Elda Righi

Epidemiological trends in nosocomial candidemia in intensive care

BackgroundInfection represents a frequent complication among patients in Intensive Care Units (ICUs) and mortality is high. In particular, the incidence of fungal infections, especially due to Candida spp., has been increasing during the last years.MethodsIn a retrospective study we studied the etiology of candidemia in critically ill patients over a five-year period (1999–2003) in the ICU of the San Martino University Hospital in Genoa, Italy.ResultsIn total, 182 episodes of candidaemia were identified, with an average incidence of 2.22 episodes/10 000 patient-days/year (range 1.25–3.06 episodes). Incidence of candidemia increased during the study period from 1.25 in 1999 to 3.06/10 000 patient-days/year in 2003. Overall, 40% of the fungemia episodes (74/182) were due to C.albicans, followed by C. parapsilosis(23%), C.glabrata (15%), C.tropicalis (9%) and other species (13%). Candidemia due to non-albicans species increased and this was apparently correlated with an increasing use of azoles for prophylaxis or empirical treatment.ConclusionThe study demonstrates a shift in the species of Candida causing fungemia in a medical and surgical ICU population during a 5 year period. The knowledge of the local epidemiological trends in Candida species isolated in blood cultures is important to guide therapeutic choices.

Colistin and rifampicin in the treatment of multidrug-resistant Acinetobacter baumannii infections

OBJECTIVES The increased incidence of nosocomial infections by multidrug-resistant organisms has motivated the re-introduction of colistin in combination with other antimicrobials in the treatment of infections. We describe the clinical and microbiological outcomes of patients infected with multidrug-resistant Acinetobacter baumannii who were treated with a combination of colistin and rifampicin. PATIENTS AND METHODS Critically ill patients with pneumonia and bacteraemia caused by A. baumannii resistant to all antibiotics except colistin in medical and surgical intensive care units were enrolled. Clinical and microbiological responses and safety were evaluated. RESULTS Twenty-nine patients (47 +/- 14 years and APACHE II score 17.03 +/- 3.68), of whom 19 were cases of nosocomial pneumonia and 10 were cases of bacteraemia, were treated with intravenous colistin sulphomethate sodium (2 million IU three times a day) in addition to intravenous rifampicin (10 mg/kg every 12 h). All A. baumannii isolates were susceptible to colistin. The mean duration of treatment with intravenous colistin and rifampicin was 17.7 (+/-10.4) days (range 7-36). Clinical and microbiological responses were observed in 22 of 29 cases (76%) and the overall infection-related mortality was 21% (6/29). Three of the 29 evaluated patients (10%) developed nephrotoxicity when treated with colistin, all of whom had previous renal failure. No cases of renal failure were observed among patients with normal baseline renal function. No neurotoxicity was noted. CONCLUSIONS Colistin and rifampicin appears to be an effective and safe combination therapy for severe infections due to multidrug-resistant A. baumannii.

Epidemiology, Species Distribution, Antifungal Susceptibility, and Outcome of Candidemia across Five Sites in Italy and Spain

ABSTRACT Candidemia has become an important bloodstream infection that is frequently associated with high rates of mortality and morbidity, and its growing incidence is related to complex medical and surgical procedures. We conducted a multicenter study in five tertiary care teaching hospitals in Italy and Spain and evaluated the epidemiology, species distribution, antifungal susceptibilities, and outcomes of candidemia episodes. In the period of 2008 to 2010, 995 episodes of candidemia were identified in these hospitals. The overall incidence of candidemia was 1.55 cases per 1,000 admissions and remained stable during the 3-year analysis. Candida albicans was the leading agent of infection (58.4%), followed by Candida parapsilosis complex (19.5%), Candida tropicalis (9.3%), and Candida glabrata (8.3%). The majority of the candidemia episodes were found in the internal medicine department (49.6%), followed by the surgical ward, the intensive care unit (ICU), and the hemato-oncology ward. Out of 955 patients who were eligible for evaluation, 381 (39.9%) died within 30 days from the onset of candidemia. Important differences in the 30-day mortality rates were noted between institutions: the lowest mortality rate was in the Barcelona hospital, and the highest rate was in the Udine hospital (33.6% versus 51%, respectively; P = 0.0005). Overall, 5.1% of the 955 isolates tested were resistant or susceptible dose dependent (SDD) to fluconazole, with minor differences between the hospitals in Italy and Spain (5.7% versus 3.5%, respectively; P = 0.2). Higher MICs for caspofungin were found, especially with C. parapsilosis complex (MIC90, 1 μg/ml). Amphotericin B had the lowest MICs. This report shows that candidemia is a significant source of morbidity in Europe, causing a substantial burden of disease and mortality.

Drug treatment for multidrug-resistant Acinetobacter baumannii infections

Acinetobacter baumannii has emerged in the last decades as a major cause of healthcare-associated infections and nosocomial outbreaks. Multidrug-resistant (MDR) A. baumannii is a rapidly emerging pathogen in healthcare settings, where it causes infections that include bacteremia, pneumonia, meningitis, and urinary tract and wound infections. Antimicrobial resistance poses great limits for therapeutic options in infected patients, especially if the isolates are resistant to the carbapenems. Other therapeutic options include sulbactam, aminoglycosides, polymixyns and tigecycline. The discovery of new therapies coupled with the development of controlled clinical trial antibiotic testing combinations and the prevention of transmission of MDR Acinetobacter infection are essential to face this important hospital problem.

Candidaemia in internal medicine departments: the burden of a rising problem

Although internal medicine wards (IMWs) represent a significant reservoir of patients with candidemia, few investigators have specifically addressed the epidemiological aspects of candidaemia in this population. Of all patients hospitalized during the study period with candidaemia, 133/348 (38%) were admitted to IMWs. Variables associated with IMWs included: antibiotic therapy prior to hospitalization, urinary or central venous catheter, parenteral nutrition, tumour and age >75 years. Overall, 30-day mortality in IMWs was significantly higher than that in other wards (51.1% vs. 38.2%, p <0.02). Multiple logistic regression analysis identified the administration of antifungal treatment 48 h after having the first positive BC as an independent determinant of hospital mortality. Patients with candidaemia in IMWs account for a substantial proportion of patients with candidaemia and have higher mortality compared with patients in other wards.

Clinical and Therapeutic Aspects of Candidemia: A Five Year Single Centre Study

Background Candida is an important cause of bloodstream infections (BSI) in nosocomial settings causing significant mortality and morbidity. This study was performed to evaluate contemporary epidemiology, species distribution, antifungal susceptibility and outcome of candida BSI in an Italian hospital. Methods All consecutive patients who developed candidemia at Santa Maria della Misericordia University Hospital (Italy) between January 2009 and June 2014 were enrolled in the study. Results A total of 204 episodes of candidemia were identified during the study period with an incidence of 0.79 episodes/1000 admissions. C. albicans was isolated in 60.3% of cases, followed by C. parapsilosis (16.7%), C. glabrata (11.8%) and C. tropicalis (6.4%). Of all Candida BSI, 124 (60.8 %) occurred in patients admitted to IMW, 31/204 (15.2 %) in ICUs, 33/204 (16.2%) in surgical units and 16/204 (7.8%) in Hematology/Oncology wards. Overall, 47% of patients died within 30 days from the onset of candidemia. C. parapsilosis and C. glabrata candidemia were associated with the lowest mortality rate (36%), while patients with C. tropicalis BSI had the highest mortality rate (58.3%). Lower mortality rates were detected in patients receiving therapy within 48 hours from the time of execution of the blood cultures (57,1% vs 38,9%, P <0.05). At multivariate analysis, steroids treatment (OR= 0.27, p=0.005) and CVC removal (OR=3.77, p=0.014) were independently associated with lower and higher survival probability, respectively. Candidemia in patients with peripherally inserted central catheters (PICC) showed to be associated with higher mortality in comparison with central venous catheters (CVC, Short catheters and Portacath) and no CVC use. For each point increase of APACHE III score, survival probability decreased of 2%. Caspofungin (OR=3.45, p=0.015) and Amphothericin B lipid formulation (OR=15.26, p=0.033) were independently associated with higher survival probability compared with no treatment.

Tigecycline use in serious nosocomial infections: a drug use evaluation

BackgroundTigecycline is a novel antibiotic with activity against multidrug resistant bacteria. The aim of this study was to assess the efficacy of tigecycline use in serious hospital-acquired infections (HAI)Case presentationProspective observational study of tigecycline use was conducted in a 1500 beds university hospital. From January 1, 2007 and January 31, 2010, 207 pts were treated with tigecycline for the following indications: intra-abdominal, pneumonia, bloodstream and complicated skin and soft tissue infections and febrile neutropenia. The therapy was targeted in 130/207 (63%) and empirical in 77/207 (37%) patients. All bacteria treated were susceptible to tigecycline. Median duration of tigecycline therapy was 13 days (range, 6-28). Clinical success was obtained in 151/207 (73%) cases, with the highest success rate recorded in intra-abdominal infections [81/99 (82%)]. Microbiological success was achieved in 100/129 (78%) treated patients. Adverse clinical events were seen in 16/207 patients (7.7%):ConclusionsConsidering the lack of data on tigecycline for critically ill patients, we think that the reported data of our clinical experience despite some limitations can be useful for clinicians.

Novel β -lactam antibiotics and inhibitor combinations

Background: β-Lactam antibiotics are the most used antibacterial agents in clinical practice, but the development of resistance poses some questions about their future leading to an urgent requirement for new compounds. Specifically, β-lactamases represent the commonest single cause of bacterial resistance to β-lactam antibiotics. Numerous chromosomal and plasmid-mediated types are known and classified on the basis of their structure. Among them, extended-spectrum β-lactamases (ESBLs) and AmpC β-lactamase can confer broad-spectrum antibiotic resistance to ureidopenicillins, third-generation cephalosporins and aztreonam, posing unique therapeutic challenges. Furthermore, the spreading emergence of carbapenemases is a significant threat to the management of nosocomial infections. Objective: To review characteristics of new drugs for β-lactam resistance. Methods: We reviewed the principal characteristics of the new drugs studied for overcoming the emergence of β-lactam resistance among Gram-negative and Gram-positive pathogens. Results/conclusions: We included in our review new β-lactamase inhibitors (Ro 48-1220), non-β-lactam compounds (NXL-104), new oxapenenems (AM-112, -113, -114, -115) and penems (faropenem), new cephalosporins (ceftobiprole and ceftaroline) and new carbapenems (doripenem).

Current Status of Newer Carbapenems

OBJECTIVES Beta-lactam antibiotics represent the most commonly prescribed antibacterial agents. Since many bacteria have developed resistance to older agents, new beta-lactams have been introduced constantly. In the late 1970s, a new class of exceptionally broad-spectrum beta-lactams, the carbapenems, was identified. The carbapenems, such as the most popular imipenem and meropenem, have the widest spectra of antibacterial activity of all the beta-lactams and provide excellent coverage of many gram-negative and gram-positive aerobic and anaerobic bacteria. Despite the wide antibacterial spectrum, the carbapenems globally lack activity against Enterococcus faecium, methicillin-resistant Staphylococcus aureus (MRSA) and Stenotrophomonas maltophilia. METHODS We reviewed the principal characteristics of the novel carbapenems and their clinical implications. RESULTS AND CONCLUSIONS We included in our review: ertapenem, biapenem, panipenem, doripenem, tebipenem pivoxil and tomopenem.

New antibiotics and antimicrobial combination therapy for the treatment of gram-negative bacterial infections.

Purpose of reviewIncreasing rates of life-threatening infections due to multidrug-resistant (MDR) gram-negative bacteria, such as carbapenemase-producer strains, as well as pathogens that are resistant to all current therapeutic options, have been reported. The number of compounds that are currently being developed is still insufficient to control this global threat. We have reviewed the current available options for the treatment of MDR gram-negative infections, including combination regimens employing older antimicrobials and new compounds. Recent findingsA limited number of large trials have assessed the treatment options for commonly encountered resistant pathogens (e.g., Klebsiella pneumoniae, Acinetobacter baumanii, Pseudomonas aeruginosa). Antimicrobials that were used in the past, such as colistin and fosfomycin, have been recently resumed and used in association with carbapenems, tigecycline, or aminoglycosides, showing a positive impact on clinical outcomes. New compounds belonging to various antimicrobial classes (e.g. beta-lactamase inhibitors, cephalosporins, glycyclines, aminoglycosides) have been investigated. SummaryOnly few new molecules have an adequate activity against MDR gram-negative pathogens, especially carbapenemase-producer strains. Among these, ceftozolane/tazobactam has been recently approved for clinical use. Other compounds, such as avibactam combinations, plazomicin, and eravacycline, have shown promising activity in phase 2 and 3 clinical trials.