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AbstractObjective:To assess the incidence of colonization and infection with carbapenemase-producing Enterobacteriaceae (CPE) and carbapenem-resistant Acinetobacter baumannii(CR-Ab) in the ICUs of our city hospitals before and during the coronavirus disease 2019 (COVID-19) pandemic.Methods:We conducted a multicenter, before-and-after, cross-sectional study to compare the rates of colonization and infection with CPE and/or CR-Ab in 2 study periods, period 1 (January–April 2019) and period 2 (January–April 2020). Incidence rate ratios (IRRs) and 95% confidence intervals (CIs) of weekly colonization and infection rates for each period were compared for the 2 study periods using Poisson regression. Weekly trends in the incidence of colonization or infection for each study period were summarized using local weighted (Loess) regression.Results:We detected no significant change in either IRR and weekly trend in CPE colonization and infection during the 2 study periods. A shift from KPC to other CPE mechanisms (OXA-48 and VIM) was observed during period 2. Compared to period 1, during period 2 the IRR of colonization and infection with CR-Ab increased 7.5- and 5.5-fold, respectively. Genome sequencing showed that all CR-Ab strains belonged to the CC92/IC2 clonal lineage. Clinical strains clustered closely into a single monophyletic group in 1 of the 3 centers, whereas they segregated in 2 different clusters in the other 2 centers, which strongly indicates horizontal transmission.Conclusions:Our findings indicate the need to conduct infection control activities targeted against the spread of antimicrobial resistance between and within hospitals during the COVID-19 pandemic, and if necessary, remodulating them according to the new organizational structures imposed by the pandemic.

Mixed vaginitis is defined as the simultaneous presence of at least two different vaginal pathogens, both contributing to an abnormal vaginal milieu leading to signs and symptoms. Pathogen coinfection occurs frequently in women with vaginitis, and both coinfection and mixed vaginitis have relevant clinical and therapeutic implications. Fenticonazole, an imidazole derivative with a broad spectrum of antimycotic and antimicrobial activity, appears at least as effective as other topical antifungals in the treatment of vulvovaginal candidiasis and can also have a major role in the treatment of mixed infections or coinfections of the lower genital tract. This paper will address the current role of topical fenticonazole as an empiric treatment of vulvovaginal infections, with a focus on the effectiveness in the treatment of mixed vaginitis and the possible implications of this.

•Dalbavancin treatment for deep sternal wound infection shows good clinical outcomes.•The long half-life of dalbavancin allows once-weekly dosing.•Dalbavancin treatment allows early discharge.

AbstractWe describe the high burden of carbapenemase-producing Enterobacteriaceae(CPE) colonization and infection in a neuro-rehabilitation hospital in Italy over a 6-year period. Overall, 9.3% of patients were found to be CPE carriers on admission; the rates of CPE in-hospital acquisition and CPE-BSI were 9.2 and 2.9 cases per 10,000 patient days, respectively.

OBJECTIVETo assess the impact of an antimicrobial stewardship program (ASP) on antibiotic consumption, Clostridium difficileinfections (CDI), and antimicrobial resistance patterns in a rehabilitation hospital.DESIGNQuasi-experimental study of the periods before (from January 2011 to June 2012) and after (from July 2012 to December 2014) ASP implementation.SETTING150-bed rehabilitation hospital dedicated to patients with spinal-cord injuries.INTERVENTIONBeginning in July 2012, an ASP was implemented based on systematic bedside infectious disease (ID) consultation and structural interventions (ie, revision of protocols for antibiotic prophylaxis and education focused on the appropriateness of antibiotic prescriptions). Antibiotic consumption, occurrence of CDI, and antimicrobial resistance patterns of selected microorganisms were compared between periods before and after the ASP implementation.RESULTSAntibiotic consumption decreased from 42 to 22 defined daily dose (DDD) per 100 patient days (P<.001). The main reductions involved carbapenems (from 13 to 0.4 DDD per 100 patient days; P=.01) and fluoroquinolones (from 11.8 to 0.99 DDD per 100 patient days; P=.006), with no increases in mortality or length of stay. The incidence of CDI decreased from 3.6 to 1.2 cases per 10,000 patient days (P=.001). Between 2011 and 2014, the prevalence of extensively drug-resistant (XDR) strains decreased from 55% to 12% in P. aeruginosa(P<.001) and from 96% to 73% in A. baumannii(P=.03). The prevalence of ESBL-producing strains decreased from 42% to 17% in E. coli(P=.0007) and from 62% to 15% in P. mirabilis(P=.0001). In K. pneumoniae,the prevalence of carbapenem-resistant strains decreased from 42% to 17% (P=.005), and the prevalence of in methicillin-resistant S. aureusstrains decreased from 77% to 40% (P<.0008).CONCLUSIONSAn ASP based on ID consultation was effective in reducing antibiotic consumption without affecting patient outcomes and in improving antimicrobial resistance patterns in a rehabilitation hospital.Infect Control Hosp Epidemiol.2016;1–7

Multidrug resistance associated with extended-spectrum beta-lactamase (ESBL) and Klebsiella pneumoniaecarbapenemase (KPC) among K. pneumoniaeis endemic in southern Europe. We retrospectively analyzed the impact of resistance on the appropriateness of empirical therapy and treatment outcomes of K. pneumoniaebloodstream infections (BSIs) during a 2-year period at a 1420-bed tertiary-care teaching hospital in northern Italy. We identified 217 unique patient BSIs, including 92 (42) KPC-positive, 49 (23) ESBL-positive, and 1 (0.5) metallo-beta-lactamase-positive isolates. Adequate empirical therapy was administered in 74 of infections caused by non-ESBL non-KPC strains, versus 33 of ESBL and 23 of KPC cases (p < 0.0001). To clarify the impact of resistance on BSI treatment outcomes, we compared several different models comprised of non-antibiotic treatment-related factors predictive of patients’ 30-day survival status. Acute Physiology and Chronic Health Evaluation (APACHE) II score determined at the time of positive blood culture was superior to other investigated models, correctly predicting survival status in 83 of the study cohort. In multivariate analysis accounting for APACHE II, receipt of inadequate empirical therapy was associated with nearly a twofold higher rate of death (adjusted hazard ratio 1.9, 95 confidence interval 1.1–3.4; p = 0.02). Multidrug-resistant K. pneumoniaeaccounted for two-thirds of all K. pneumoniaeBSIs, high rates of inappropriate empirical therapy, and twofold higher rates of patient death irrespective of underlying illness.

ABSTRACTThe production of Klebsiella pneumoniaecarbapenemases (KPCs) by Enterobacteriaceaehas become a significant problem in recent years. To identify factors that could predict isolation of KPC-producing K. pneumoniae(KPCKP) in clinical samples from hospitalized patients, we conducted a retrospective, matched (1:2) case-control study in five large Italian hospitals. The case cohort consisted of adult inpatients whose hospital stay included at least one documented isolation of a KPCKP strain from a clinical specimen. For each case enrolled, we randomly selected two matched controls with no KPCKP-positive cultures of any type during their hospitalization. Matching involved hospital, ward, and month/year of admission, as well as time at risk for KPCKP isolation. A subgroup analysis was also carried out to identify risk factors specifically associated with true KPCKP infection. During the study period, KPCKP was isolated from clinical samples of 657 patients; 426 of these cases appeared to be true infections. Independent predictors of KPCKP isolation were recent admission to an intensive care unit (ICU), indwelling urinary catheter, central venous catheter (CVC), and/or surgical drain, ≥2 recent hospitalizations, hematological cancer, and recent fluoroquinolone and/or carbapenem therapy. A Charlson index of ≥3, indwelling CVC, recent surgery, neutropenia, ≥2 recent hospitalizations, and recent fluoroquinolone and/or carbapenem therapy were independent risk factors for KPCKP infection. Models developed to predict KPCKP isolation and KPCKP infection displayed good predictive power, with the areas under the receiver-operating characteristic curves of 0.82 (95% confidence interval [CI], 0.80 to 0.84) and 0.82 (95% CI, 0.80 to 0.85), respectively. This study provides novel information which might be useful for the clinical management of patients harboring KPCKP and for controlling the spread of this organism.

We report our clinical experience with the use of daptomycin, administered in the dosage of 8 mg/kg/d in 3 minutes, in treating 12 critically ill children younger than 12 years, with bloodstream infections (n = 9) and complicated skin and soft-tissue infections (n = 3). Mean treatment duration was 14 ± 5 days; microbiologic eradication was achieved in all patients, and no drug related adverse events occurred.

We determined the in vitroactivity of fenticonazole against 318 vaginitis isolates of Candidaand bacterial species and selected 28 isolates for time-kill studies. At concentrations equal to 4× MIC, fenticonazole reached the 99.9% killing endpoint by ∼10 h for Staphylococcus aureus, Streptococcus agalactiae, and Escherichia coliand by ∼17 h for Candida albicansand Candida parapsilosis; and at concentrations equal to 8× MIC, by ∼19 and ∼20 h for Candida glabrataand Candida tropicalis, respectively.

Invasive fungal infections, particularly invasive aspergillosis (IA), are frequent complications in immunocompromised patients. The identification of risk factors for IA is crucial to select patients who will benefit from different antifungal treatment. Retrospectively, we studied 1,194 hospitalizations registered at our Institution between March 2005 and December 2007, involving 618 patients affected by haematological malignancies (acute leukemia 34%, lymphoma 34%, multiple myeloma 24%, chronic myeloid leukemia 5%, severe aplastic anemia 1.5%, chronic lymphocytic leukemia 1.5%), with the purpose of developing a risk score able to stratify patients in categories at different risk for IA. Every febrile episode and every hospitalization without febrile episodes were recorded as single “phase”, for a total number of 1,409 “phases”. In 53% of the phases, the haematological malignancy was fully active (first presentation or resistant disease), and the main treatments administrated were: induction chemotherapy (18%), consolidation chemotherapy (20%), salvage chemotherapy (15%), HSCT in 33% (autologous: 21%; allogeneic: 12%). In 13% of the hospitalizations, patients did not receive chemotherapy but supportive cares. Seventeen variables were assessed as risk factors for IA according to literature data and to local clinical practice (age, smoking habit, type of job, previous IA, prolonged steroids treatment, diabetes, type of haematological malignancy, disease staus, type of treatment, prolonged neutropenia and lymphocytopenia, acute or chronic GvHD, CMV infection, mucositis, presence or absence of HEPA filter, proximity of building sites to the Haematology Unit) receiving a score ranging from 0 to 2. Summing the weighted points assigned to each variable, a total score (TSCORE08) was calculated for each phase and allowed to empirically identify 3 groups of patients at low (1 to 8), intermediate (8.5 to 11.5), and high (12 to 17) risk for IA, and was significantly higher in patients with IA (p < 0.001). Nine variables resulted to correlated significantly with IA in univariate analysis and were entered into the logistic regression analysis and 4 of them (type of job, lymphocytopenia, disease status, prolonged severe neutropenia) maintained their prognostic significance, allowing to derive, for each phase, a new score (BoSCORE08), which was also significantly higher in patients with IA (p < 0.001). The Areas Under the Curve derived from the TSCORE08 and the BoSCORE08 were equivalent, but the BoSCORE08 significantly reduced the number of variables taken into consideration. Adopting 5 as cut-off value for BoSCORE08, the model showed a high Negative Predictive value, a sensitivity of 0.950 (38/40) and a specificity of 0.545 (623/1,369), with a diagnostic Odds Ratio of around 22, which indicates that the risk of experiencing an IA in a patient with high BoSCORE08 was around 22 times higher than that of a patient with a low BoSCORE08. In conclusion, BoSCORE08 may contribute to optimize the management of patients at high risk for IA, improving the outcome, reducing the toxicity and the costs related to the use of antifungal agents in patients with haematological malignancies.

Invasive fungal infections, particularly invasive aspergillosis (IA), are frequent complications in immunocompromised patients. The identification of risk factors for IA is crucial to select patients who will benefit from different antifungal treatment. Retrospectively, we studied 1,194 hospitalizations registered at our Institution between March 2005 and December 2007, involving 618 patients affected by haematological malignancies (acute leukemia 34%, lymphoma 34%, multiple myeloma 24%, chronic myeloid leukemia 5%, severe aplastic anemia 1.5%, chronic lymphocytic leukemia 1.5%), with the purpose of developing a risk score able to stratify patients in categories at different risk for IA. Every febrile episode and every hospitalization without febrile episodes were recorded as single “phase”, for a total number of 1,409 “phases”. In 53% of the phases, the haematological malignancy was fully active (first presentation or resistant disease), and the main treatments administrated were: induction chemotherapy (18%), consolidation chemotherapy (20%), salvage chemotherapy (15%), HSCT in 33% (autologous: 21%; allogeneic: 12%). In 13% of the hospitalizations, patients did not receive chemotherapy but supportive cares. Seventeen variables were assessed as risk factors for IA according to literature data and to local clinical practice (age, smoking habit, type of job, previous IA, prolonged steroids treatment, diabetes, type of haematological malignancy, disease staus, type of treatment, prolonged neutropenia and lymphocytopenia, acute or chronic GvHD, CMV infection, mucositis, presence or absence of HEPA filter, proximity of building sites to the Haematology Unit) receiving a score ranging from 0 to 2. Summing the weighted points assigned to each variable, a total score (TSCORE08) was calculated for each phase and allowed to empirically identify 3 groups of patients at low (1 to 8), intermediate (8.5 to 11.5), and high (12 to 17) risk for IA, and was significantly higher in patients with IA (p<0.001). Nine variables resulted to correlated significantly with IA in univariate analysis and were entered into the logistic regression analysis and 4 of them (type of job, lymphocytopenia, disease status, prolonged severe neutropenia) maintained their prognostic significance, allowing to derive, for each phase, a new score (BoSCORE08), which was also significantly higher in patients with IA (p<0.001). The Areas Under the Curve derived from the TSCORE08 and the BoSCORE08 were equivalent, but the BoSCORE08 significantly reduced the number of variables taken into consideration. Adopting 5 as cut-off value for BoSCORE08, the model showed a high Negative Predictive value, a sensitivity of 0.950 (38/40) and a specificity of 0.545 (623/1,369), with a diagnostic Odds Ratio of around 22, which indicates that the risk of experiencing an IA in a patient with high BoSCORE08 was around 22 times higher than that of a patient with a low BoSCORE08. In conclusion, BoSCORE08 may contribute to optimize the management of patients at high risk for IA, improving the outcome, reducing the toxicity and the costs related to the use of antifungal agents in patients with haematological malignancies.