Estimating the association between antibiotic exposure and colonization with extended-spectrum ß-lactamase-producing Gram-negative bacteria using machine learning methods: a multicentre, prospective cohort study.

OBJECTIVES: The aim of the study was to measure the impact of antibiotic exposure on the acquisition of colonization with extended-spectrum ß-lactamase-producing Gram-negative bacteria (ESBL-GNB) accounting for individual- and group-level confounding using machine-learning methods. METHODS: Patients hospitalized between September 2010 and June 2013 at six medical and six surgical wards in Italy, Serbia and Romania were screened for ESBL-GNB at hospital admission, discharge, antibiotic start, and after 3, 7, 15 and 30 days. Primary outcomes were the incidence rate and predictive factors of new ESBL-GNB colonization. Random forest algorithm was used to rank antibiotics according to the risk of selection of ESBL-GNB colonization in patients not colonized before starting antibiotics. RESULTS: We screened 10 034 patients collecting 28 322 rectal swab samples. New ESBL-GNB colonization incidence with and without antibiotic treatment was 22/1000 and 9/1000 exposure-days, respectively. In the adjusted regression analyses, antibiotic exposure (hazard ratio (HR) 2.38; 95% CI 1.29-4.40), age 60-69 years (HR 1.19; 95% CI 1.05-1.34), and spring season (HR 1.25; 95% CI 1.14-1.38) were independently associated with new colonization. Monotherapy ranked higher als combination therapy in promoting ESBL-GNB colonization. Among monotherapy, cephalosporins ranked first followed by tetracycline (second), macrolide (fourth) and cotrimoxazole (seventh). Overall the ranking of cephalosporins was lower when used in combination. Among combinations not including cephalosporins, quinolones plus carbapenems ranked highest (eighth). Among sequential therapies, quinolones ranked highest (tenth) when prescribed within 30 days of therapy with cephalosporins. CONCLUSIONS: Impact of antibiotics on selecting ESBL-GNB at intestinal level varies if used in monotherapy or combination and according to previous antibiotic exposure. These finding should be explored in future clinical trials on antibiotic stewardship interventions. CLINICAL TRIAL REGISTRATION: NCT01208519.

Diabetic foot infections: a comprehensive overview.

Diabetic foot ulcers (DFUs), a micro-vascular complication, are associated with a substantial increase in morbidity and mortality. DFUs are a complicated mixture of neuropathy, peripheral arterial diseases, foot deformities, and infections. Foot infections are frequent and potentially devastating complications. Infection prospers in more than half of all foot ulcers and is the factor that most often leads to lower extremity amputation. The complications of microbial flora span the spectrum from superficial cellulitis to chronic osteomyelitis and gangrenous extremity lower limb amputations. Wounds without confirmed soft tissue or bone infections do not require antibiotic therapy. Mild and moderate infections need empiric therapy covering Gram-positive cocci, while severe infections caused by drug-resistant organisms require broad-spectrum anti-microbials targeting aggressive Gram-negative aerobes and obligate anaerobes.

A 72-h intervention for improvement of the rate of optimal antibiotic therapy in patients with bloodstream infections.

Antimicrobial stewardship programs are implemented to optimize the use of antibiotics and control the spread of antibiotic resistance. Many antimicrobial stewardship interventions have demonstrated significant efficacy in reducing unnecessary prescriptions of antibiotics, the duration of antimicrobial therapy, and mortality. We evaluated the benefits of a combination of rapid diagnostic tests and an active re-evaluation of antibiotic therapy 72 h after the onset of bloodstream infection (BSI). All patients with BSI from November 2015 to November 2016 in a 1100-bed university hospital in Rome, where an Infectious Disease Consultancy Unit (Unità di Consulenza Infettivologica, UDCI) is available, were re-evaluated at the bedside 72 h after starting antimicrobial therapy and compared to two pre-intervention periods: the UDCI was called by the ward physician for patients with BSI and the UDCI was called directly by the microbiologist immediately after a pathogen was isolated from blood cultures. Recommendations for antibiotic de-escalation or discontinuation significantly increased (54%) from the two pre-intervention periods (32% and 27.2%, p < 0.0001). Appropriate escalation also significantly increased (22.5%) from the pre-intervention periods (8.1% and 8.2%, p < 0.0001). The total duration of antibiotic therapy decreased with intervention (from 21.9 days [standard deviation, SD 15.4] in period 1 to 19.3 days [SD 13.3] in period 2 to 17.7 days in period 3 [SD 11.5]; p = 0.002) and the length of stay was significantly shorter (from 29.7 days [SD 29.3] in period 1 to 26.8 days [SD 24.7] in period 2 to 24.2 days in period 3 [SD 20.7]; p = 0.04) than in the two pre-intervention periods. Mortality was similar among the study periods (31 patients died in period 1 (15.7%), 39 (16.7%) in period 2, and 48 (15.3%) in period 3; p = 0.90). Rapid diagnostic tests and 72 h re-evaluation of empirical therapy for BSI significantly correlated with an improved rate of optimal antibiotic therapy and decreased duration of antibiotic therapy and length of stay.

Clinical and microbiological outcome in septic patients with extremely low 25-hydroxyvitamin D levels at initiation of critical care.

A relationship between vitamin D status and mortality in patients in intensive care units (ICU) has been documented. The present study aims to describe the clinical profile and sepsis-related outcome of critically ill septic patients with extremely low (<7 ng/mL) vitamin D levels at ICU admission. We conducted an observational study in the ICU of a teaching hospital including all patients admitted with severe sepsis/septic shock and undergoing 25-hydroxyvitamin D (25(OH)D) testing within the first 24 hours from admission. We studied 107 patients over 12 months. At ICU admission vitamin D deficiency (≤20 ng/mL) was observed in 93.5% of the patients: 57 (53.3%) showed levels <7 ng/mL. As primary outcome, sepsis-related mortality rate was higher in patients with vitamin D levels <7 ng/mL (50.9% versus 26%). Multivariate regression analysis showed that vitamin D concentration <7 ng/mL on ICU admission (p 0.01) and higher mean SAPS II (p <0.01) score were independent predictors of sepsis-related mortality. Patients with very low vitamin D levels suffered higher rate of microbiologically confirmed infections but a lower percentage of microbiological eradication with respect to patients whose values were >7 ng/mL (80.7% versus 58%, p 0.02; 35.3% versus 68%; p 0.03, respectively). Post hoc analysis showed that, in the extremely low vitamin D group, the 52 patients with pneumonia showed a longer duration of mechanical ventilation (9 days (3.75-12.5 days) versus 4 days (2-9 days), p 0.04) and the 66 with septic shock needed vasopressor support for a longer period of time (7 days (4-10 days) versus 4 days (2-7.25 days), p 0.02). Our results suggest that in critical septic patients extremely low vitamin D levels on admission may be a major determinant of clinical outcome. Benefits of vitamin D replacement therapy in this population should be elucidated.

Optimized Use of the MALDI BioTyper System and the FilmArray BCID Panel for Direct Identification of Microbial Pathogens from Positive Blood Cultures.

Despite the current reliance on blood cultures (BCs), the diagnosis of bloodstream infections (BSIs) can be sped up using new technologies performed directly on positive BC bottles. Two methods (the MALDI BioTyper system and FilmArray blood culture identification [BCID] panel) are potentially applicable. In this study, we performed a large-scale clinical evaluation (1,585 microorganisms from 1,394 BSI episodes) on the combined use of the MALDI BioTyper and FilmArray BCID panel compared to a reference (culture-based) method. As a result, the causative organisms of 97.7% (1,362/1,394) of the BSIs were correctly identified by our MALDI BioTyper and FilmArray BCID-based algorithm. Specifically, 65 (5.3%) out of 1,223 monomicrobial BCs that provided incorrect or invalid identifications with the MALDI BioTyper were accurately detected by the FilmArray BCID panel; additionally, 153 (89.5%) out of 171 polymicrobial BCs achieved complete identification with the FilmArray BCID panel. Conversely, full use of the MALDI BioTyper would have resulted in the identification of only 1 causative organism in 97/171 (56.7%) of the polymicrobial cultures. By applying our diagnostic algorithm, the median time to identification was shortened (19.5 h versus 41.7 h with the reference method; P < 0.001), and the minimized use of the FilmArray BCID panel led to a significant cost savings. Twenty-six out of 31 microorganisms that could not be identified were species/genera not designed to be detected with the FilmArray BCID panel, indicating that subculture was not dispensable for a few of our BSI episodes. In summary, the fast and effective testing of BC bottles is realistically adoptable in the clinical microbiology laboratory workflow, although the usefulness of this testing for the management of BSIs remains to be established.

Intraventricular versus intravenous colistin for the treatment of extensively drug resistant Acinetobacter baumannii meningitis.

BACKGROUND AND PURPOSE: Reports on the safety and efficacy of intraventricularly administered (IVT) colistin for the treatment of Acinetobacter baumannii ventriculomeningitis in adults are limited and no comparative studies of IVT colistin versus intravenous (IV) therapy alone have been published. This study compared outcomes of patients with postneurosurgical ventriculomeningitis caused by extensively drug-resistant A. baumannii treated with IV colistin or IV plus IVT colistin. METHODS: In an 11-year period, information on 18 consecutive patients with extensively drug-resistant A. baumannii ventriculomeningitis was collected. Infection was defined on the basis of (i) isolation of A. baumannii from the cerebrospinal fluid (CSF); (ii) laboratory evidence of CSF infection; (iii) signs/symptoms of central nervous system (CNS) infection. Patients were divided into group 1 (nine patients, IV colistin alone) and group 2 (nine patients, IV plus IVT colistin). RESULTS: Cerebrospinal fluid sterilization was documented for 12 of 18 patients (66.6%). The CSF sterilization rate was 33.3% in group 1 and 100% in group 2 (P = 0.009). The mean time to CSF sterilization was 21 days (range 8-48). Five patients died due to A. baumannii CNS infection (all in group 1), and five deaths were unrelated to A. baumannii ventriculomeningitis. Intensive care unit mean length of stay was shorter in group 2 (20.7 vs. 41.6 days, P = 0.046). Crude relative risk ratio of cumulative incidence of persistent CNS infection in group 1 versus group 2 was 13. No cases of chemical meningitis due to intrathecal colistin administration were encountered. CONCLUSIONS: Intraventricular colistin administration is much more effective than IV therapy alone and does not seem to add further toxicity.

Risk factors for bloodstream infections due to colistin-resistant KPC-producing Klebsiella pneumoniae: results from a multicenter case-control-control study.

The increasing prevalence of colistin resistance (ColR) Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae (Kp) is a matter of concern because of its unfavourable impact on mortality of KPC-Kp bloodstream infections (BSI) and the shortage of alternative therapeutic options. A matched case-control-control analysis was conducted. The primary study end point was to assess risk factors for ColR KPC-Kp BSI. The secondary end point was to describe mortality and clinical characteristics of these infections. To assess risk factors for ColR, 142 patients with ColR KPC-Kp BSI were compared to two controls groups: 284 controls without infections caused by KPC-Kp (control group A) and 284 controls with colistin-susceptible (ColS) KPC-Kp BSI (control group B). In the first multivariate analysis (cases vs. group A), previous colistin therapy, previous KPC-Kp colonization, ≥3 previous hospitalizations, Charlson score ≥3 and neutropenia were found to be associated with the development of ColR KPC-Kp BSI. In the second multivariate analysis (cases vs. group B), only previous colistin therapy, previous KPC-Kp colonization and Charlson score ≥3 were associated with ColR. Overall, ColR among KPC-Kp blood isolates increased more than threefold during the 4.5-year study period, and 30-day mortality of ColR KPC-Kp BSI was as high as 51%. Strict rules for the use of colistin are mandatory to staunch the dissemination of ColR in KPC-Kp-endemic hospitals.

Surveillance of bacterial and fungal infections in the postoperative period following liver transplantation: a series from 2005-2011.

Orthotopic liver transplantation (OLT) is a life-saving procedure for the treatment of many end-stage diseases, but infectious and acute rejection episodes remain major causes of morbidity and mortality. Bacterial and fungal infections can be due to intra-abdominal, biliary, respiratory, urinary, wound, central venous catheters (CVC) or unknown sources. Using the computerized database of our microbiology laboratory, we analyzed all the bacterial and fungal infections in the first three months following OLT among 151 consecutive adult recipients at single center between January 2005 and December 2011. Samples included blood, bile CVC, urine, and bronchoalveolar lavage (BAL) specimen. Culture and identification of the isolated microorganisms was done in accordance with standard microbiological procedures. Three hundred thirteen samples from the above sites showed positive results for gram-positive cocci (n = 137; 43.8%), gram-negative rods (n = 156; 49.8%), and Candida species (n = 19; 6.1%). One patient (0.3%) experienced a CVC-related infection caused by Fusarium oxysporum. Bacterial and particularly biliary tract infections seem to play major roles in morbidity and mortality in the first three months following OLT. The major contributors to patient morbidity and mortality were candidemia and/or invasive candidiasis mainly from the biliary tract and/or CVC-related infections.

Bacterial bloodstream infections in liver transplantation: etiologic agents and antimicrobial susceptibility profiles.

Liver transplantation (OLT) is a lifesaving procedure for the treatment of many end-stage liver diseases, but infection and acute rejection episodes still remain the main causes of morbidity and mortality. Bloodstream infections (BSIs), particularly, are the major cause of mortality among these patients. BSIs in OLT, are from intra-abdominal, biliary, respiratory, urinary, wound and/or central venous catheter sources. A certain percentage are of unknown origin. Using the computerized database of our microbiology laboratory, we analyzed all BSIs in 75 consecutive adult liver transplant patients in a single center between January 2008 and July 2011. BSIs occurred in 21/75 (28%) patients. Thirteen subjects had a single; two, two episodes, and the other six patients each >4 episodes. All episodes occurred in the first 60 days following OLT; the majority (74%), in the first month. Among 44 microorganisms recovered, 52.3% were gram-negative, the most frequent being Pseudomonas aeruginosa and Klebsiella pneumoniae; 47.7% were gram-positive, the most frequent being coagulase-negative staphylococci, particularly Staphylococcus epidermidis. Overall 65.9% of the isolates were resistant to several antibiotics: 40.9% displayed the multiding-resistant and 25% the panding-resistant phenotype. There was a high incidence of gram-negative and most importantly, resistant bacteria, which required appropriate therapy. These data showed that it is imperative to promote strategies to prevention and contain antimicrobial resistance.

Risk factors and mortality of healthcare-associated and community-acquired Staphylococcus aureus bacteraemia.

Staphylococcus aureus bacteraemia (SAB) is a leading cause of mortality and morbidity in both nosocomial and community settings. The objective of the study is to explore epidemiological characteristics and predisposing risk factors associated with healthcare-associated (HCA) and community-acquired (CA) SAB, and to evaluate any differences in mortality and efficacy of initial antimicrobial therapy on treatment outcome. We conducted a two-part analysis. First, a triple case-control study in which groups of HCA SAB with onset ≥ 48 h after hospital admission (HCA ≥ 48 h), HCA SAB with onset <48 h of hospital admission (HCA <48 h), and CA SAB were compared with controls. Second, a cohort study including all patients with SAB was performed to identify factors associated with in-hospital mortality. SAB was diagnosed in 165 patients over the study period (January 2007 to December 2007). Five variables were independently associated with HCA ≥ 48 h SAB: presence of central venous catheter, solid tumour, chronic renal failure, previous hospitalization and previous antibiotic therapy. Significant risk factors for HCA <48 h SAB were: Charlson Comorbidity Index ≥ 3, previous hospitalization, living in long-term care facilities and corticosteroid therapy. Factors independently associated with CA SAB were: diabetes mellitus, HIV infection and chronic live disease. Patients with HCA <48 h SAB were significantly more likely to receive initial inadequate antimicrobial treatment than patients with CA or HCA ≥ 48 h SAB (44.8% versus 33.3% and 31.5%, respectively). Logistic-regression analysis identified three variables as independent predictors of mortality: presentation with septic shock, infection with methicillin-resistant S. aureus, and initial inadequate antimicrobial treatment. More than half of patients with SAB have MRSA strains and presentation with septic shock, and inappropriate empirical therapy was associated with increased mortality.

Intestinal parasites isolated in a large teaching hospital, Italy, 1 May 2006 to 31 December 2008.

Intestinal parasites account for the majority of parasitic diseases, particularly in endemic areas. Most are transmitted via contaminated food. Because of increased immigration and travel, enteric parasitoses are now distributed worldwide. Between May 2006 and December 2008, we examined stool specimens from 5,351 patients (4,695 Italians, 656 non-Italians) for ova and parasites using microscopy, culture techniques, and molecular methods. Stools from 594 patients (11.1%) were contaminated and for all patients samples combined, a total of 700 intestinal parasites were counted. Ninety of the 594 infected patients had more than one parasite in their stools. Parasites causing intestinal disease occurred in 8.8% of patients. The prevalence was over twice as high among non-Italians (26.8% vs 8.9% in Italians, p<0.001) and higher in males (13.0% vs 9.5% in females, p=0.003). Most isolates were pathogenic protozoa, including in decreasing order of frequency: Blastocystis hominis, Giardia intestinalis, Entamoeba histolytica, and Cyclospora cayetanensis. The latter two species tended to be more common in Italians, although not at significant level (3.6% (15/418) vs 1.7% (3/176) in non-Italians, OR: 2.15; 95%CI: 0.60­11.70, p=0.22). Helminthes were found in 28 patients, mainly non-Italians (5.7% (10/176) vs 4.3% (18/418), OR: 1.34; 95%CI: 0.54­3.13, p=0.47). Ascaris lumbricoides and Hymenolepis nana were the most common. Strongyloides stercoralis, Enterobius vermicularis, Taenia spp. and Trichuris trichiura were also found. Intestinal parasites are a serious problem in developing countries, but should not be underestimated in industrialised countries.

Multidrug-resistant Pseudomonas aeruginosa bloodstream infections: risk factors and mortality.

We retrospectively studied patients diagnosed with P. aeruginosa bloodstream infections (BSIs) in two Italian university hospitals. Risk factors for the isolation of multidrug-resistant (MDR) or non-MDR P. aeruginosa in blood cultures were identified by a case-case-control study, and a cohort study evaluated the clinical outcomes of such infections. We identified 106 patients with P. aeruginosa BSI over the 2-year study period; 40 cases with MDR P. aeruginosa and 66 cases with non-MDR P. aeruginosa were compared to 212 controls. Independent risk factors for the isolation of MDR P. aeruginosa were: presence of central venous catheter (CVC), previous antibiotic therapy, and corticosteroid therapy. Independent risk factors for non-MDR P. aeruginosa were: previous BSI, neutrophil count <500/mm3, urinary catheterization, and presence of CVC. The 21-day mortality rate of all patients was 33·9%. The variables independently associated with 21-day mortality were presentation with septic shock, infection due to MDR P. aeruginosa, and inadequate initial antimicrobial therapy.

Tsukamurella tyrosinosolvens and Rhizobium radiobacter sepsis presenting with septic pulmonary emboli.

Septic pulmonary embolism (SPE) is an uncommon, but life-threatening event that is usually associated with extrapulmonary infections. We report the first case of bilateral SPE secondary to a central venous catheter-related bloodstream infection involving pathogens commonly considered environmental contaminants: Tsukamurella tyrosinosolvens and Rhizobium radiobacter. Empirical levofloxacin treatment was confirmed by in vitro susceptibility data and produced prompt clinical improvement, but removal of the infected line proved indispensable for eradication of the infection. Laboratory personnel should be aware of the pathogenic potential of these environmental organisms, particularly in immunocompromised hosts with indwelling catheters.

Evaluation of matrix-assisted laser desorption ionization-time-of-flight mass spectrometry in comparison to rpoB gene sequencing for species identification of bloodstream infection staphylococcal isolates.

As a result of variable expression of biochemical characters, misidentification by conventional phenotypic means often occurs with clinical isolates belonging to Staphylococcus species. Therefore, we evaluated the use of matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS) for the identification of 450 blood isolates of the most relevant staphylococcal species, using sequence analysis of the rpoB gene as the reference method. A correct species identification by MALDI-TOF was obtained in 99.3% (447/450), with only three isolates being misidentified. In addition, MALDI-TOF correctly identified all the staphylococcal subspecies studied, including Staphylococcus capitis subsp. capitis and subsp. urealyticus, Staphylococcus cohnii subsp. urealyticus, Staphylococcus hominis subsp. novobiosepticus and subsp. hominis, Staphylococcus saprophyticus subsp. saprophyticus, Staphylococcus schleiferi subsp. schleiferi and Staphylococcus sciuri subsp. sciuri. Thus, MALDI-TOF MS-based species identification of staphylococci can be routinely achieved without any substantial costs for consumables or the time needed for labour-intensive DNA sequence analysis.

Successful treatment of multidrug-resistant Acinetobacter baumannii ventriculitis with intrathecal and intravenous colistin.

Acinetobacter baumannii (AB) nosocomial infections, especially those due to multi-drug resistant (MDR) strains, are increasingly detected. We report a case of a 42-year-old male patient affected by low-grade ependymoma who developed AB-MDR post-neurosurgical ventriculitis. Initially, because of in vitro susceptibility, we used a combination of intravenous colistin and tigecycline. This treatment resulted in the improvement of the patient's initial condition. However, soon after, the infection relapsed; tigecycline was stopped and treatment with intrathecal colistin was initiated. Cure was achieved by continuing this treatment for approximately three weeks, without adverse effects.

Clonal dissemination of two clusters of Acinetobacter baumannii producing OXA-23 or OXA-58 in Rome, Italy.

Thirty consecutive Acinetobacter baumannii isolates producing carbapenem-hydrolysing oxacillinases, OXA-23 or OXA-58, were recovered from patients hospitalized in Rome, Italy, between January and November 2007. Among these isolates, two clones not associated with the European clones I or II were observed. The oxacillinase-encoding genes were plasmid- or chromosome-borne. This study reports the dissemination of carbapenem-resistant A. baumannii belonging to two clones among several units in a single hospital and emphasizes the ability of A. baumannii to cause epidemic/endemic outbreaks and also to acquire various resistance genes circulating in the hospital environment.

Vancomycin versus cefazolin prophylaxis for cerebrospinal shunt placement in a hospital with a high prevalence of meticillin-resistant Staphylococcus aureus.

International guidelines suggest that a high prevalence of meticillin-resistant Staphylococcus aureus (MRSA) infections should influence the use of vancomycin for surgical prophylaxis. In order to compare the efficacy and adverse effects of vancomycin versus cefazolin as antimicrobial prophylaxis for insertion of cerebrospinal fluid (CSF) shunts, a randomised prospective clinical trial was performed. Over a 16-month period, all consecutive adult patients who underwent CSF shunt insertion at a university hospital with a high prevalence of MRSA infections were included. Patients were randomly allocated to receive either vancomycin or cefazolin before surgery and followed-up for four weeks for the development of infections. Of the 176 patients included in the study, 88 received vancomycin and 88 cefazolin. Shunt infections were significantly less likely to be observed in patients who were on vancomycin prophylaxis (4% vs 14%; P=0.03). All isolated staphylococci were resistant to meticillin. Mortality of patients with post-surgical infections was higher in the cefazolin group (P=0.02). Our data suggest that use of vancomycin as prophylactic agent for cerebrospinal shunt placement reduces the rate of shunt infections in the context of high prevalence of MRSA.

Bacterial isolates from severe infections and their antibiotic susceptibility patterns in Italy: a nationwide study in the hospital setting.

The most frequent agents of severe bacterial infections and their antibiotic susceptibility patterns were determined in patients admitted to 45 Italian hospitals over the years 2002-2003. The most common diagnoses were: sepsis (33.8%), pneumonia (9.4%), intravascular catheter-associated infections (9.3%) and ventilator-associated pneumonia (8.1%). Overall, 5115 bacterial isolates were identified from 4228 patients. Three bacterial species, Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli, accounted for more than 50% of the isolates. Other prevalent bacterial isolates were Staphylococcus epidermidis and Enterococcus faecalis, while Acinetobacter baumanii ranked third among all Intensive Care Unit (ICU) isolates. 7% of S. aureus had intermediate resistance to vancomycin. Although E. faecalis displayed no vancomycin resistance, 34% of vancomycin-resistant isolates were found among Enterococcus faecium, one of the highest rates found to date, emphasizing the difference between these two enterococcal species. All the Gram-positive pathogens were susceptible to linezolid, with the exception of approximately 2% of the enterococcal isolates that were intermediate with a minimum inhibitory concentration (MIC)=4 microg/ml. Almost 10% of Escherichia coli, 14% of Klebsiella pneumoniae, 22% of Serratia marcescens and 50% of Enterobacter cloacae were non-susceptible to cefotaxime. Amikacin was the most active antibiotic against P. aeruginosa that showed lack of susceptibility to ceftazidime, gentamicin, piperacillin and ciprofloxacin ranging from 20 to 35%. Finally, Acinetobacter baumanii showed a high level of resistance to all the antibiotics tested including imipenem (58%). The results obtained in this study, the first of its kind in Italy, offer indications for guiding empirical therapy and implementing specific interventions to fight antibiotic-resistant bacterial infections and their transmission in the hospital setting in Italy.

Occurrence of extended-spectrum beta-lactamases in members of the family Enterobacteriaceae in Italy: implications for resistance to beta-lactams and other antimicrobial drugs.

An Italian nationwide survey was carried out to assess the prevalences and the antimicrobial susceptibilities of members of the family Enterobacteriaceae producing extended-spectrum beta-lactamases (ESBLs). Over a 6-month period, 8,015 isolates were obtained from hospitalized patients and screened for resistance to extended-spectrum cephalosporins and monobactams. On the basis of a synergistic effect between clavulanate and selected beta-lactams (ceftazidime, aztreonam, cefotaxime, cefepime, and ceftriaxone), 509 isolates were found to be ESBL positive (6.3%). Colony blot hybridization with bla(TEM) and bla(SHV) DNA probes allowed one to distinguish four different genotypes: TEM-positive, SHV-positive, TEM- and SHV-positive, and non-TEM, non-SHV ESBL types. MICs for each isolate (E-test) were obtained for widely used beta-lactams, combinations of beta-lactams with beta-lactamase inhibitors, aminoglycosides, and fluoroquinolones. Among ESBL-positive strains, Klebsiella pneumoniae, Proteus mirabilis, and Escherichia coli accounted for 73.6% of isolates. Overall, TEM-type ESBLs were more prevalent than SHV-type enzymes (234 versus 173), whereas the prevalence of strains producing both TEM- and SHV-type ESBLs was similar to that of isolates producing non-TEM, non-SHV enzymes (55 and 38, respectively). In vitro, all but one of the ESBL-producing isolates remained susceptible to imipenem. Susceptibility to other drugs varied: piperacillin-tazobactam, 91%; amoxicillin-clavulanic acid, 85%; cefoxitin, 78%; amikacin, 76%; ampicillin-sulbactam, 61%; ciprofloxacin, 58%; and gentamicin, 56%. Associated resistance to aminoglycosides and ciprofloxacin was observed most frequently among TEM-positive strains. Since therapeutic options for multiresistant Enterobacteriaceae are limited, combinations of beta-lactams and beta-lactamase inhibitors appear to represent an important alternative for treating infections caused by ESBL-producing ENTEROBACTERIACEAE:

Glycopeptide resistance among coagulase-negative staphylococci that cause bacteremia: epidemiological and clinical findings from a case-control study.

A 1-year prospective case-control study (ratio of control patients to case patients, 3:1) was performed to assess the incidence, risk factors, and genotypic patterns of bacteremia caused by glycopeptide-resistant coagulase-negative staphylococci (CoNS) and their correlation with hospital glycopeptide use. Among 535 subjects with CoNS bacteremia, 20 subjects had a glycopeptide-resistant strain (19 strains were resistant to teicoplanin and 1 was resistant to both teicoplanin and vancomycin). The percentage of resistant isolates recovered in 1 year was 8% in intensive care units and 3% and 2% in medical and surgical wards, respectively. Genotypic analysis of resistant strains showed different patterns with a high degree of polymorphism. Use of glycopeptides in individual wards was not statistically associated with the percentage of resistance. Previous exposure to beta-lactams and glycopeptides, multiple hospitalization in the previous year, and concomitant pneumonia were significantly associated with the onset of glycopeptide-resistant CoNS bacteremia. Mortality rates were 25% among case patients and 18% among control patients, and they were significantly higher among patients who presented with concomitant pneumonia and a high Acute Physiology and Chronic Health Evaluation III score.