Rossana Rosa

Surveillance Cultures Growing Carbapenem-Resistant Acinetobacter baumannii Predict the Development of Clinical Infections: A Retrospective Cohort Study

BACKGROUND We aimed to determine the effect of the presence of carbapenem-resistant Acinetobacter baumannii in accordance with surveillance cultures on the subsequent development of clinical infections by this organism. METHODS This retrospective cohort study was conducted at a tertiary hospital from January 2010 to November 2011. We included all consecutive patients admitted to the trauma intensive care unit, who had weekly surveillance cultures performed (from rectum, and if intubated, respiratory secretions), and without evidence of A. baumannii infections prior to the collection of the first surveillance culture. Univariable and multivariable analyses were performed using log-binomial regression. Survival analyses were performed using Cox proportional hazards. RESULTS Three hundred sixty-four patients were included, of whom 49 (13.5%) had carbapenem-resistant A. baumannii on surveillance cultures. Patients with positive surveillance cultures had 8.4 (95% confidence interval [CI], 5.6-12.7; P < .0001) times the risk of developing a subsequent A. baumannii infection compared with patients who remained negative on surveillance cultures. Multivariable analysis showed significant associations between clinical infection and both positive surveillance cultures (relative risk [RR], 5.9 [95% CI, 3.8-9.3]; P < .0001) and mechanical ventilation (RR, 4.3 [95% CI, 1.03-18.2]; P = .05). On survival analyses, the only variable associated with the development of clinical infections was the presence of positive surveillance cultures (hazard ratio, 16.3 [95% CI, 9.1-29.1]; P < .001). CONCLUSIONS Presence of carbapenem-resistant A. baumannii on surveillance cultures is strongly associated with subsequent development of carbapenem-resistant A. baumannii infections. Prevention efforts should be focused at limiting the acquisition of this organism during hospitalization.

Multicenter Evaluation of Ceftolozane/Tazobactam for Serious Infections Caused by Carbapenem-Resistant Pseudomonas aeruginosa

A multicenter, retrospective study of patients infected with carbapenem-resistant Pseudomonas aeruginosa who were treated with ceftolozane/tazobactam was performed. Among 35 patients, pneumonia was the most common indication and treatment was successful in 26 (74%). Treatment failure was observed in all cases where isolates demonstrated ceftolozane-tazobactam minimum inhibitory concentrations ≥8 μg/mL.

Environmental exposure to carbapenem-resistant Acinetobacter baumannii as a risk factor for patient acquisition of A. baumannii.

We aimed to determine the association between environmental exposure to carbapenem-resistant Acinetobacter baumannii and the subsequent risk of acquiring this organism. Patients exposed to a contaminated hospital environment had 2.77 times the risk of acquiring carbapenem-resistant A. baumannii than did unexposed patients (relative risk, 2.77 [95% confidence interval, 1.50-5.13]; P = .002).

In vitro discordance with in vivo activity: Humanized exposures of ceftazidime-avibactam, aztreonam, and tigecycline alone and in combination against New Delhi metallo-β-lactamase-producing Klebsiella pneumoniae in a murine lung infection model

ABSTRACT The management of infections with New Delhi metallo-beta-lactamase-1 (NDM)-producing bacteria remains clinically challenging given the multidrug resistant (MDR) phenotype associated with these bacteria. Despite resistance in vitro, ceftazidime-avibactam previously demonstrated in vivo activity against NDM-positive Enterobacteriaceae. Herein, we observed in vitro synergy with ceftazidime-avibactam and aztreonam against an MDR Klebsiella pneumoniae harboring NDM. In vivo, humanized doses of ceftazidime-avibactam monotherapy resulted in >2 log10 CFU bacterial reduction; therefore, no in vivo synergy was observed.

Twelve-week rifapentine plus isoniazid versus 9-month isoniazid for the treatment of latent tuberculosis in renal transplant candidates

Background Renal transplant candidates (RTC) with latent tuberculosis infection (LTBI) are at significant risk for tuberculosis reactivation. Twelve-week rifapentine (RPT)/isoniazid (INH) is effective for LTBI but clinical experience in RTC is scarce. Methods We conducted a retrospective study of RTC with LTBI treated with either 12-week RPT/INH or 9-month INH from March 1, 2012, through February 28, 2014. We evaluated both groups for differences in rates of treatment completion, monthly follow-up visit compliance, transaminase elevations, and adverse reactions leading to discontinuation of LTBI treatment. The utility of weekly reminders was also evaluated in the 12-week regimen. Direct observed therapy was not performed in our study. Results Of 153 patients, 43 (28%) and 110 (72%) were started on 12-week RPT/INH and 9-month INH, respectively. The treatment completion and monthly follow-up visit compliance rates were higher in the 12-week RPT/INH group (40 [93%] vs 52 [47%], P < 0.001) and (11/40 [28%] vs 13/104 [13%], P = 0.03), respectively. Transaminase elevations were not observed in the RPT/INH group, but occurred in 6 (5%) of the INH group. There were no differences in adverse reactions leading to discontinuation of LTBI treatment. Conclusions Twelve-week RPT/INH appears to be an excellent choice for LTBI in RTC. It has a higher treatment completion rate and causes less transaminase elevations, and weekly reminders may be an alternative when direct observed therapy is not feasible.

Solid organ transplant antibiograms: an opportunity for antimicrobial stewardship

OBJECTIVES We aimed to compare the antimicrobial susceptibility percentages in blood and urine bacterial isolates recovered from solid organ transplant (SOT) recipients with those reported in the hospital-wide antibiogram. METHODS Retrospective review of the antimicrobial susceptibilities of bacterial isolates recovered from SOT recipients at a 1550-bed hospital over a 2-year period. Antibiograms were categorized by anatomic site (blood and urine). Percentage of bacterial susceptibilities to specific antibiotics were compared with the hospital-wide antibiogram. RESULTS A total of 1889 unique cultures were identified. Blood and urine isolates of Escherichia coli, Klebsiella pneumonia and Pseudomonas aeruginosa had significantly lower susceptibility to first and second line antibiotics compared to the hospital-wide antibiogram. CONCLUSION Significant differences in susceptibilities between isolates from blood and urine cultures from SOT recipients and the hospital-wide antibiogram were found. A population-based strategy for the development of antibiograms specific for this group of high-risk patients could better guide appropriate empiric antimicrobial selection.

Pretransplant CD4 Count Influences Immune Reconstitution and Risk of Infectious Complications in Human Immunodeficiency Virus-Infected Kidney Allograft Recipients.

In current practice, human immunodeficiency virus–infected (HIV+) candidates with CD4 >200 cells/mm3 are eligible for kidney transplantation; however, the optimal pretransplant CD4 count above this threshold remains to be defined. We evaluated clinical outcomes in patients with baseline CD4 >350 and <350 cells/mm3 among 38 anti–thymocyte globulin (ATG)–treated HIV‐negative to HIV+ kidney transplants performed at our center between 2006 and 2013. Median follow‐up was 2.6 years. Rates of acute rejection and patient and graft survival were not different between groups. Occurrence of severe CD4 lymphopenia (<200 cells/mm3), however, was more common among patients with a baseline CD4 count 200–349 cells/mm3 compared with those transplanted at higher counts (75% vs. 30% at 4 weeks [p = 0.04] and 71% vs. 5% at 52 weeks [p = 0.001], respectively, after transplant). After adjusting for age, baseline CD4 count of 200–349 cells/mm3 was an independent predictor of severe CD4 lymphopenia at 4 weeks (relative risk [RR] 2.6; 95% confidence interval [CI] 1.3–5.1) and 52 weeks (RR 14.3; 95% CI 2–100.4) after transplant. Patients with CD4 <200 cells/mm3 at 4 weeks had higher probability of serious infections during first 6 months after transplant (19% vs. 50%; log‐rank p = 0.05). These findings suggest that ATG must be used with caution in HIV+ kidney allograft recipients with a pretransplant CD4 count <350 cells/mm3.

Phaeohyphomycosis due to Exophiala infections in solid organ transplant recipients: Case report and literature review

This case report and literature review underscores the cutaneous presentations of phaeohyphomycosis in the solid organ transplant population. Increased cognizance with prompt identification is critical. The therapy and clinical outcomes of phaeohyphomycosis, caused by the Exophiala genus, in the solid organ transplant population, is analyzed to examine optimal care. This review highlights the inherent difficulties in providing the appropriate duration of antifungal therapy to avoid relapsing infections in immunosuppressed patients.

Influence of immune activation on the risk of allograft rejection in human immunodeficiency virus-infected kidney transplant recipients

BACKGROUND HIV infection is associated with high rates of acute rejection following kidney transplantation. The underlying mechanisms for such predisposition are incompletely understood. Pathological immune activation is a hallmark of chronic HIV infection that persists despite effective antiretroviral therapy. We hypothesized that the baseline levels of T cell activation in HIV(+) candidates would correlate with their risk of acute rejection following kidney transplantation. METHODS Single-center retrospective cohort analysis of HIV(+) adult kidney transplants performed between October 2006 and September 2013. The frequency of CD3(+)HLA-DR(+) cells measured by flow cytometry served as a surrogate marker of immune activation. Patients were categorized into tertiles of activation, and the rates of biopsy-proven acute rejection were compared across groups. RESULTS (1) Compared to matched HIV(-) controls, the baseline number of CD3(+)HLA-DR(+) cells was higher in HIV(+) kidney transplant candidates. (2) Abnormally high levels of activation did not decrease with transplant-associated immunosuppression. (3) Patients categorized within the lower and middle CD3(+)HLA-DR(+) tertiles had higher probability of rejection during the first 3years post-transplant compared to those in the higher activation tertile (36.9% vs. 0%; log-rank P=0.04). CONCLUSIONS Pathological immune activation in HIV(+) transplant candidates does not explain their increased susceptibility to allograft rejection. Paradoxically, those with the highest levels of immune activation seem to be less prone to rejection.

Impact of antiretroviral therapy on clinical outcomes in HIV+ kidney transplant recipients: Review of 58 cases

Background: Antiretroviral therapy (ART) poses challenging drug-drug interactions with immunosuppressant agents in transplant recipients. We aimed to determine the impact of specific antiretroviral regimens in clinical outcomes of HIV + kidney transplant recipients. Methods: A single-center, retrospective cohort study was conducted at a large academic center. Subjects included 58 HIV - to HIV + adult, first-time kidney transplant patients. The main intervention was ART regimen used after transplantation. The main outcomes assessed at one- and three-years were: patient survival, death-censored graft survival, and biopsy-proven acute rejection; we also assessed serious infections within the first six months post-transplant. Results: Patient and graft survival at three years were both 90% for the entire cohort. Patients receiving protease inhibitor (PI)-containing regimens had lower patient survival at one and three years than patients receiving PI-sparing regimens: 85% vs. 100% ( p=0.06) and 82% vs. 100% ( p=0.03), respectively. Patients who received PI-containing regimens had twelve times higher odds of death at 3 years compared to patients who were not exposed to PIs (odds ratio, 12.05; 95% confidence interval, 1.31-1602; p=0.02). Three-year death-censored graft survival was lower in patients receiving PI vs. patients on PI-sparing regimens (82 vs 100%, p=0.03). Patients receiving integrase strand transfer inhibitors-containing regimens had higher 3-year graft survival. There were no differences in the incidence of acute rejection by ART regimen. Individuals receiving PIs had a higher incidence of serious infections compared to those on PI-sparing regimens (39 vs. 8%, p=0.01). Conclusions: PI-containing ART regimens are associated with adverse outcomes in HIV + kidney transplant recipients.