Background.Risk factors for Nocardia infection in organ transplant recipients have not been formally assessed in the current era of transplantation. Methods.We performed a matched case-control study ...(1 : 2 ratio) between January 1995 and December 2005. Control subjects were matched for transplant type and timing. Univariate matched odds ratios were determined and conditional logistic regression was performed to identify independent risk factors. Clinical and microbiological characteristics of all case patients were reviewed. Results.Among 5126 organ transplant recipients, 35 (0.6%) were identified as having cases of Nocardia infection. The highest frequency was among recipients of lung transplants (18 3.5% of 521 patients), followed by recipients of heart (10 2.5% of 392), intestinal (2 1.3% of 155), kidney (3 0.2% of 1717), and liver (2 0.1% of 1840) transplants. In a comparison of case patients with 70 matched control subjects, receipt of high-dose steroids (odds ratio, 27; 95% confidence interval, 3.2–235; P = .003) and cytomegalovirus disease (odds ratio, 6.9; 95% confidence interval, 1.02–46; P = .047) in the preceding 6 months and a high median calcineurin inhibitor level in the preceding 30 days (odds ratio, 5.8; 95% confidence interval, 1.5–22; P = .012) were found to be independent risk factors for Nocardia infection. The majority of case patients (27 77% of 35) had pulmonary disease only. Seven transplant recipients (20%) had disseminated disease. Nocardia nova was the most common species (found in 17 49% of the patients), followed by Nocardia farcinica (9 28%), Nocardia asteroides (8 23%), and Nocardia brasiliensis (1 3%). Of the 35 case patients, 24 (69%) were receiving trimethoprim-sulfamethoxazole for Pneumocystis jirovecii pneumonia prophylaxis. Thirty-one case patients (89%) experienced cure of their Nocardia infection. Conclusions.Receipt of high-dose steroids, history of cytomegalovirus disease, and high levels of calcineurin inhibitors are independent risk factors for Nocardia infection in organ transplant recipients. Our study provides insights into the epidemiology of Nocardia infection in the current era, a period in which immunosuppressive and prophylactic regimens have greatly evolved.
Treatment of Acinetobacter Infections Fishbain, Joel; Peleg, Anton Y.
Clinical infectious diseases,
07/2010, Letnik:
51, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Acinetobacter baumannii remains an important and difficult-to-treat pathogen whose resistance patterns result in significant challenges for the clinician. Despite the prevalence and interest in A. ...baumannii infections, there is relatively limited wellcontrolled scientific data to help the clinician select optimal empirical and subsequent targeted therapy for a variety of infections. We will review the currently available antimicrobial agents and discuss the clinical data supporting the use of the various agents.
Long-term care facilities (LTCFs) are a potentially important reservoir of multidrug-resistant (MDR) organisms; however, limited data exist.
A point-prevalence study was conducted in four co-located ...LTCFs in Australia. Nasal and rectal swabs were cultured for methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE) and MDR Gram-negative bacilli (GNB). Molecular typing and resistance detection were performed. Risk factors for colonization with an MDR organism were determined using a nested case-control study.
Consent was obtained from 115 (85%) of 136 eligible participants. Forty-one (36%) residents carried at least one type of MDR organism. The prevalence was 16% MRSA (n = 18), 6% VRE (n = 7) and 21% MDR GNB n = 24; including extended-spectrum β-lactamase (ESBL)-producing Escherichia coli (n = 12) and Acinetobacter baumannii (n = 6). The majority of ESBL-producing E. coli and A. baumannii were clonal. Current wound management adjusted OR (AOR) 8.81 (95% CI 2.78-27.94), P < 0.001, medical device in situ AOR 5.58 (95% CI 1.34-23.32), P = 0.018 and pressure ulcer AOR 3.69 (95% CI 1.06-12.86), P = 0.04 were independent risk factors for MDR organism colonization. Advanced dementia AOR 3.54 (95% CI 1.23-10.23), P = 0.02 and prolonged antibiotic use AOR 2.95 (95% CI 1.01-8.60), P = 0.047 were independently associated with MRSA colonization, whilst current wound management AOR 15.59 (95% CI 4.85-50.10), P < 0.001 and fluoroquinolone use AOR 4.27 (95% CI 1.20-15.25), P = 0.025 were risk factors for MDR GNB colonization.
LTCFs are an important reservoir of MDR organisms, with person-to-person transmissions being a potential issue. We have identified several predictors of colonization with MDR organisms, allowing a more targeted management of high-risk residents.
Background. Alemtuzumab is being increasingly used for the prevention and/or treatment of acute allograft rejection in organ transplant recipients. We assessed the risks of infection in, to our ...knowledge, the largest cohort and broadest range of organ transplant recipients yet reported to have received alemtuzumab. Methods. All patients who received alemtuzumab from September 2002 through March 2004, either as induction therapy at the time of transplantation or for the treatment of rejection, were evaluated for the development of an opportunistic infection (OI) until death or for 12 months after receipt of the last dose of alemtuzumab. Results. A total of 547 recipients were included, 65% of whom received alemtuzumab for induction therapy only. Overall, 56 recipients (10%) developed 62 OIs, including cytomegalovirus disease (n = 16), BK virus infection (n = 12), posttransplantation lymphoproliferative disease (n = 5), human herpesvirus 6 infection (n = 1), parvovirus infection (n = 1), esophageal candidiasis (n = 12), cryptococcosis (n = 2), invasive mold infection (n = 4), Nocardia infection (n = 4), mycobacterial infection (n = 3), Balamuthia mandrillaris infection (n = 1), and toxoplasmosis (n = 1). Patients who received alemtuzumab for induction therapy were significantly less likely to develop an OI, compared with patients who received alemtuzumab for rejection therapy (4.5% vs. 21%; P < .001). Independent predictors of the development of an OI were administration of alemtuzumab for rejection therapy (odds ratio OR, 3.5; 95% confidence interval CI, 1.8–6.8; P < .001), allograft failure (OR, 2.1; 95% CI, 1.1–4.4; P = .04), and receipt of a lung transplant (OR, 3.7; 95% CI, 1.7–8.0; P = .001) or an intestinal transplant (OR, 8.3; 95% CI, 3.5–19.5; P < .001). Conclusions. Patients who received alemtuzumab for the treatment of allograft rejection were significantly more likely to develop an OI, compared with patients who received alemtuzumab for induction therapy only. Such data have implications for new antimicrobial prophylactic strategies.
The ability of Staphylococcus aureus to rapidly acquire antibiotic resistance in the face of antimicrobial challenge has enabled it to remain an ongoing, significant human pathogen. Mechanisms behind ...the evolution of resistance in S. aureus are well documented, but the effects of these phenotypes upon virulence are less clear. By exploring available clinical and experimental data, we have shown that a number of the major steps in the evolution of antibacterial resistance in S. aureus have been accompanied by alterations in virulence. This review also highlights that further experimentation is required to fully elucidate the mechanisms involved in the interface between virulence and antibiotic resistance, with the intention of identifying novel preventative or therapeutic strategies for this important human pathogen.
Abstract
Introduction
This study aims to assess the association of piperacillin/tazobactam and meropenem minimum inhibitory concentration (MIC) and beta-lactam resistance genes with mortality in the ...MERINO trial.
Methods
Blood culture isolates from enrolled patients were tested by broth microdilution and whole genome sequencing at a central laboratory. Multivariate logistic regression was performed to account for confounders. Absolute risk increase for 30-day mortality between treatment groups was calculated for the primary analysis (PA) and the microbiologic assessable (MA) populations.
Results
In total, 320 isolates from 379 enrolled patients were available with susceptibility to piperacillin/tazobactam 94% and meropenem 100%. The piperacillin/tazobactam nonsusceptible breakpoint (MIC >16 mg/L) best predicted 30-day mortality after accounting for confounders (odds ratio 14.9, 95% confidence interval CI 2.8–87.2). The absolute risk increase for 30-day mortality for patients treated with piperacillin/tazobactam compared with meropenem was 9% (95% CI 3%–15%) and 8% (95% CI 2%–15%) for the original PA population and the post hoc MA populations, which reduced to 5% (95% CI −1% to 10%) after excluding strains with piperacillin/tazobactam MIC values >16 mg/L. Isolates coharboring extended spectrum β-lactamase (ESBL) and OXA-1 genes were associated with elevated piperacillin/tazobactam MICs and the highest risk increase in 30-day mortality of 14% (95% CI 2%–28%).
Conclusions
After excluding nonsusceptible strains, the 30-day mortality difference from the MERINO trial was less pronounced for piperacillin/tazobactam. Poor reliability in susceptibility testing performance for piperacillin/tazobactam and the high prevalence of OXA coharboring ESBLs suggests that meropenem remains the preferred choice for definitive treatment of ceftriaxone nonsusceptible Escherichia coli and Klebsiella.
Piperacillin/tazobactam should be avoided for ceftriaxone nonsusceptible Escherichia coli and Klebsiella spp. bloodstream infections, especially when minimum inhibitory concentrations are > 16 mg/L. Further assessment of current testing is warranted given disparity between commonly used methods and broth microdilution.
Infections remain important contributors to mortality in hematopoietic stem cell transplantation (HSCT).
Method
We studied the evolving epidemiology and trends in susceptibility of bacterial and ...Candida isolates at an Australian HSCT center. A total of 528 HSCTs in 508 patients were performed from April 2001 to May 2010. A total of 605 isolates were eligible for study inclusion; 318 (53%) were gram‐positive, 268 (44%) were gram‐negative, and 19 (3%) were Candida species.
Results
The most common site for isolates was blood (380 isolates, 63%). Staphylococcus aureus was the most common gram‐positive organism (n = 107, 34%), but trends to increasing coagulase‐negative staphylococci (P = 0.002) and vancomycin‐resistant Enterococcus (P < 0.001) were observed. Escherichia coli was the most common gram‐negative isolate (n = 74, 28%). Fluoroquinolone resistance increased with widespread use of protocol fluoroquinolone prophylaxis (P = 0.001). Carbapenem resistance was found in 44% of Pseudomonas or Acinetobacter isolates. Bloodstream infection with a multidrug‐resistant organism (odds ratio 3.61, 95% confidence interval: 1.40–9.32, P = 0.008) was an independent predictor of mortality at 7 days after a positive blood culture.
Conclusions
Antimicrobial resistance is an increasing problem in this vulnerable patient population, and not only has an impact on choice of empiric therapy for febrile neutropenia but also on mortality.
We determined the antibiotic susceptibility and genetic mechanisms of resistance in clinical strains of Acinetobacter baumannii from Istanbul, Turkey. A total of 101 clinical strains were collected ...between November 2011 and July 2012. Antimicrobial susceptibility was performed using the Vitek 2 Compact system and E-test. Multiplex PCR was used for detecting blaOXA-51-like, blaOXA.-23-like, blaOXA-40-like and blaOXA-58-like genes. ISAba1, blaIMP-like, blaVIM-like, blaGES, blaVEB, blaPER-2, aac-3-Ia and aac-6'-Ib and NDM-1 genes were detected by PCR and sequencing. By multiplex PCR, all strains were positive for blaOXA-51, 79 strains carried blaOXA-23 and one strain carried blaOXA-40. blaOXA-51 and blaOXA-23 were found together in 79 strains. ISAba1 element was detected in 81 strains, and in all cases it was found upstream of blaOXA-51. GES-type carbapenemases were found in 24 strains (GES-11 in 16 strains and GES-22 in 8 strains) while blaPER-2, blaVEB-1, blaNDM-1, blaIMP- and blaVIM-type carbapenemases were not observed. Aminoglycoside modifying enzyme (aac-3-Ia and aac-6'Ib) genes were detected in 13 and 15 strains, respectively. Ninety-seven (96%) A. baumannii strains were defined as MDR and of these, 98% were extensively drug resistant (sensitive only to colistin). Colistin remains the only active compound against all clinical strains. As seen in other regions, OXA-type carbapenemases, with or without an upstream ISAba1, predominate but GES-type carbapenemases also appear to have a significant presence. REP-PCR analysis was performed for molecular typing and all strains were collected into 12 different groups. To our knowledge, this is the first report of GES-11 and OXA-40 in A. baumannii from Turkey.
Screening for latent tuberculosis infection (LTBI) is recommended prior to organ transplantation. The Quantiferon‐TB Gold assay (QFT‐G) may be more accurate than the tuberculin skin test (TST) in the ...detection of LTBI. We prospectively compared the results of QFT‐G to TST in patients with chronic liver disease awaiting transplantation. Patients were screened for LTBI with both the QFT‐G test and a TST. Concordance between test results and predictors of a discordant result were determined. Of the 153 evaluable patients, 37 (24.2%) had a positive TST and 34 (22.2%) had a positive QFT‐G. Overall agreement between tests was 85.1% (κ= 0.60, p < 0.0001). Discordant test results were seen in 12 TST positive/QFT‐G negative patients and in 9 TST negative/QFT‐G positive patients. Prior BCG vaccination was not associated with discordant test results. Twelve patients (7.8%), all with a negative TST, had an indeterminate result of the QFT‐G and this was more likely in patients with a low lymphocyte count (p = 0.01) and a high MELD score (p = 0.001). In patients awaiting liver transplantation, both the TST and QFT‐G were comparable for the diagnosis of LTBI with reasonable concordance between tests. Indeterminate QFT‐G result was more likely in those with more advanced liver disease.
The Quantiferon‐Gold In‐Tube assay was comparable to the tuberculin skin test for the diagnosis of latent tuberculosis infection in liver transplant candidates.
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