Clinical effectiveness of cefiderocol for the treatment of bloodstream infections due to carbapenem-resistant Acinetobacter baumannii during the COVID-19 era: a single center, observational study.

BACKGROUND: We assessed the clinical effectiveness of cefiderocol (CFDC) in comparison with colistin (COL) for the treatment of carbapenem-resistant Acinetobacter baumannii (CRAB) bloodstream infections (BSI). MATERIALS/METHODS: Retrospective cohort study including adults with CRAB-BSI. Outcomes were mortality, clinical cure and adverse events during therapy. The average treatment effect of CFDC compared to COL was weighted with the inverse-probability treatment weight (IPTW). RESULTS: Overall, 104 patients were included (50 CFDC, 54 COL), median age 66.5 years, median Charlson Comorbidity Index 5, septic shock in 33.6% of patients. Primary BSI accounted for 43.3% of cases, followed by ventilator-associated pneumonia (VAP) (26%), catheter-related BSI (20.2%) and hospital-acquired pneumonia (HAP) (9.6%). Although not significantly, mortality at all time points was lower for CFDC than COL, while clinical cure was higher in CFDC than COL (66% vs. 44.4%, p = 0.027). Adverse events were more frequent in COL than CFDC-group (38.8% vs. 10%, p < 0.0001), primarily attributed to acute kidney injury (AKI) in the COL group. Patients with bacteremic HAP/VAP treated with CFDC had a significant lower 30-d mortality and higher clinical cure than COL (p = 0.008 and p = 0.0008, respectively). Increment of CCI (p = 0.005), ICU (p = 0.025), SARS-CoV2 (p = 0.006) and ECMO (p < 0.0001) were independently associated with 30-d mortality, while receiving CFDC was not associated with survival. CONCLUSIONS: CFDC could represent an effective and safe treatment option for CRAB BSI, especially in patients with bacteremic HAP/VAP and frail patients where the risk of acute renal failure during therapy should be avoided.

Clinical course of Coronavirus Disease-19 in patients with haematological malignancies is characterized by a longer time to respiratory deterioration compared to non-haematological ones: results from a case-control study.

BACKGROUND: We evaluated clinical features and risk factors for mortality in patients with haematological malignancies and COVID-19. METHODS: Retrospective, case-control (1:3) study in hospitalized patients with COVID-19. Cases were patients with haematological malignancies and COVID-19, controls had COVID-19 without haematological malignancies. Patients were matched for sex, age and time of hospitalization. RESULTS: Overall, 66 cases and 198 controls were included in the study. Cases had higher prior corticosteroid use, infection rates, thrombocytopenia and neutropenia and more likely received corticosteroids and antibiotics than controls. Cases had higher respiratory deterioration than controls (78.7% vs 65.5%, p = 0.04). Notably, 29% of cases developed respiratory worsening > 10 days after hospital admission, compared to only 5% in controls. Intensive Care Unit admission and mortality were higher in cases than in controls (27% vs 8%, p = 0.002, and 35% vs 10%, p < 0.001). At multivariable analysis, having haematological malignancy [OR4.76, p < 0.001], chronic corticosteroid therapy [OR3.65, p = 0.004], prior infections [OR57.7, p = 0.006], thrombocytopenia [OR3.03, p < 0.001] and neutropenia [OR31.1, p = 0.001], low albumin levels [OR3.1, p = 0.001] and ≥ 10 days from hospital admission to respiratory worsening [OR3.3, p = 0.002] were independently associated with mortality. In cases, neutropenia [OR3.1, p < 0.001], prior infections [OR7.7, p < 0.001], ≥ 10 days to respiratory worsening [OR4.1, p < 0.001], multiple myeloma [OR1.5, p = 0.044], the variation of the CT lung score during hospitalization [OR2.6, p = 0.006] and active treatment [OR 4.4, p < 0.001] all were associated with a worse outcome. CONCLUSION: An underlying haematological malignancy was associated with a worse clinical outcome in COVID-19 patients. A prolonged clinical monitoring is needed, since respiratory worsening may occur later during hospitalization.

Comparison of clinical features and outcomes in COVID-19 and influenza pneumonia patients requiring intensive care unit admission.

BACKGROUND: Little is known in distinguishing clinical features and outcomes between coronavirus disease-19 (COVID-19) and influenza (FLU). MATERIALS/METHODS: Retrospective, single-centre study including patients with COVID-19 or FLU pneumonia admitted to the Intensive care Unit (ICU) of Policlinico Umberto I (Rome). Aims were: (1) to assess clinical features and differences of patients with COVID-19 and FLU, (2) to identify clinical and/or laboratory factors associated with FLU or COVID-19 and (3) to evaluate 30-day mortality, bacterial superinfections, thrombotic events and invasive pulmonary aspergillosis (IPA) in patients with FLU versus COVID-19. RESULTS: Overall, 74 patients were included (19, 25.7%, FLU and 55, 74.3%, COVID-19), median age 67 years (58-76). COVID-19 patients were more male (p = 0.013), with a lower percentage of COPD (Chronic Obstructive Pulmonary Disease) and chronic kidney disease (CKD) (p = 0.001 and p = 0.037, respectively) than FLU. SOFA score was higher (p = 0.020) and lymphocytes were significantly lower in FLU than in COVID-19 [395.5 vs 770.0 cells/mmc, p = 0.005]. At multivariable analysis, male sex (OR 6.1, p < 0.002), age > 65 years (OR 2.4, p = 0.024) and lymphocyte count > 725 cells/mmc at ICU admission (OR 5.1, p = 0.024) were significantly associated with COVID-19, whereas CKD and COPD were associated with FLU (OR 0.1 and OR 0.16, p = 0.020 and p < 0.001, respectively). No differences in mortality, bacterial superinfections and thrombotic events were observed, whereas IPA was mostly associated with FLU (31.5% vs 3.6%, p = 0.0029). CONCLUSIONS: In critically ill patients, male sex, age > 65 years and lymphocytes > 725 cells/mmc are related to COVID-19. FLU is associated with a significantly higher risk of IPA than COVID-19.

Co-infection of SARS-CoV-2 with Chlamydia or Mycoplasma pneumoniae: a case series and review of the literature.

INTRODUCTION: The novel coronavirus SARS-CoV-2 has spread all over the world causing a global pandemic and representing a great medical challenge. Nowadays, there is limited knowledge on the rate of co-infections with other respiratory pathogens, with viral co-infection being the most representative agents. Co-infection with Mycoplasma pneumoniae has been described both in adults and pediatrics whereas only two cases of Chlamydia pneumoniae have been reported in a large US study so far. METHODS: In the present report, we describe a series of seven patients where co-infection with C. pneumoniae (n = 5) or M. pneumoniae (n = 2) and SARS-CoV-2 was detected in a large teaching hospital in Rome. RESULTS AND CONCLUSION: An extensive review of the updated literature regarding the co-infection between SARS-CoV-2 and these atypical pathogens is also performed.

Multimodal surveillance of healthcare associated infections in an intensive care unit of a large teaching hospital

BACKGROUND: Healthcare-associated infections (HAIs), or nosocomial infections, represent a significant burden in terms of mortality, morbidity, length of stay and costs for patients hospitalized in intensive care units (ICUs). Surveillance systems are recommended by national and international institutions to gather data on HAIs in order to develop and evaluate interventions that reduce the risk of HAIs. STUDY DESIGN: Here we describe the methodology and the results of the surveillance system implemented in the ICU of the Policlinico Umberto I, a large teaching hospital in Rome, from April 2016 to October 2018. METHODS: The multimodal infection surveillance system integrates four different approaches: i) active surveillance of inpatients; ii) environmental microbiological surveillance; iii) surveillance of isolated microorganisms; and iv) behavioral surveillance of healthcare personnel. Data were collected on catheter-related bloodstream infections, ventilation-associated pneumonia, catheter-associated urinary tract infections and primary bloodstream infections that developed in patients after 48 h in the ICU. For environmental surveillance 14 points were selected for sampling (i.e. bed edges, medication carts, PC keyboards, sink faucets). The system of active surveillance of HAIs also included surveillance of microorganisms, consisting of the molecular genotyping of bacterial isolates by pulsed-field gel electrophoresis (PFGE). From 1 November 2016, monitoring of compliance with guidelines for hand hygiene (HH) and proper glove or gown use by healthcare personnel was included in the surveillance system. After the first six months (baseline phase), a multimodal intervention to improve adherence to guidelines by healthcare personnel was conducted with the ICU staff. RESULTS: Overall, 773 patients were included in the active surveillance. The overall incidence rate of device-related HAIs was 14.1 (95% CI: 12.2-16.3) per 1000 patient-days. The monthly device-related HAI incident rate showed a decreasing trend over time, with peaks of incidence becoming progressively lower. The most common bacterial isolates were Klebsiella pneumoniae (20.7%), Acinetobacter baumannii (17.2%), Pseudomonas aeruginosa (13.4%) and Staphylococcus aureus (5.4%). Acinetobacter baumannii and Klebsiella pneumoniae showed the highest proportion of isolates with a multidrug-resistant profile. A total of 819 environmental samples were collected, from which 305 bacterial isolates were retrieved. The most frequent bacterial isolates were Acinetobacter baumannii (27.2%), Staphylococcus aureus (12.1%), Enterococcus faecalis (11.1%), Klebsiella pneumoniae (5.2%) and Pseudomonas aeruginosa (4.7%). All Acinetobacter baumannii, Pseudomonas aeruginosa and Klebsiella pneumoniae environmental isolates were at least multidrug-resistant. Genotyping showed a limited number of major PFGE patterns for both clinical and environmental isolates of Klebsiella pneumoniae and Acinetobacter baumannii. Behavioral compliance rates significantly improved from baseline to post-intervention phase. CONCLUSIONS: By integrating information gathered from active surveillance, environmental microbiological surveillance, surveillance of bacterial isolates and behavioral surveillance of healthcare personnel, the multimodal infection surveillance system returned a precise and detailed view of the infectious risk and microbial ecology of the ICU.

Role of biomarkers in adult sepsis and their application for a good laboratory practice: a pilot study.

This study measured Procalcitonin (PCT), Presepsin (PRE-S) and pro-Adrenomedullin (pro-ADM) in intensive care unit (ICU) patient’s blood to assess their contribution to accurate diagnosis of sepsis and potential predictive impact on prognosis. The final aim was to improve the use of infection biomarkers for optimizing the impact of laboratory medicine on clinical outcomes, focusing on the good management of resources designed to produce maximum effectiveness and efficiency. Sixty-four adult patients were studied during their hospitalization in ICU; blood samples were collected and categorized according to their clinical diagnosis and illness severity, and sepsis marker levels were measured on automated immunoassay platforms. PCT, PRE-S and pro-ADM infection markers were significantly lower in controls than in sepsis or septic shock groups. The area under the curve, by ROC curve analysis, was 0.945 for PCT, 0.756 for PRE-S and 0.741 for pro-ADM. Sepsis diagnostic accuracy was not improved by combining PCT, PRE-S and pro-ADM measures. Preliminary data demonstrated that, despite PRE-S and pro-ADM being able to differentiate between septic and non-septic patients with accuracy, PCT remains the most reliable marker available. The results obtained still do not allow us to consider a combination of markers, because it would merely increase laboratory costs without improving diagnostic performance. Furthermore, the results confirm a possible prognostic role of pro-ADM in septic states, but no correlation between biomarker levels and survival at 48 h was detected. Hence PCT, PRE-S, nor pro-ADM can be used to predict short-term prognosis.

A cluster of fulminant Clostridium difficile colitis in an intensive care unit in Italy.

We describe, for the first time, a cluster of lethal fulminant health-care associated Clostridium difficile (CD) colitis in Italy, observed in the intensive care unit (ICU) of an Italian tertiary care hospital in Rome. For all cases the cause of ICU admission was CD-related septic shock. Three out of seven patients were residents in a long-term care facility in Rome, and the others had been transferred to the ICU from different medical wards of the same hospital. Five patients died within 96 h of ICU admission. Because of a clinical deterioration after 4 days of adequate antibiotic therapy, two patients underwent subtotal colectomy: both of them died within 30 days of surgical intervention. In four cases, ribotyping assay was performed and ribotype 027 was recognized. This high mortality rate could be attributable to three findings: the extent of disease severity induced by the strain 027, the delay in antimicrobial therapy administration, and the lack of efficacy of the standard antibiotic treatment for fulminant CD colitis compared to an earlier surgical approach. In order to contain a CD infection epidemic, control and surveillance measures should be implemented, and empirical therapy should be administered. Because of potential 027 ribotype CD spread in Italy, CDI should be regarded with a high index of suspicion in all patients presenting with shock and signs or symptoms suggesting abdominal disease, and an early surgical approach should be considered.

SIMIFF study: Italian fungal registry of mold infections in hematological and non-hematological patients.

PURPOSE: We compared the risk factors, the diagnostic tools and the outcome of filamentous fungal infections (FFIs) in hematological patients (HAEs) and non-hematological patients (non-HAEs). METHODS: Prospective surveillance (2009-2011) of proven and probable FFIs was implemented in 23 Italian hospitals. RESULTS: Out of 232 FFIs, 113 occurred in HAEs and 119 in non-HAEs. The most frequent infection was invasive aspergillosis (76.1 % for HAEs, 56.3 % for non-HAEs), and the localization was principally pulmonary (83.2 % for HAEs, 74.8 % for non-HAEs). Neutropenia was a risk factor for 89.4 % HAEs; the main underlying condition was corticosteroid treatment (52.9 %) for non-HAEs. The distribution of proven and probable FFIs was different in the two groups: proven FFIs occurred more frequently in non-HAEs, whereas probable FFIs were correlated with the HAEs. The sensitivity of the galactomannan assay was higher for HAEs than for non-HAEs (95.3 vs. 48.1 %). The overall mortality rate was 44.2 % among the HAEs and 35.3 % among the non-HAEs. The etiology influenced the patient outcomes: mucormycosis was associated with a high mortality rate (57.1 % for HAEs, 77.8 % for non-HAEs). CONCLUSIONS: The epidemiological and clinical data for FFIs were not identical in the HAEs and non-HAEs. The differences should be considered to improve the management of FFIs according to the patients' setting.

Role of empirical and targeted therapy in hospitalized patients with bloodstream infections caused by ESBL-producing Enterobacteriaceae.

BACKGROUND: Bloodstream infection (BSI) due to extended-spectrum ß-lactamase (ESBL) producing Enterobacteriaceae are a major cause of in-hospital mortality. The effect on survival of empirical and targeted antibiotic therapy in these patients remains controversial. METHODS: A prospective cohort study was conducted analyzing data from 94 patients (age 59 ± 21 years) with BSI due to ESBL producing strains (Sixty-one E. coli, 26 K. pneumoniae, 4 Proteus spp and 3 Enterobacter spp). RESULTS: Risk factors associated with 21-day mortality at univariate analysis were: recent administration of antibiotic therapy (p=0.049), higher SOFA score (p=0.05), ICU stay (p <0.01), hypotension at presentation (p =0.001) or septic shock (p <0.001) and bacteremia from source other than urinary tract (p=0.03). Regardless of antibiotic class used, no differences in survival were noted between patients receiving or not adequate initial antimicrobial treatment (37.1% vs 23.7% p=0.23); on the other hand, compared with the administration of other in vitro active antibiotics, the use of carbapenem as definitive therapy was associated with a significantly lower 21-day mortality (54.3% vs 28.5% p=0.02). CONCLUSIONS: These findings suggest that the administration of an adequate initial therapy is not associated with mortality in hospitalized patients with BSI due to Enterobacteriaceae. The severity of clinical conditions at presentation and the administration of carbapenems as definitive therapy seems to be really important in affecting the outcome of patients with BSI due to ESBL producing strains.

Patient risk factors for outer membrane permeability and KPC-producing carbapenem-resistant Klebsiella pneumoniae isolation: results of a double case-control study.

BACKGROUND: In the 1,200-bed university hospital "Umberto I" in Rome, Italy, we observed a dramatic substitution of a precedingly well-documented Klebsiella pneumoniae clone (ST37) with ertapenem resistance by outer membrane permeability modification (Porin-ER-Kp) with a new K. pneumoniae strain expressing carbapenem resistance due to K. pneumoniae carbapenemase production (KPC-CR-Kp). A case-case-control study was carried out to evaluate risk factors for Porin-ER-Kp and KPC-CR-Kp isolation. METHODS: All patients with hospital-acquired K. pneumoniae isolation between July 2008 and June 2011 were included. Two case groups including patients harbouring KPC-CR-Kp and Porin-ER-Kp were analysed, with a third control group from whom carbapenem-susceptible K. pneumoniae (CS-Kp) were isolated. RESULTS: Forty-four KPC-CR-Kp cases, 39 Porin-ER-Kp cases and 60 CS-Kp controls were analysed. During the 3-year study, a specific Porin-ER-Kp endemic clone (ST37) was substituted by a new KPC-CR-Kp clone (ST512). Breakthrough bacteraemias occurred in 21 out of 26 KPC-CR-Kp group bloodstream infections (BSIs); nine of these developed during carbapenem therapy and seven with colistin and/or tigecycline therapy. In 13 Porin-ER-Kp BSIs, breakthrough bacteraemias developed in eight patients and four during carbapenem therapy. In the multivariable analysis, KPC-CR-Kp isolates were associated with carbapenems [odds ratio (OR) 7.74; 95 % confidence interval (CI) 1.70-35.2; p < 0.01) and endoscopy (OR 6.71; 95 % CI 1.25-36.0; p < 0.03). Porin-ER-Kp independent risk factors included second-generation cephalosporins (OR 25.7; 95 % CI 3.20-206.8; p < 0.01), carbapenems (OR 19.1; 95 % CI 4.34-83.9; p < 0.001), acute renal failure (OR 7.17; 95 % CI 1.33-38.6; p < 0.03), endoscopy (OR 6.12; 95 % CI 1.46-25.6; p < 0.02) and third-generation cephalosporins (OR 5.3; 95 % CI 1.34-20.9; p < 0.02). CONCLUSIONS: Porin-ER-Kp strains needed major antimicrobial pressure compared to KPC-CR-Kp to express resistance. KPC-CR-Kp substituted Porin-ER-Kp strains, causing more infections. KPC-CR-Kp breakthrough bacteraemia occurred even under therapy with tigecycline or colistin, underlining that an antibiotic stewardship programme is needed urgently.

Candidemia in Neurosurgical Intensive Care Unit: preliminary analysis of the effect of topical Nystatin prophylaxis and adequate source control on patients with early tracheostomy intubation.

INTRODUCTION: The present study represents a preliminary evaluation of the impact of topical nystatin prophylaxis administration and adequate CVC management on reducing the chance of developing candidemia in neurosurgical intensive care unit (NICU) patients. MATERIALS AND METHODS: We conducted a case-control study at the nine bed NICU of the Policlinico "Umberto I" teaching hospital in Rome, Italy, during the period from January 2011 to July 2012. We compared eight patients with culture proven Candida bloodstream infection (CBSI) with a control group of 19 patients who did not have evidence of CBSI. RESULTS: When the CBSI group was compared with the control group, the former were more likely than controls to not have received nystatin prophylaxis and adequate catheter care (p= 0,008). When CBSI group was matched with patients with no adequate source control and nystatin prophylaxis, average NICU stay (71.13 days vs 19.0 days) was significant (mean difference = -52.12 days, 95% CI -97.11 to -7.14, p= 0.028). The same was true for mean time of glucocorticoid exposure (mean difference = -10.5 days, 95% CI -17.35 to -3.65, p<0.01). Binary logistic regression analysis demonstrated no significant association between topical nystatin prophylaxis (p= 0.99), length of NICU stay (p= 0.99), time of glucocorticoid exposure (p= 0.99) and candidemia. CONCLUSION: Topical prophylaxis with nystatin and adequate source control proved to be effective in preventing invasive candidiasis in patients admitted to the NICU.

Ceftazidime/avibactam-resistant meropenem-susceptible KPC-producing Klebsiella pneumoniae: Analysis of cases and evaluation of in vitro activity of fosfomycin-containing combinations.

OBJECTIVES: Little is known regarding outcomes and optimal therapeutic regimens of infections caused by Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae (KPC-Kp) resistant to ceftazidime/avibactam (CZA) and susceptible to meropenem (MEM). Although susceptible to MEM in vitro, the possibility of developing MEM resistance overtime is a concern. We describe the clinical characteristics of patients with colonization/infection due to KPC variants with a focus on the in vitro activity of fosfomycin (FOS)-containing combinations. METHODS: Patients with colonization/infection due to a KPC variant were included. Fosfomycin susceptibility was performed by agar dilution method. Synergistic activity of FOS-based combinations was evaluated by gradient strip-agar diffusion method. The emergence of in vitro MEM resistance was also tested. RESULTS: Eleven patients were included: eight with infection [four with ventilator-associated pneumonia and four with bloodstream infections] and three with colonization. Previous therapy with CZA was administered to all patients (with a mean cumulative duration of 23 days). All subjects with infection received meropenem, in monotherapy (n = 4) or with amikacin (n = 2) or fosfomycin (n = 2), and achieved clinical cure. A new CZA-susceptible and MEM-resistant KPC-Kp strain was subsequently isolated in three patients (27.3%). Meropenem/vaborbactam (MVB) showed high in vitro activity, while FOS+MEM combination was synergistic in 40% of cases. In vitro resistance to MEM was observed with maintenance of CZA resistance. CONCLUSIONS: Detection of KPC variants may occur within the same patient, especially if CZA has been previously administered. Although clinical success has been obtained with carbapenems, the emergence of MEM resistance is a concern. Fosfomycin plus meropenem is synergistic and may be a valuable combination option for KPC variants, while MVB may be considered in monotherapy. The detection of KPC variants in an endemic setting for KPC-Kp represents a worryingly emerging condition. The optimal therapeutic approach is still unknown and the development of meropenem resistance is of concern, which may lead to therapeutic failure in clinical practice. In these cases, the addition of fosfomycin to meropenem, or a more potent antibiotic, such as meropenem/vaborbactam, may be valuable therapeutic options.

Changing Italian nosocomial-community trends and heteroresistance in Staphylococcus aureus from bacteremia and endocarditis.

Bloodstream infections due to Staphylococcus aureus (BSI) are serious infections both in hospitals and in the community, possibly leading to infective endocarditis (IE). The use of glycopeptides has been recently challenged by various forms of low-level resistance. This study evaluated the distribution of MSSA and MRSA isolates from BSI and IE in 4 Italian hospitals, their antibiotic susceptibility--focusing on the emergence of hVISA--and genotypic relationships. Our results demonstrate that the epidemiology of MRSA is changing versus different STs possessing features between community-acquired (CA)- and hospital-acquired (HA)-MRSA groups; furthermore, different MSSA isolated from BSI and IE were found, with the same backgrounds of the Italian CA-MRSA. The hVISA phenotype was very frequent (19.5%) and occurred more frequently in isolates from IE and in both the MSSA and MRSA strains. As expected, hVISA were detected in MRSA with vancomycin minimum inhibitory concentrations (MICs) of 1-2 mg/l, frequently associated with the major SCCmec I and II nosocomial clones; this phenotype was also detected in some MSSA strains. The few cases of MR-hVISA infections evaluated in our study demonstrated that 5 out of 9 patients (55%) receiving a glycopeptide, died. Future studies are required to validate these findings in terms of clinical impact.

Laboratory confirmed bloodstream infection aetiology in an intensive care unit: eight years study.

To evaluate laboratory confirmed bloodstream infection (LC-BSI) aetiology we carried out a prospective study in the general 13 bed ICU of the teaching hospital Policlinico Umberto I in Rome. According to CDC case definitions for LC-BSI, all patients admitted >48h between 2000-2007 to ICU were included. Risk factors (i.e. age, sex, SAPS II), invasive procedures (i.e. endotracheal intubation, vascular and urinary catheterisation), microbiological isolates and their antibiotic susceptibility were screened. Overall 1741 patients (64.8% males, 35.2% females) were included, mean age was 58.1 +/- 19.8, SAPS II score 45.1 +/- 17 and ICU stay 14.0 +/- 21.1 days. Finally, 167 (9.6%) patients developed 203 (11.7%) ICU-acquired LC-BSI and sources of infection were CVC (39.8%), unknown (39.3%), respiratory tract (12.4%), surgical wound (6.5%) and urinary tract (2.0%). Between 2000 and 2007 the incidence of LC-BSI/1000 patient days (14.8 per thousands vs. 7.8 per thousands: p<0.05) and LC-BSI/1000 CVC days (20.7 per thousands vs. 11.4 per thousands; p<0.05) decreased. The onset of infection followed ICU admission by 19.5 +/- 17.7 (mean) and 13 days (median). Crude mortality was 34.8%, and mortality associated with LC-BSI showed a RR 1.61; 95%CI 1.37 - 1.89; p<0.01. The most common pathogens were coagulase negative staphylococci (CNS) (26.2%), methicillin-resistant Staphylococcus aureus (MRSA) (14.9%), Pseudomonas aeruginosa (13.5%), enterococci (9.3%) and Acinetobacter bawnumannii (7.5%). Onset time (days) between ICU admission and LC-BSI was higher (p<0.01) among Gram-negative (22.9 +/- 18.4) compared to Gram-positive (16.6 +/- 15.9), fungi (23.8 +/- 25.3). High early death (<7 days after BSI diagnosis) was associated to A. baumannii (37.5%), Candida spp. (30.0%) and S. aureus (29.7%). Staphylococci presented a very high methicillin resistance (>85%). P. aeruginosa and A. baumannii showed respectively 25% and 68.7% multidrug-resistance. Over 1/3 of Eneterobacteriaceae isolates were extended spectrum beta-lactamase (ESBL), but non resulted resistant to carbapenems. Surveillance showed a high incidence of LC-BSI associated to invasive procedures and the presence of multiresistant bacteria.

Effect of ceftazidime/avibactam plus fosfomycin combination on 30†day mortality in patients with bloodstream infections caused by KPC-producing Klebsiella pneumoniae: results from a multicentre retrospective study.

Introduction: The primary outcome of the study was to evaluate the effect on 30 day mortality of the combination ceftazidime/avibactam + fosfomycin in the treatment of bloodstream infections (BSIs) caused by KPC-producing Klebsiella pneumoniae (KPC-Kp). Materials and methods: From October 2018 to March 2021, a retrospective, two-centre study was performed on patients with KPC-Kp BSI hospitalized at Sapienza University (Rome) and ISMETT-IRCCS (Palermo) and treated with ceftazidime/avibactam-containing regimens. A matched cohort (1:1) analysis was performed. Cases were patients receiving ceftazidime/avibactam + fosfomycin and controls were patients receiving ceftazidime/avibactam alone or in combination with in vitro non-active drugs different from fosfomycin (ceftazidime/avibactam ±â€Šother). Patients were matched for age, Charlson comorbidity index, ward of isolation (ICU or non-ICU), source of infection and severity of BSI, expressed as INCREMENT carbapenemase-producing Enterobacteriaceae (CPE) score. Results: Overall, 221 patients were included in the study. Following the 1:1 match, 122 subjects were retrieved: 61 cases (ceftazidime/avibactam + fosfomycin) and 61 controls (ceftazidime/avibactam ±â€Šother). No difference in overall mortality emerged between cases and controls, whereas controls had more non-BSI KPC-Kp infections and a higher number of deaths attributable to secondary infections. Almost half of ceftazidime/avibactam + fosfomycin patients were prescribed fosfomycin without MIC fosfomycin availability. No difference in the outcome emerged after stratification for fosfomycin susceptibility availability and dosage. SARS-CoV-2 infection and ICS ≥ 8 independently predicted 30 day mortality, whereas an appropriate definitive therapy was protective. Conclusions: Our data show that fosfomycin was used in the treatment of KPC-Kp BSI independently from having its susceptibility testing available. Although no difference was found in 30 day overall mortality, ceftazidime/avibactam + fosfomycin was associated with a lower rate of subsequent KPC-Kp infections and secondary infections than other ceftazidime/avibactam-based regimens.

Determinants of prolonged viral RNA shedding in hospitalized patients with SARS-CoV-2 infection.

OBJECTIVE: To evaluate determinants of prolonged viral RNA shedding in hospitalized patients with SARS-CoV-2 infection. MATERIALS AND METHODS: Hospitalized patients with SARS-CoV-2 positive nasopharyngeal RT-PCR were included in a single-center, retrospective study. Patients were divided in 2 groups according to the timing of viral clearance [≤14 days, "early clearance (EC)" and >14 days, "late clearance (LC)"]. RESULTS: 179 patients were included in the study (101 EC, 78 LC), with median age 62 years. Median time of viral shedding was 14 days (EC/LC 10 and 19 days, respectively, P < 0.0001). Univariate analyses showed that age, male gender, receiving corticosteroids, receiving tocilizumab, ICU admission, low albumin and NLR ratio were associated with late viral clearance. In the multivariable analysis, older age (P = 0.016), albumin level (P = 0.048), corticosteroids (P = 0.021), and tocilizumab (P = 0.015) were significantly associated with late viral clearance. CONCLUSIONS: Age, albumin, tocilizumab and corticosteroid treatment were independently associated with a prolonged SARS-CoV-2 RNA shedding.

A seven-year prospective study on spondylodiscitis: epidemiological and microbiological features.

BACKGROUND: The aim of this paper was to enlarge the available knowledge on clinical and etiological aspects of patients affected by spondylodiscitis. PATIENTS AND METHODS: All patients with spondylodiscitis admitted between January 2001 and December 2007 at the 1,300-bed University Hospital "Policlinico Umberto I" of Rome, Italy, were followed. Demographic characteristics, underlying diseases, invasive procedures, imaging studies, isolated microorganisms, treatment, complications, and outcome were recorded. RESULTS: Eighty-one patients of mean age 57.7 +/- 14.7 years with lumbosacral (72.8%), thoracic (14.8%), and cervical tract (12.3%) site of infection were included, of which 38 developed community-acquired (CA) spondylodiscitis and 43 developed hospital-acquired (HA) spondylodiscitis. Underlying disease was present in 49.4% of patients. HA spondylodiscitis was diagnosed earlier (46.8 +/- 49.7 days) than CA spondylodiscitis (65.0 +/- 55.4 days) (P < 0.05). The most frequently isolated microorganisms were Staphylococcus aureus (28 strains, 43.1%), coagulase-negative staphylococci (CNS) (eight strains, 12.3%), Pseudomonas aeruginosa (eight strains, 12.3%), and three methicillin-resistant S. aureus (MRSA) strains were isolated in CA spondylodiscitis. Fungi and yeasts, isolated in six patients, represented 9.2% of all strains but 17.6% when considering only HA spondylodiscitis. Over 85% of patients were managed by conservative treatment alone, and the treatment time depended on clinical and laboratory evidence. Poor outcome was recorded in 12 (14.8%) patients, and was associated with neurological deficit symptoms (relative risk [RR] 2.87; 95% confidence interval [CI] 1.02-8.07; P < 0.05) and the time between diagnosis and the onset of symptoms > or = 60 days (RR 2.65; 95% CI 0.92-7.59; P < 0.05). CONCLUSIONS: Infectious spondylodiscitis affects most frequently the elderly population, who are more exposed to healthcare contacts. Consequently, the infection etiology includes a growing proportion of multi-resistant bacteria and fungi.

What is MRSA?

For decades methicillin-resistant Staphylococcus aureus (MRSA) has been considered the prototype of multi-resistant nosocomial pathogens, causing infections in high-risk patients. Changes in the healthcare system, coupled with the evolution of this versatile microorganism, have transformed MRSA into a cause of community-onset infections, in both patients who have contact with the healthcare system and patients without such a risk factor. New lineages of MRSA, defined as community acquired (CA)-MRSA, have emerged that have a propensity to cause infections in young individuals without risk factors. CA-MRSA primarily causes skin infections and, rarely, necrotising pneumonia. In the USA, these strains belong to a single widespread clone, designated USA300, while in Europe they belong to a variety of clones. Most strains carry genes for the Panton-Valentine leukocidin, whose role in diseases is under debate. In subjects living in the community who have contact with the healthcare system, MRSA strains of the nosocomial type are a frequent cause of infection and of pneumonia in particular. The detection of a large MRSA reservoir in pigs and the finding that professionally exposed individuals are colonised, has further shown that it is necessary to closely follow the epidemiology of MRSA if we want to combat it effectively.

Italian guidelines for the diagnosis and infectious disease management of osteomyelitis and prosthetic joint infections in adults.

Bone and joint infections are recognized as difficult-to-treat infections that result in significant morbidity and mortality among patients and increased healthcare costs. This article presents the recommendations for the diagnosis and management of osteomyelitis and prosthetic joint infections in adults developed by Bone and Joint Infections Committee for the Italian Society of Infectious and Tropical Diseases. It contains data published through to November 2007. An evidence-based scoring system that is used by the Infectious Diseases Society of America was applied to treatment recommendations.