V. Del Bono

Piperacillin/tazobactam (Tazocin™) seems to be no longer responsible for false-positive results of the galactomannan assay.

OBJECTIVES Galactomannan (GM) testing is extremely useful for diagnosing invasive aspergillosis in high-risk patients, but false-positive results have been reported in patients treated with piperacillin/tazobactam. The aims of this study are to test if the recent piperacillin/tazobactam (Tazocin™; Pfizer) preparation still contains GM, and if serum GM positivity in haematopoietic stem cell transplant (HSCT) recipients receiving piperacillin/tazobactam can be attributed to this treatment. PATIENTS AND METHODS Serum samples obtained from 1 October 2009 to 31 October 2010 from HSCT recipients for GM testing were analysed. The difference in the rate of positive results (defined as GM ≥ 0.5) in patients receiving and not receiving piperacillin/tazobactam was evaluated. Piperacillin/tazobactam vials from randomly selected batches were tested. RESULTS Of 1606 samples drawn in the absence of piperacillin/tazobactam therapy, 25 (1.6%) tested positive for GM versus 10 of 394 samples (2.5%) drawn while on piperacillin/tazobactam (P = 0.18). The median GM result of samples drawn on piperacillin/tazobactam was slightly higher than that of samples drawn in the absence of piperacillin/tazobactam (0.141 versus 0.122; P < 0.001). All 90 piperacillin/tazobactam vials from 30 randomly selected batches tested negative for GM, with a median GM value of 0.057 (range: 0.011-0.320). CONCLUSIONS Although some residual GM might still be present in piperacillin/tazobactam, currently available brand piperacillin/tazobactam preparations seem no longer responsible for false-positive GM results.

Cotrimoxazole therapy ofToxoplasma gondii encephalitis in AIDS patients

Twenty-four consecutive HIV-positive patients affected byToxoplasma gondii encephalitis received trimethoprim-sulfamethoxazole (cotrimoxazole) as acute-phase treatment. Two dosage regimens of cotrimoxazole were used: 40 mg/kg/day (12 patients) or 120 mg/kg/day (12 patients) of total compound (trimethoprim plus sulfamethoxazole). Clinical and radiological responses to treatment were evaluated, and the product-limit method for survival data analysis was used. Eighteen of 24 patients showed both a clinical and radiological response (75 % response rate). There were no differences in response rates between patients receiving the two dosage regimens of cotrimoxazole. Adverse reaction consisted of leukopenia (two cases) and skin rash (three cases) which led to the discontinuation of the drug in one case. These results suggest that a randomized, controlled clinical trial should be carried out comparing cotrimoxazole versus sulfadiazine-pyrimethamine in AIDS patients withToxoplasma gondii encephalitis.

Hepatitis B reactivation in HBsAg-negative/HBcAb-positive allogeneic haematopoietic stem cell transplant recipients: risk factors and outcome

HBsAg-negative/HBcAb-positive haematopoietic stem cell transplant (HSCT) recipients are at high risk of hepatitis B virus (HBV) reactivation. Allogeneic HSCT recipients from years 2000 to 2010 were evaluated in order to study the impact of being HBsAg-negative/HBcAb-positive in this population. Overall, 137 of 764 patients (18%) were HBsAg-negative/HBcAb-positive before HSCT. Overall survival, non-relapse mortality (NRM), acute and chronic graft-vs.-host disease were similar in HBcAb-positive and HBcAb-negative patients. Reactivation occurred in 14 patients (10%) within a median of 19 months after HSCT (range 9-77). Cause-specific hazard for reactivation was decreased in the case of an HBV-immune/exposed donor (HRadjusted = 0.12; 95% CI, 0.02-0.96; p 0.045) and increased in patients who received rituximab treatment (HRadjusted = 2.91; 95%CI, 0.77-10.97; p 0.11). Competing risk analyses documented a protective role of an HBV-immune/exposed donor (p 0.041) and an increased probability associated with the length of treatment with cyclosporine (p <0.001) and treatment with rituximab (but not with low-dose rituximab prophylaxis, p <0.001 at each landmark point). No differences in overall survival and NRM were found between patients with and without HBV reactivation. The donors immunity was independently and consistently associated with a decreased risk of HBV reactivation, while rituximab and cyclosporine treatments increased the probability.

An Italian consensus for invasive candidiasis management (ITALIC).

Invasive candidiasis (IC) has primarily been studied in intensive care unit (ICU) patients, although, in reality, a vast majority of these infections occur outside of the ICU. The recent publication of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guidelines also deal with the non-ICU population, but many uncertainties remain on the management of IC, particularly in non-critically ill patients. The Italian Society of Antimicrobial Therapy, Società Italiana di Terapia Antimicrobica (SITA), produced practical, hospital-wide recommendations on the management of Candida infection in non-immunocompromised patients in the hospital ward. Our focus is on patient stratification in terms of risk factors for IC and of clinical severity, emphasising a high index of suspicion to ensure early diagnosis, early treatment and de-escalation when a patient is clinically stable, in order to optimise resource allocation.

Initial serum (1,3)-β-d-glucan as a predictor of mortality in proven candidaemia: findings from a retrospective study in two teaching hospitals in Italy and Brazil

A retrospective study was conducted to assess the role of initial serum (1,3)-β-d-glucan (BDG) values in predicting mortality in proven candidaemia. The study was conducted in two large teaching hospitals in Italy and Brazil. From January 2009 to June 2014, all patients with proven candidaemia who underwent a BDG test within 96 hours before or after the first positive blood culture were included in the study. The primary end point was 28-day mortality, with the role of initial BDG being assessed by univariate and multivariate analyses. A total of 104 patients met the inclusion criteria. Overall, the crude 28-day mortality was 30% (31/104). In the final multivariate model, an initial BDG of >287 pg/mL (odds ratio (OR) 4.40, 95% confidence interval (CI) 1.56-12.39, p 0.005), haemodialysis (OR 4.33, 95% CI 1.24-15.17, p 0.022) and a Pitt score of ≥ 2 (OR 4.10, 95% CI 1.24-13.54, p 0.021) were significant predictors of 28-day mortality. The >287 pg/mL cutoff predicted 28-day mortality with 65% sensitivity and 70% specificity. Centre of enrolment (p for interaction 0.012), haemodialysis (p for interaction 0.062) and timing of BDG test of more than 24 hours before or after the positive culture (p for interaction 0.143) appeared to interact with BDGs ability to predict mortality. Although not statistically significant, the last two of these interactions might partially explain why BDGs ability to predict mortality was present only in the Italian cohort.

Early carbapenem-resistant Klebsiella pneumoniae bacteraemia: should we expand the screening?

Keywords: acrive screening; carbapenem resistance; carbapenemases; carbapenemase-producing Enterobacteriaceae; infection control; Klebsiella pneumoniae; KPC

Increasing incidence of Clostridium difficile infections: results from a 5-year retrospective study in a large teaching hospital in the Italian region with the oldest population.

Limited information is available on the incidence of Clostridium difficile infections (CDIs) in Italian hospitals. In this study, we assessed the changes in the incidence of CDI over a 5-year period in a teaching hospital in Liguria, the Italian region with the oldest population. Secondary endpoints were the development of severe CDI and 30-day mortality. The annual incidence of CDI/10000 patient-days significantly increased from 0·54 in 2010 to 3·04 in 2014 (χ 2 for trend, P < 0·001). The median age of patients with CDI was 81 years. As many as 81% and 89% of these patients had comorbid conditions and previous exposure to antibiotics, respectively. In the multivariate analysis of risk factors for severe CDI, previous therapy with histamine 2 blockers and low serum albumin were associated with severe CDI, while diabetes appeared to be protective. In the multivariate model of risk factors for 30-day mortality, high leukocyte count, low serum albumin, and increased serum creatinine were unfavourably associated with outcome. Strict adherence to infection control measures was of utmost importance to counteract the increasing incidence of CDI in our hospital, particularly because of the advanced age of the patients and their very high frequency of chronic conditions and use of antibiotics, which readily predispose them to the development of CDI.

Guillain-Barré syndrome following chickenpox: a case series.

Guillain–Barré syndrome (GBS) is an acute, immune-mediated polyradiculoneuropathy, usually triggered by an infectious episode, mostly of viral origin. Varicella zoster virus (VZV) is a rare cause of GBS, mainly in the case of latent infection reactivation. We report on three adult patients who developed GBS following chickenpox, after a short period of latency. They were promptly treated with intravenous immunoglobulin, and the first one with plasma exchange additionally. All the patients experienced almost complete clinical recovery. Our experience suggests that primary VZV infection constitutes a GBS triggering event.

Anti-V3 loop spectrotype in HIV-infected individuals during zidovudine therapy.

SummaryIn order to investigate the role played by zidovudine (ZDV) as immune modulator, particularly on B-cell response, the anti-V3 loop spectrotype in 115 sera from 26 HIV-infected individuals was evaluated, prior to and during treatment with ZDV, by isoelectric focusing and reverse blotting (IEF-RB), a technique useful for indirectly measuring the activity and the number of B-cell clones. All 18 patients showing seroreactivity by IEFRB displayed a clear oligoclonal banding pattern, with no change in the spectrotype (i.e. new bands), in sequential analysis over the course of therapy. Only minor changes in band intensity were found, without any correlation with ZDV treatment or CD4+ cell count. In addition, among the sera reactive in spectrotypic analysis, the percentage of those with p24 antigen positivity was significantly lower than those with no detectable p24 antigen (19.8% vs 80.2%, respectively, p=<0.0001, Fishers exact test). In conclusion, it could not be demonstrated by IEFRB that there was any effect of ZDV on the activity and the number of anti-V3 specific B-cell clones. This data is in line with previous studies showing the constancy of anti-gp120 antibody spectrotype over the long course of the disease.ZusammenfassungDer Anti-V3-Loop-Spektrotyp wurden in 115 Seren von 26 HIV-Infizierten vor und nach Zidovudin-Therapie bestimmt, um die Rolle von Zidovudin als Immunmodulator, vor allem der B-Zell-Antwort, zu prüfen. Als Methoden wurden isoelektrische Fokussierung und reverses Blotting (IEFRB) eingesetzt, die sich für die indirekte Bestimmung der Aktivität und der Zahl der B-Zell-Klone als brauchbar erwiesen haben. Bei allen 18 seroreaktiven Patienten stellten sich eindeutige oligoklonale Bandenmuster dar. In Verlaufsanalysen während der Therapie war keine Änderung im Spektrotyp, d. h. keine neuen Banden, zu erkennen. Die Bandenintensität änderte sich nur wenig, wobei keine Beziehung zur Zidovudin-Therapie oder den CD4+ Zellzahlen bestand. In den Spektrotyp-positiven Seren war nur bei einem kleinen Anteil auch p24-Antigen nachzuweisen (19,8% positive gegen 80,2% p-24-Antigen negative Seren; p≤0,0001, Fishers exakter Test). Zusammenfassend fand sich mit IEFRB kein Einfluß von Zidovudin auf die Aktivität und die Zahl anti-V3-spezifischer B-Zell-Klone. Dies stimmt mit den Ergebnissen früherer Studien überein, in denen Konstanz des anti-gp120-Antikörper-Spektrotyps im Langzeitverlauf der Erkrankung festgestellt wurde.In order to investigate the role played by zidovudine (ZDV) as immune modulator, particularly on B-cell response, the anti-V3 loop spectrotype in 115 sera from 26 HIV-infected individuals was evaluated, prior to and during treatment with ZDV, by isoelectric focusing and reverse blotting (IEF-RB), a technique useful for indirectly measuring the activity and the number of B-cell clones. All 18 patients showing seroreactivity by IEFRB displayed a clear oligoclonal banding pattern, with no change in the spectrotype (i.e. new bands), in sequential analysis over the course of therapy. Only minor changes in band intensity were found, without any correlation with ZDV treatment or CD4+ cell count. In addition, among the sera reactive in spectrotypic analysis, the percentage of those with p24 antigen positivity was significantly lower than those with no detectable p24 antigen (19.8% vs 80.2%, respectively, p=<0.0001, Fishers exact test). In conclusion, it could not be demonstrated by IEFRB that there was any effect of ZDV on the activity and the number of anti-V3 specific B-cell clones. This data is in line with previous studies showing the constancy of anti-gp120 antibody spectrotype over the long course of the disease. Der Anti-V3-Loop-Spektrotyp wurden in 115 Seren von 26 HIV-Infizierten vor und nach Zidovudin-Therapie bestimmt, um die Rolle von Zidovudin als Immunmodulator, vor allem der B-Zell-Antwort, zu prüfen. Als Methoden wurden isoelektrische Fokussierung und reverses Blotting (IEFRB) eingesetzt, die sich für die indirekte Bestimmung der Aktivität und der Zahl der B-Zell-Klone als brauchbar erwiesen haben. Bei allen 18 seroreaktiven Patienten stellten sich eindeutige oligoklonale Bandenmuster dar. In Verlaufsanalysen während der Therapie war keine Änderung im Spektrotyp, d. h. keine neuen Banden, zu erkennen. Die Bandenintensität änderte sich nur wenig, wobei keine Beziehung zur Zidovudin-Therapie oder den CD4+ Zellzahlen bestand. In den Spektrotyp-positiven Seren war nur bei einem kleinen Anteil auch p24-Antigen nachzuweisen (19,8% positive gegen 80,2% p-24-Antigen negative Seren; p≤0,0001, Fishers exakter Test). Zusammenfassend fand sich mit IEFRB kein Einfluß von Zidovudin auf die Aktivität und die Zahl anti-V3-spezifischer B-Zell-Klone. Dies stimmt mit den Ergebnissen früherer Studien überein, in denen Konstanz des anti-gp120-Antikörper-Spektrotyps im Langzeitverlauf der Erkrankung festgestellt wurde.

Predictors of choice of initial antifungal treatment in intraabdominal candidiasis

Intraabdominal candidiasis (IAC) is the second most frequent form of invasive candidiasis, and is associated with high mortality rates. This study aims to identify current practices in initial antifungal treatment (IAT) in a real-world scenario and to define the predictors of the choice of echinocandins or azoles in IAC episodes. Secondary analysis was performed of a multinational retrospective cohort at 13 teaching hospitals in four countries (Italy, Greece, Spain and Brazil), over a 3-year period (2011-2013). IAC was identified in 481 patients, 323 of whom received antifungal therapy (classified as the treatment group). After excluding 13 patients given amphotericin B, the treatment group was further divided into the echinocandin group (209 patients; 64.7%) and the azole group (101 patients; 32.3%). Median APACHE II scores were significantly higher in the echinocandin group (p 0.013), but IAT did not differ significantly with regard to the Candida species involved. Logistic multivariate stepwise regression analysis, adjusted for centre effect, identified septic shock (adjusted OR (aOR) 1.54), APACHE II >15 (aOR 1.16) and presence in surgical ward at diagnosis (aOR 1.16) as the top three independent variables associated with an empirical echinocandin regimen. No differences in 30-day mortality were observed between groups. Echinocandin regimen was the first choice for IAT in patients with IAC. No statistical differences in mortality were observed between regimens, but echinocandins were administered to patients with more severe disease. Some disagreements were identified between current clinical guidelines and prescription of antifungals for IAC at the bedside, so further educational measures are required to optimize therapies.