidity after liver transplantation is intra-abdominal infection (IAI) about which there are limited data. Methods. We report a retrospective review of 169 adult LTRs from January 1, 2002 to June 9, 2006, comparing those who developed early postoperative IAI (peritonitis, biliary tract infection, abdominal abscess, or enteritis) with those who did not to identify clinical features and risk factors, analyze epidemiology, and assess graft and patient survival. Results. Sixty-eight patients (40%) had 104 infections, with 148 pathogens isolated. Leukocytosis (53%) and fever (34%) were the most common clinical features, and peritonitis (43%) was the most common manifestation. Enterococcus spp., the most frequent single pathogens, comprised 26% of organisms cultured. There were significant associations of IAI with pretransplant ascites (P=0.002), posttransplant dialysis (P=0.015), and non-IAI surgical complications (P<0.001). There was a trend toward graft failure in patients with IAI (P=0.051) but increased mortality was not associated with IAI. Use of pretransplant antibiotics was significantly associated with development of multiple drug–resistant organisms in IAI (P=0.032). Conclusion. IAI occurred at a relatively high rate in the early postoperative period, and fever was not a major indicator. In patients receiving antibiotics within 2 weeks before transplantation, multiple drug–resistant organisms often caused IAI. In addition, the presence of pretransplant ascites, posttransplant dialysis, and wound infection or reoperation after transplant should alert one to the increased risk of IAI in LTRs.

Severe influenza in 33 US hospitals, 2013–2014: Complications and risk factors for death in 507 patients

BACKGROUND Influenza A (H1N1) pdm09 became the predominant circulating strain in the United States during the 2013-2014 influenza season. Little is known about the epidemiology of severe influenza during this season. METHODS A retrospective cohort study of severely ill patients with influenza infection in intensive care units in 33 US hospitals from September 1, 2013, through April 1, 2014, was conducted to determine risk factors for mortality present on intensive care unit admission and to describe patient characteristics, spectrum of disease, management, and outcomes. RESULTS A total of 444 adults and 63 children were admitted to an intensive care unit in a study hospital; 93 adults (20.9%) and 4 children (6.3%) died. By logistic regression analysis, the following factors were significantly associated with mortality among adult patients: older age (>65 years, odds ratio, 3.1 [95% CI, 1.4-6.9], P=.006 and 50-64 years, 2.5 [1.3-4.9], P=.007; reference age 18-49 years), male sex (1.9 [1.1-3.3], P=.031), history of malignant tumor with chemotherapy administered within the prior 6 months (12.1 [3.9-37.0], P<.001), and a higher Sequential Organ Failure Assessment score (for each increase by 1 in score, 1.3 [1.2-1.4], P<.001). CONCLUSION Risk factors for death among US patients with severe influenza during the 2013-2014 season, when influenza A (H1N1) pdm09 was the predominant circulating strain type, shifted in the first postpandemic season in which it predominated toward those of a more typical epidemic influenza season.

Bacterial and viral co-infections complicating severe influenza: Incidence and impact among 507 U.S. patients, 2013–14

Abstract Background Influenza acts synergistically with bacterial co-pathogens. Few studies have described co-infection in a large cohort with severe influenza infection. Objectives To describe the spectrum and clinical impact of co-infections. Study design Retrospective cohort study of patients with severe influenza infection from September 2013 through April 2014 in intensive care units at 33 U.S. hospitals comparing characteristics of cases with and without co-infection in bivariable and multivariable analysis. Results Of 507 adult and pediatric patients, 114 (22.5%) developed bacterial co-infection and 23 (4.5%) developed viral co-infection. Staphylococcus aureus was the most common cause of co-infection, isolated in 47 (9.3%) patients. Characteristics independently associated with the development of bacterial co-infection of adult patients in a logistic regression model included the absence of cardiovascular disease (OR 0.41 [0.23–0.73], p=0.003), leukocytosis (>11K/μl, OR 3.7 [2.2–6.2], p<0.001; reference: normal WBC 3.5–11K/μl) at ICU admission and a higher ICU admission SOFA score (for each increase by 1 in SOFA score, OR 1.1 [1.0–1.2], p=0.001). Bacterial co-infections (OR 2.2 [1.4–3.6], p=0.001) and viral co-infections (OR 3.1 [1.3–7.4], p=0.010) were both associated with death in bivariable analysis. Patients with a bacterial co-infection had a longer hospital stay, a longer ICU stay and were likely to have had a greater delay in the initiation of antiviral administration than patients without co-infection (p<0.05) in bivariable analysis. Conclusions Bacterial co-infections were common, resulted in delay of antiviral therapy and were associated with increased resource allocation and higher mortality.

A multicenter evaluation of pandemic influenza A/H1N1 in hematopoietic stem cell transplant recipients

Hematopoietic stem cell transplant (HSCT) recipients have increased morbidity from respiratory viral infections. Pandemic influenza A – A(H1N1)/pdm09 – in 2009–2010 was associated with increased severity of illness in patients with underlying co‐morbidities including HSCT, but the factors that contribute to severe disease in HSCT patients are not well characterized.

Acinetobacter baumannii infection in solid organ transplant recipients

Acinetobacter baumannii can cause serious infection in susceptible patients, but little has been published regarding risk factors for infection and outcomes in solid organ transplant (SOT) recipients.

The use of fosfomycin to treat urinary tract infections in kidney transplant recipients.

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Treatment of MDR urinary tract infections with oral fosfomycin: a retrospective analysis

OBJECTIVES Limited options for treating MDR organisms have led clinicians to turn to older antimicrobial agents that may display activity against such infections. One such agent is fosfomycin, an oral drug with activity against a variety of Gram-positive and -negative bacteria, but only approved for use in the USA for urinary tract infection (UTI) due to Escherichia coli and Enterococcus faecalis. The purpose of this study was to assess the efficacy of fosfomycin treatment of MDR UTI and identify predictors of outcome. PATIENTS AND METHODS A retrospective review was performed of patients treated for MDR UTI at a large quaternary medical centre between 1 January 2010 and 30 September 2014. Sixty patients received 69 courses of fosfomycin in the inpatient or outpatient setting for UTIs due to Enterobacteriaceae, Pseudomonas aeruginosa or VRE. RESULTS In the 58 patients for whom follow-up data were available, the treatment success rate (no persistent or recurrent infection) was 55%. Chronic kidney disease was associated with persistent infection (OR = 3.56, 95% CI = 1.02-12.40, P = 0.04). No other factors, including comorbidities, infecting organism, fosfomycin MIC or number of doses of fosfomycin received, were associated with recurrent infection or treatment failure. CONCLUSIONS This study supports the use of fosfomycin as an oral option for treating MDR UTIs. Additional studies are required to assess the optimal dosing and utility of combination therapy to decrease the incidence of treatment failure.