Maddalena Peghin

Effects of Immunocompromise and Comorbidities on Pneumococcal Serotypes Causing Invasive Respiratory Infection in Adults: Implications for Vaccine Strategies

BACKGROUNDnThe 13-valent pneumococcal conjugate vaccine (PCV13) has recently been approved for use in immunocompromised adults. However, it is unclear whether there is an association between specific underlying conditions and infection by individual serotypes. The objective was to determine the prevalence of serotypes covered by PCV13 in a cohort of patients with invasive pneumococcal disease of respiratory origin and to determine whether there are specific risk factors for each serotype.nnnMETHODSnAn observational study of adults hospitalized with invasive pneumococcal disease in 2 Spanish hospitals was conducted during the period 1996-2011. A multinomial regression analysis was performed to identify conditions associated with infection by specific serotypes (grouped according their formulation in vaccines and individually).nnnRESULTSnA total of 1094 patients were enrolled; the infecting serotype was determined in 993. In immunocompromised patients, 64% of infecting serotypes were covered by PCV13. After adjusting for age, smoking, alcohol abuse, and nonimmunocompromising comorbidities, the group of serotypes not included in either PCV13 or PPV23 were more frequently isolated in patients with immunocompromising conditions and cardiopulmonary comorbidities. Regarding individual serotypes, 6A, 23F, 11A, and 33F were isolated more frequently in patients with immunocompromise and specifically in some of their subgroups. The subgroup analysis showed that serotype10A was also associated with HIV infection.nnnCONCLUSIONSnSpecific factors related to immunocompromise seem to determine the appearance of invasive infection by specific pneumococcal serotypes. Although the coverage of serotypes in the 13-valent conjugate pneumococcal vaccine (PCV13) was high, some non-PCV13-emergent serotypes are more prevalent in immunocompromised patients.

The management of multidrug-resistant Enterobacteriaceae.

Purpose of review Multidrug-resistant (MDR) Enterobacteriaceae are often related to the production of extended-spectrum b-lactamases (ESBLs) and carbapenemase-producing Enterobacteriaceae (CRE), and represent an increasing global threat. Recommendations for the therapeutic management of MDR-related infections, however, are mainly derived from retrospective and nonrandomized prospective studies. The aim of this review is to discuss the challenges in the treatment of patients with infections because of MDR Enterobacteriaceae and provide an expert opinion while awaiting for more definitive data. Recent findings To avoid the selection of carbapenemase-producing Enterobacteriaceae, carbapenem-sparing strategies should be considered. B-lactams/b-lactamase inhibitors, mainly piperacillin–tazobactam, minimum inhibitory concentration (MIC) 16/4mg/ml or less represents the best alternative to carbapenems for the treatment of ESBL-producing strains. Overall, combination therapy may be preferred over monotherapy for CRE. The combination of a carbapenem-containing regimen with colistin or high-dose tigecycline or aminoglycoside can be administered at high-dose prolonged infusion with therapeutic drug monitoring for the treatment of CRE with MIC for meropenem 8–16 mg/l or less. For MIC higher than 8–16 mg/l, the use of meropenem should be avoided and various combination therapies based on the in-vitro susceptibility of antimicrobials (e.g., colistin, high-dose tigecycline, fosfomycin, and aminoglycosides) should be selected. Summary Carbapenem-sparing strategies should be used, when feasible, for ESBL infections. The majority of available nonrandomized studies highlight that combination for CRE seem to offer some therapeutic advantage over monotherapy. Strict infection control measures toward MDR Gram-negative pathogens remain necessary while awaiting for new treatment options.

Environmental variables associated with an increased risk of invasive aspergillosis

Information on the environmental variables that may affect the incidence of invasive aspergillosis (IA) is scarce. We sought to determine the relationship between airborne spore counts, climatic conditions and IA. We also examined whether circulating respiratory viruses predispose patients to IA in a multicentre cohort study of hospitalized adults with IA. Data on environmental mould spores, climatic conditions and circulating respiratory viruses were obtained from the Environmental Department of the Autonomous University of Barcelona, the Meteorological Service of Catalonia and the Acute Respiratory Infection Surveillance Project in Catalonia, respectively. Between 2008 and 2011, 165 patients with IA were identified. Diagnosis was based on one or more of the following: culture (125 cases), galactomannan antigen (98) and histology (34). One hundred and twenty-seven cases (77%) had criteria for probable IA and the remainder for proven IA. Environmental mould spore counts from the period 28-42xa0days preceding infection presented significant associations with admissions due to IA. None of the climatic conditions were associated with an increased risk of IA, but the presence of circulating respiratory viruses was associated with a higher risk of infection: the most strongly associated viruses were respiratory syncytial virus, influenza A(H1N1)pdm09 and adenovirus. In conclusion, the presence of high numbers of spores in the air increases the risk of admission due to IA. Circulating respiratory viruses appear to be associated with a higher risk of developing IA. Physicians should be aware of this association in order to optimize prevention and diagnosis strategies for IA during viral epidemic periods.

Invasive Candida Infections in Liver Transplant Recipients: Clinical Features and Risk Factors for Mortality

Background Invasive fungal infections remain a leading cause of morbidity and mortality among liver transplant recipients (LTRs). In this patient population, invasive Candida infections (ICIs) account for the large majority of cases. To date, only small studies and case-series analysing clinical presentation and risk factors for mortality in LTRs with ICIs are available. Methods We performed a retrospective multicenter multinational study in 10 centers in Europe and Brazil. All consecutive LTRs developing ICIs during the period January 2011 to December 2013 were included in the study. Results A total of 42 LTRs were included. Median age was 52.5 years, and 78.6% of patients were men. Viral hepatitis was the most common cause for liver transplantation (42.9%). Candidemia represented the majority of cases (24, 57.1%), followed by intra-abdominal candidiasis (18, 42.9%). Overall 30-day mortality was 23.8%, with higher mortality in patients with candidemia compared with intra-abdominal candidiasis (37.5% vs 5.6%, P = 0.02). Multivariate analysis showed candidemia to be a risk factor associated with mortality among LTRs presenting ICIs (odds ratio, 11.86; 95% confidence interval, 1.5-280; P = 0.01). Candida albicans represented the most common isolate (59.5%). High rates of antifungal resistances were found, with 16.7% and 4.8% of isolates displaying resistance to azoles and caspofungin, respectively. Conclusions Our study confirms the occurrence of high mortality rates in LTRs developing ICIs. Mortality rates varied according to the type of infection, with candidemia representing a risk factor for mortality. The high rates of antifungal resistance should be considered in the choice of the empiric antifungal regimen.

Patient specific risk stratification for antimicrobial resistance and possible treatment strategies in gram-negative bacterial infections

ABSTRACT Introduction: The isolation of multi-drug-resistant gram-negative (MDRGN) pathogens has progressively increased worldwide and has been associated with important delays in the prescription of an adequate antibiotic treatment, resulting in increased mortality rates. Patient’s stratification for MDRGN infections to optimize the prescription of an adequate empiric antimicrobial regimen is crucial. Areas covered: This article covers MDRGN epidemiology, with a specific focus on risk factors for harbouring infections sustained by extended-spectrum-Beta-lactamase (ESBL), carbapenem resistant Enterobacteriacae (CRE), MDR Pseudomonas aeruginosa and MDR Acinetobacter baumanii. Moreover, we will propose an algorithm for the choice of empiric treatment when a MDRGN infection is suspected. Expert commentary: Although in clinical practice, a patient’s stratification represents a challenge, whenever a MDRGN pathogen is suspected broad-spectrum, combination empiric treatment should be promptly started, looking for a balance between the prescription of an adequate empiric treatment and the risk of resistance selection.

Efficacy of β-Lactam/β-Lactamase Inhibitor Combinations for the Treatment of Bloodstream Infection Due to Extended-Spectrum-β-Lactamase-Producing Enterobacteriaceae in Hematological Patients with Neutropenia

ABSTRACT β-Lactam/β-lactamase inhibitors (BLBLIs) were compared to carbapenems in two cohorts of hematological neutropenic patients with extended-spectrum-β-lactamase (ESBL) bloodstream infection (BSI): the empirical therapy cohort (174 patients) and the definitive therapy cohort (251 patients). The 30-day case fatality rates and other secondary outcomes were similar in the two therapy groups of the two cohorts and also in the propensity-matched cohorts. BLBLIs might be carbapenem-sparing alternatives for the treatment of BSI due to ESBLs in these patients.

Clinical characteristics and predictors of mortality in cirrhotic patients with candidemia and intra-abdominal candidiasis: a multicenter study

PurposeThe aim of the study was to describe the characteristics of cirrhotic patients with candidemia and intra-abdominal candidiasis (IAC) and to evaluate the risk factors associated with 30-day mortality.MethodsA multicenter multinational retrospective study including all consecutive episodes of candidemia and IAC in adult patients with liver cirrhosis in 14 European hospitals during the period 2011–2013 was performed.ResultsA total of 241 episodes (169 candidemia, 72 IAC) were included. Most Candida infections were acquired in hospital (208, 86.3%), mainly in the intensive care unit (ICU) (121, 50.2%). At clinical presentation, fever was seen in 60.6% of episodes (146/241) and septic shock in 34.9% (84/241). C.xa0albicans was the most common species (found in 131 episodes, 54.4%), followed by C.xa0glabrata (35, 14.5%) and C.xa0parapsilosis (34, 14.1%). Overall, the 30-day mortality was 35.3%. Multivariable analysis identified candidemia (OR 2.2, 95% CI 1.2–4.5) and septic shock (OR 3.2, 95% CI 1.7–6) as independent factors associated with 30-day mortality. Adequate antifungal treatment (OR 0.4, 95% CI 0.3–0.9) was associated with survival benefit.ConclusionsA shift towards increasing prevalence of C.xa0glabrata and C.xa0parapsilosis species in patients with liver disease was documented. Candidemia and IAC were associated with significant mortality in cirrhotic patients. Thirty-day mortality was associated with candidemia and severe clinical presentation, whereas adequate antifungal treatment improved the prognosis.

Causes of Death in a Contemporary Cohort of Patients with Invasive Aspergillosis

Information regarding the processes leading to death in patients with invasive aspergillosis (IA) is lacking. We sought to determine the causes of death in these patients, the role that IA played in the cause, and the timing of death. The factors associated with IA-related mortality are also analyzed. We conducted a multicenter study (2008-2011) of cases of proven and probable IA. The causes of death and whether mortality was judged to be IA-related or IA-unrelated were determined by consensus using a six-member review panel. A multivariate analysis was performed to determine risk factors for IA-related death. Of 152 patients with IA, 92 (60.5%) died. Mortality was judged to be IA-related in 62 cases and IA-unrelated in 30. The most common cause of IA-related death was respiratory failure (50/62 patients), caused primarily by Aspergillus infection, although also by concomitant infections or severe comorbidities. Progression of underlying disease and bacteremic shock were the most frequent causes of IA-unrelated death. IA-related mortality accounted for 98% and 87% of deaths within the first 14 and 21 days, respectively. Liver disease (HR 4.54; 95% CI, 1.69-12.23) was independently associated with IA-related mortality, whereas voriconazole treatment was associated with reduced risk of death (HR 0.43; 95% CI, 0.20-0.93). In conclusion, better management of lung injury after IA diagnosis is the main challenge for physicians to improve IA outcomes. There are significant differences in causes and timing between IA-related and IA–unrelated mortality and these should be considered in future research to assess the quality of IA care.

Multidrug-resistant Pseudomonas aeruginosa skin and soft-tissue infection successfully treated with ceftolozane/tazobactam

Ceftolozane/tazobactam (C/T) is a novel β-lactam/β-lactamase inhibitor combination antibiotic approved by the US Food and Drug Administration for the treatment of complicated intra-abdominal and urinary tract infections due to Gram-negative bacteria, particularly extended-spectrum β-lactamase-producing Enterobacteriaceae and multidrug-resistant (MDR) Pseudomonas aeruginosa strains. Here we report a case of MDR P. aeruginosa skin and soft-tissue infection successfully treated with C/T.

Ceftolozane/tazobactam for the treatment of MDR Pseudomonas aeruginosa left ventricular assist device infection as a bridge to heart transplant

BackgroundCeftolozane/tazobactam (C/T) is a novel antibiotic with enhanced microbiological activity against multidrug-resistant (MDR) gram-negative bacteria, including MDR Pseudomonas aeruginosa.Case reportFive months after left ventricular assist device (LVAD) implantation, a 49-year old man developed fever and blood culture was positive for MDR P. aeruginosa, susceptible only to aminoglycosides, ciprofloxacin and colistin. A diagnosis of LVAD-related infection was made based on persistent bacteremia associated with moderate 18 F-fluorodeoxyglucose positron emission tomography/CT uptake in the left ventricular apex. Disk diffusion testing for C/T was performed (MIC 2 μg/mL) and intravenous antibiotic therapy with C/T and amikacin was started, with clinical and microbiological response. Initial conservative management with 6 weeks of systemic antibiotic therapy was attempted, but the patient relapsed one month after antibiotic discontinuation. Priority for transplantation was given and after 4 weeks of antibiotic therapy (C/T + amikacin), LVAD removal and heart transplant were performed, with no infection relapse.ConclusionsWe reported the first off-label use of C/T in the management of MDR P. aeruginosa LVAD infection as a bridge to heart transplant. C/T has shown potent anti-pseudomonal activity and good safety profile making this drug as a good candidate for suppressive strategy in intravascular device-associated bloodstream infections caused by MDR P. aeruginosa.