Non-cholera Vibrio spp. invasive infections in the summer following May 2023 flood disaster in Romagna, Italy: a case series.

Non-cholera Vibrio spp. includes ubiquitous organisms living in aquatic environments. Their occurrence is associated with global warming and meteorological disasters. In May 2023 the Romagna region, Italy, was affected by severe floods. In the following 15 weeks we observed 5 patients with invasive infections caused by V. vulnificus (3/5) and V. harveyi (2/5). All patients (median age 77 years) had medical comorbidities and shared exposure to seawater. Two patients needed surgery; 2 died. In conclusion, we observed an increased burden of Vibrio spp. invasive infections after May 2023 floods, affecting old patients with predisposing medical conditions.

Intermediate dose enoxaparin in hospitalized patients with moderate-severe COVID-19: a pilot phase II single-arm study, INHIXACOVID19.

BACKGROUND: Randomized clinical trials in non-critically ill COVID-19 patients showed that therapeutic-dose heparin increased survival with reduced organ support as compared with usual-care thromboprophylaxis, albeit with increased bleeding risk. The purpose of the study is to assess the safety of intermediate dose enoxaparin in hospitalized patients with moderate to severe COVID-19. METHODS: A phase II single-arm interventional prospective study including patients receiving intermediate dose enoxaparin once daily according to body weight: 60 mg for 45-60 kg, 80 mg for 61-100 kg or 100 mg for > 100 kg for 14 days, with dose adjustment according to anti-factor Xa activity (target range: 0.4-0.6 UI/ml); an observational cohort (OC) included patients receiving enoxaparin 40 mg day for comparison. Follow-up was 90 days. Primary outcome was major bleeding within 30 and 90 days after treatment onset. Secondary outcome was the composite of all-cause 30 and 90-day mortality rates, disease severity at the end of treatment, intensive care unit (ICU) admission and length of ICU stay, length of hospitalization. All outcomes were adjudicated by an independent committee and analyzed before and after propensity score matching (PSm). RESULTS: Major bleeding was similar in IC (1/98 1.02%) and in the OC (none), with only one event observed in a patient receiving concomitantly anti-platelet therapy. The composite outcome was observed in 53/98 patients (54%) in the IC and 132/203 (65%) patients in the OC (p = 0.07) before PSm, while it was observed in 50/90 patients (55.6%) in the IC and in 56/90 patients (62.2%) in the OC after PSm (p = 0.45). Length of hospitalization was lower in the IC than in OC [median 13 (IQR 8-16) vs 14 (11-21) days, p = 0.001], however it lost statistical significance after PSm (p = 0.08). At 30 days, two patients had venous thrombosis and two pulmonary embolism in the OC. Time to first negative RT-PCR were similar in the two groups. CONCLUSIONS: Weight adjusted intermediate dose heparin with anti-FXa monitoring is safe with potential positive impact on clinical course in COVID-19 non-critically ill patients. TRIAL REGISTRATION: The study INHIXACOVID19 was registred on ClinicalTrials.gov with the trial registration number (TRN) NCT04427098 on 11/06/2020.

The impact of carbapenemase-producing Enterobacteriaceae colonization on infection risk after liver transplantation: a prospective observational cohort study.

OBJECTIVE: To investigate the impact of colonization with carbapenemase-producing Enterobacteriaceae (CPE) on the CPE infection risk after liver transplantation (LT). METHODS: Prospective cohort study of all adult patients undergoing LT at our centre over an 8-year period (2010-2017). Individuals were screened for CPE colonization by rectal swabs at inclusion onto the waiting list, immediately before LT and weekly after LT until hospital discharge. Asymptomatic carriers did not receive decolonization, anti-CPE prophylaxis or pre-emptive antibiotic therapy. Participants were followed up for 1 year after LT. RESULTS: We analysed 553 individuals who underwent a first LT, 38 were colonized with CPE at LT and 104 acquired colonization after LT. CPE colonization rates at LT and acquired after LT increased significantly over the study period: incidence rate ratios (IRR) 1.21 (95% CI 1.05-1.39) and 1.17 (95% CI 1.07-1.27), respectively. Overall, 57 patients developed CPE infection within a median of 31 (interquartile range 11-115) days after LT, with an incidence of 3.05 cases per 10 000 LT-recipient-days and a non-significant increase over the study period (IRR 1.11, 95% CI 0.98-1.26). In multivariable analysis, CPE colonization at LT (hazard ratio (HR) 18.50, 95% CI 6.76-50.54) and CPE colonization acquired after LT (HR 16.89, 95% CI 6.95-41.00) were the strongest risk factors for CPE infection, along with combined transplant (HR 2.60, 95% CI 1.20-5.59), higher Model for End-Stage Liver Disease at the time of LT (HR 1.03, 95% CI 1.00-1.07), prolonged mechanical ventilation (HR 2.63, 95% CI 1.48-4.67), re-intervention (HR 2.16, 95% CI 1.21-3.84) and rejection (HR 2.81, 95% CI 1.52-5.21). CONCLUSIONS: CPE colonization at LT or acquired after LT were the strongest predictors of CPE infection. Prevention strategies focused on LT candidates and recipients colonized with CPE should be investigated.

Superficial swab versus deep-tissue biopsy for the microbiological diagnosis of local infection in advanced-stage pressure ulcers of spinal-cord-injured patients: a prospective study.

OBJECTIVE: To assess the predictive value of superficial ulcer swab culture to make a microbiological diagnosis of deep wound infections in spinal cord injury (SCI) patients with advanced-stage pressure ulcers. METHODS: From July 2011 to February 2014, we performed a prospective, single-centre study on adult SCI patients undergoing scheduled surgical debridement and reconstruction for advanced-stage pressure ulcers, at Montecatone Rehabilitation Institute, a 150-bed hospital dedicated to SCI care. Three superficial ulcer swabs were preoperatively collected using the Levine technique, then sent for culture. In surgery, multiple bone and soft-tissue specimens were taken and sent for culture and histological examination. No antibiotics were administered before surgery. The results of swabs and intraoperative specimens were compared. RESULTS: In all, 116 patients were included, median age 49 years; a majority were males with post-traumatic paraplegia. According to intraoperative specimen cultures, the most common micro-organisms were Staphylococcus aureus, Proteus mirabilis, and Pseudomonas aeruginosa, found in 31, 27, and 16 cases, respectively. Concordance between superficial swabs and intraoperative specimen culture was found in only in 25 out of 116 cases (22%). The main reason for non-concordance was the yielding of different micro-organisms (41 out of 116); false negatives (swab negative/intraoperative positive) accounted for 31 out of 116 and false positives (swab positive/intraoperative negative) for 19 out of 116. When compared with intraoperative specimens, sensitivity and specificity of the swab culture were 80% and 54%, respectively. CONCLUSIONS: Our results confirm that in patients with advanced-stage pressure ulcers, the cultures of a superficial ulcer swab are not useful in either the diagnosis of a superinfection or the prediction of the role of involved micro-organisms.

Impact of preoperative infection on outcome after liver transplantation.

BACKGROUND: Bacterial infection in patients with liver failure can lead to a dramatic clinical deterioration. The indications for liver transplantation and outcome in these patients is still controversial. METHODS: All adult patients who underwent liver transplantation between 1 January 2010 and 31 December 2015 were selected from an institutional database. Characteristics of the donors and recipients, and clinical, biochemical and surgical parameters were retrieved from the database. Post-transplant survival rates and complications, including grade III-IV complications according to the Dindo-Clavien classification, were compared between patients with an infection 1 month before transplantation and patients without an infection. RESULTS: Eighty-four patients with an infection had statistically significant higher Model for End-stage Liver Disease (MELD), D-MELD and Balance of Risk (BAR) scores and a higher rate of acute-on-chronic liver failure compared with findings in 343 patients with no infection. The rate of infection after liver transplantation was higher in patients who had an infection before the operation: 48 per cent versus 30·6 per cent in those with no infection before transplantation (P = 0·003). The percentage of patients with a postoperative complication (42 versus 40·5 per cent respectively; P = 0·849) and the 90-day mortality rate (8 versus 6·4 per cent; P = 0·531) was no different between the groups. Multivariable analysis showed that a BAR score greater than 18 and acute-on-chronic liver failure were independent predictors of 90-day mortality. CONCLUSION: Bacterial infection 1 month before liver transplantation is related to a higher rate of infection after transplantation, but does not lead to a worse outcome.

Antifungal prophylaxis in liver transplant recipients: one size does not fit all.

BACKGROUND: Targeted antifungal prophylaxis against Candida species or against Candida species and Aspergillus species, according to individual patient risk factors (RFs), is recommended by experts. However, recent studies have reported fluconazole is as effective as broader spectrum antifungals for preventing invasive fungal infection (IFI) after liver transplantation (LT). METHODS: We performed a retrospective cohort study of all adult patients who underwent LT at our 1420-bed tertiary teaching hospital, from June 2010 to December 2014, to assess the rate and etiology of IFI within 100 days after LT, to investigate the compliance with targeted prophylaxis, and to analyze risk factors for developing IFI. RESULTS: In total, 303 patients underwent LT. Patients were classified as having low (no RFs), intermediate (1 RF for invasive candidiasis [IC]), and high risk (1 RF for invasive aspergillosis [IA] or ≥2 RFs for IC) for IFI in 20%, 30%, and 50% of cases, respectively. A total of 139 patients received antifungal prophylaxis: 98 with a mold-active drug and 41 with fluconazole. Overall adherence to targeted prophylaxis was 53%. Nineteen patients (6.3%) developed IFI: 7 IC and 12 IA. Multivariate Cox regression analysis, adjusted for median model for end-stage liver disease score at LT, stratification risk group, and adherence to targeted prophylaxis, showed that graft dysfunction, renal replacement therapy, and prophylaxis with fluconazole were independent risk factors for IFI. Seven of the 9 patients who received fluconazole prophylaxis and developed IFI were classified as having high risk for IFI, and 6 developed IA. CONCLUSION: Recommended stratification is accurate for predicting patients at very high risk for IFI, who should receive prophylaxis with a mold-active drug.

Current and future trends in antibiotic therapy of acute bacterial skin and skin-structure infections.

In 2013 the US Food and Drug Administration (FDA) issued recommendations and guidance on developing drugs for treatment of skin infection using a new definition of acute bacterial skin and skin-structure infection (ABSSSI). The new classification includes cellulitis, erysipelas, major skin abscesses and wound infection with a considerable extension of skin involvement, clearly referring to a severe subset of skin infections. The main goal of the FDA was to better identify specific infections where the advantages of a new antibiotic could be precisely estimated through quantifiable parameters, such as improvement of the lesion size and of systemic signs of infection. Before the spread and diffusion of methicillin-resistant Staphylococcus aureus (MRSA) in skin infections, antibiotic therapy was relatively straightforward. Using an empiric approach, a ß-lactam was the preferred therapy and cultures from patients were rarely obtained. With the emergence of MRSA in the community setting, initial ABSSSI management has been changed and readdressed. Dalbavancin, oritavancin and tedizolid are new drugs, approved or in development for ABSSSI treatment, that also proved to be efficient against MRSA. Dalbavancin and oritavancin have a long half-life and can be dosed less frequently. This in turn makes it possible to treat patients with ABSSSI in an outpatient setting, avoiding hospitalization or potentially allowing earlier discharge, without compromising efficacy. In conclusion, characteristics of long-acting antibiotics could represent an opportunity for the management of ABSSSI and could profoundly modify the management of these infections by reducing or in some cases eliminating both costs and risks of hospitalization.

Risk factors for infection with carbapenem-resistant Klebsiella pneumoniae after liver transplantation: the importance of pre- and posttransplant colonization.

Improved understanding of risk factors associated with carbapenem-resistant-Klebsiella pneumoniae (CR-KP) infection after liver transplantation (LT) can aid development of effective preventive strategies. We performed a prospective cohort study of all adult patients undergoing LT at our hospital during 30-month period to define risk factors associated with CR-KP infection. All patients were screened for CR-KP carriage by rectal swabs before and after LT. No therapy was administered to decolonize or treat asymptomatic CR-KP carriers. All patients were monitored up to 180 days after LT. Of 237 transplant patients screened, 41 were identified as CR-KP carriers (11 at LT, 30 after LT), and 20 developed CR-KP infection (18 bloodstream-infection, 2 pneumonia) a median of 41.5 days after LT. CR-KP infection rates among patients non-colonized, colonized at LT, and colonized after LT were 2%, 18.2% and 46.7% (p < 0.001). Independent risk factors for CR-KP infection identified by multivariate analysis, included: renal-replacement-therapy; mechanical ventilation > 48 h; HCV recurrence, and colonization at any time with CR-KP. Based on these four variables, we developed a risk score that effectively discriminated patients at low versus higher risk for CR-KP infection (AUC 0.93, 95% CI 0.86-1.00, p < 0.001). Our results may help to design preventive strategies for LT recipients in CR-KP endemic areas.

Impact of a hospital-wide multifaceted programme for reducing carbapenem-resistant Enterobacteriaceae infections in a large teaching hospital in northern Italy.

We performed a quasi-experimental study of a multifaceted infection control programme for reducing carbapenem-resistant Enterobacteriaceae (CRE) transmission and bloodstream infections (BSIs) in a 1420-bed university-affiliated teaching hospital during 2010-2014, with 30 months of follow-up. The programme consisted of the following: (a) rectal swab cultures were performed in all patients admitted to high-risk units (intensive-care units, transplantation, and haematology) to screen for CRE carriage, or for any room-mates of CRE-positive patients in other units; (b) cohorting of carriers, managed with strict contact precautions; (c) intensification of education, cleaning and hand-washing programmes; and (d) promotion of an antibiotic stewardship programme carbapenem-sparing regimen. The 30-month incidence rates of CRE-positive rectal cultures and BSIs were analysed with Poisson regression. Following the intervention, the incidence rate of CRE BSI (risk reduction 0.96, 95% CI 0.92-0.99, p 0.03) and CRE colonization (risk reduction 0.96, 95% CI 0.95-0.97, p <0.0001) significantly decreased over a period of 30 months. After accounting for changes in monthly census and percentage of externally acquired cases (positive at ≤72 h), the average institutional monthly rate of compliance with CRE screening procedures was the only independent variable associated with a declining monthly incidence of CRE colonization (p 0.002). The monthly incidence of CRE carriage was predictive of BSI (p 0.01). Targeted screening and cohorting of CRE carriers and infections, combined with cleaning, education, and antimicrobial stewardship measures, significantly decreased the institutional incidence of CRE BSI and colonization, despite endemically high CRE carriage rates in the region.

An Italian consensus for invasive candidiasis management (ITALIC).

INTRODUCTION: Invasive candidiasis (IC) has primarily been studied in intensive care unit (ICU) patients, although, in reality, a vast majority of these infections occur outside of the ICU. The recent publication of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guidelines also deal with the non-ICU population, but many uncertainties remain on the management of IC, particularly in non-critically ill patients. METHODS: The Italian Society of Antimicrobial Therapy, Società Italiana di Terapia Antimicrobica (SITA), produced practical, hospital-wide recommendations on the management of Candida infection in non-immunocompromised patients in the hospital ward. RESULTS AND DISCUSSION: Our focus is on patient stratification in terms of risk factors for IC and of clinical severity, emphasising a high index of suspicion to ensure early diagnosis, early treatment and de-escalation when a patient is clinically stable, in order to optimise resource allocation.

Spinal infection multidisciplinary management project (SIMP): from diagnosis to treatment guideline.

Spine infections require a multidisciplinary approach to be treated and solved. A guide line to drive physicians in the deep complexity of such a disease is extremely helpful. SIMP suggests a flow-chart built up on clear concepts such as right and well managed antibiotic therapy, sound stability of the spine, correct and smart use of the standard and functional imaging techniques, such as f18 FDG PET/CT. In 16 months a total of 41 patients have been treated for spondylodiscitis, discitis and vertebral osteomyelitis by our team of physicians and 25 patients have been enrolled in a prospective study whose target is the assessment of the SIMP flow-chart and of every single aspect that characterize it.

Bile duct injuries during laparoscopic cholecystectomy: a 1994-2001 audit on 13,718 operations in the area of Rome.

BACKGROUND: Bile duct injuries (BDIs) during laparoscopic cholecystectomy (LC) still are reported with greater frequency than during open cholecystectomy (OC). METHODS: In 1999, a retrospective study evaluating the incidence of BDIs during LC in the area of Rome from 1994 to 1998 (group A) was performed. In addition, a prospective audit was started, ending in December 2001 (group B). RESULTS: In group A, 6,419 LCs were performed (222 were converted to OC; 3.4%). In group B, 7,299 LCs were performed (225 were converted to OC; 3.1%). Seventeen BDIs (0.26%) occurred in group A and 16 (0.22%) in group B. Overall, mortality and major morbidity rates were 12.1% and 30.3%, respectively, without significant differences between the two groups. CONCLUSIONS: The incidence and clinical relevance of BDIs during LC in the area of Rome appeared to be stable over the past 8 years and were not influenced by the use of a prospective audit, as compared with a retrospective survey.

In vitro susceptibility testing of Geotrichum capitatum: comparison of the E-test, disk diffusion, and Sensititre colorimetric methods with the NCCLS M27-A2 broth microdilution reference method.

The in vitro activities of amphotericin B, flucytosine, fluconazole, itraconazole, and voriconazole against 23 isolates of Geotrichum capitatum were determined by the National Committee for Clinical Laboratory Standards (NCCLS) M27-A2 microdilution method and the Sensititre and agar diffusion methods. Amphotericin B and voriconazole appeared to be the more active drugs. Sensititre showed the highest rates of agreement with the NCCLS M27-A2 method.

Antibiotic lock-technique for the treatment of catheter-related bloodstream infections.

The management of central venous catheter-related bloodstream infections (CRBSI), though still debated, requires the removal of the line in most cases: we investigated the efficacy of an alternative approach, based on higher concentrations of antibiotics locked within the catheter lumen, in an open, pilot study aimed at preserving the line in place and at eradicating the infection. Thirty consecutive patients carrying a central line over 10 days and who fulfilled criteria for ascertained diagnosis of bacterial CRBSI, had the catheter "locked" with antimicrobials therein; all patients also received systemic antibiotic therapy within the first 48 hours. Subsequently, 15 patients underwent locks alone, and 15 locks plus systemic therapy. Twenty-eight out of 30 (93.3%) patients retained the catheter in place, appearing to be cleared of infection and no treatment-related untoward events were observed. Locks should be considered as effective as line removal in the management of bacterial CRBSI in unselected patients, and could thus provide advantages in terms of resource sparing and lowered antibiotic pressure in the hospital setting.

Sequential regimen for early post-surgical infective endocarditis due to methicillin-resistant Staphylococcus aureus (MRSA), unresponsive to standard antibiotic therapy: a case report.

We describe a patient with early post-surgical infective endocarditis due to methicillin-resistant Staphylococcus aureus, who was unsuitable for surgical reintervention and who failed standard antistaphylococcal therapy, but was successfully cured with a sequential regimen including quinupristin/dalfopristin and linezolid.

Histone modification in early and late Drosophila embryos.

Levels of histone acetylation and phosphorylation have been contrasted in two developmental states of Drosophila melanogaster. The 0-2 h nuclei of the syncitial blastula are characterized by rapid mitoses and DNA replication, but there is very little transcription. In the 18 h embryo there is considerable transcription and the mitotic rate is much slower. It has been found that (1) histone H1 from 2h nuclei is not highly phosphorylated. This observation is not in accord with the view that H1 hyperphosphorylation is essential to mitosis, but is compatible with the hypothesis that H1 phosphorylation in Drosophila species is related to heterochromatization. (2) Histone H4 from 2 h embryos shows high levels of the diacetyl form (H4-Ac2), which is principally outside the nucleus. This accords with the hypothesis that H4-Ac2 is the form in which H4 is deposited on to newly replicated DNA and shows that H4 acetylation is linked not only to transcription. (3) Histone H3 acetylation is similar in 2h and in 18h embryos. As with H4, this acetylation probably correlates with chromatin assembly and is not transcription-related. (4) Histone H2B carries no modification in 2h or in 18h embryos, and H2A shows a single modification in 2h embryos and two in 18 h embryos. H2B modification is thus not essential either in mitosis or replication, whereas H2A modification is important in one or both processes. (5) The nucleosomal protein D2 is equally present in 2h and 18 h embryos.