A simplified regimen of targeted antifungal prophylaxis in liver transplant recipients: A single-center experience.

BACKGROUND: Invasive fungal infection (IFI) is a severe complication of liver transplantation burdened by high mortality. Guidelines recommend targeted rather than universal antifungal prophylaxis based on tiers of risk. METHODS: We aimed to evaluate IFI incidence, risk factors, and outcome after implementation of a simplified two-tiered targeted prophylaxis regimen based on a single broad-spectrum antifungal drug (amphotericin B). Patients presenting 1 or more risk factors according to literature were administered prophylaxis. Prospectively collected data on all adult patients transplanted in Turin from January 2011 to December 2015 were reviewed. RESULTS: Patients re-transplanted before postoperative day 7 were considered once, yielding a study cohort of 581 cases. Prophylaxis was administered to 299 (51.4%) patients; adherence to protocol was 94.1%. Sixteen patients developed 18 IFIs for an overall rate of 2.8%. All IFI cases were in targeted prophylaxis group; none of the non-prophylaxis group developed IFI. Most cases (81.3%) presented within 30 days after transplantation during prophylaxis; predominant pathogens were molds (94.4%). Only 1 case of candidemia was observed. One-year mortality in IFI patients was 33.3% vs 6.4% in patients without IFI (P = .001); IFI attributable mortality was 6.3%. At multivariate analysis, significant risk factors for IFI were renal replacement therapy (OR = 8.1) and re-operation (OR = 5.2). CONCLUSIONS: The implementation of a simplified targeted prophylaxis regimen appeared to be safe and applicable and was associated with low IFI incidence and mortality. Association of IFI with re-operation and renal replacement therapy calls for further studies to identify optimal prophylaxis in this subset of patients.

Previous bloodstream infections due to other pathogens as predictors of carbapenem-resistant Klebsiella pneumoniae bacteraemia in colonized patients: results from a retrospective multicentre study.

INTRODUCTION: the purpose of this retrospective multicenter study was to assess whether the risk of developing bloodstream infections (BSI) due to carbapenem-resistant Klebsiella pneumoniae (CRKP) in colonized patients is influenced by the occurrence of BSI due to other pathogens. METHODS: from January 2012 to March 2014, all patients with at least one rectal swab positive for CRKP and at least 30 days of previous hospital stay were included in the study. The primary outcome measure was CRKP BSI, defined as a time-to-event endpoint. The role of potential predictors was evaluated through univariable and multivariable Cox regression analyses, considering previous BSI as a time-dependent variable. RESULTS: during the study period, 353 patients met the inclusion criteria. Thirty-seven developed a CRKP BSI (11%). A higher incidence of CRKP BSI was observed in presence rather than in absence of previous BSI. In the final multivariable model of risk factors for CRKP BSI, multisite colonization (hazard ratio [HR] 13.73, 95% confidence intervals [CI] 3.29-57.32, p < 0.001), ICU stay (HR 3.14, 95% CI 1.19-8.31, p = 0.021), and previous BSI (p = 0.026, with the overall effect being mainly due to Enterococcus spp. BSI vs absence of BSI, HR 6.62, 95% CI 2.11-20.79) were associated with the development of CRKP BSI, while an inverse association was observed for age (HR 0.98, 95% CI 0.95-1.00, p = 0.027). CONCLUSIONS: previous BSI due to other pathogens were associated with an increased risk of CRKP BSI that was independent of other factors in colonized patients with prolonged hospital exposure.

Intrathecal/intraventricular colistin in external ventricular device-related infections by multi-drug resistant Gram negative bacteria: case reports and review.

We report three cases of external ventricular derivation infections caused by multidrug-resistant Gram-negative rods and treated successfully with intraventricular colistin. The intrathecal or intraventricular use of colistin have been reported in more than 100 cases without any consensus on dosage, duration and type (monotherapy or combination therapy) of treatment. Based on our comprehensive review of the relevant literature relating to both clinical and pharmacokinetic data, we conclude that the intrathecal/intraventricular administration of colistin is a safe and effective option to treat central nervous system infections caused by multidrug-resistant Gram-negative bacteria.

Impact of COVID-19 on healthcare-associated infections and antimicrobial use in Italy, 2022.

BACKGROUND: It is unknown whether COVID-19 patients are at higher risk due to demographic and clinical characteristics associated with higher COVID-19 infection risk and severity of infection, or due to the disease and its management. AIM: To assess the impact of COVID-19 on healthcare-associated infection (HAI) transmission and antimicrobial use (AMU) prevalence during the later stages of the pandemic. METHODS: A point-prevalence survey (PPS) was conducted among 325 acute care hospitals of 19 out of 21 Regions of Italy, during November 2022. Non-COVID-19 patients were matched to COVID-19 patients according to age, sex, and severity of underlying conditions. HAI and AMU prevalence were calculated as the percentage of patients with at least one HAI or prescribed at least one antimicrobial over all included patients, respectively. FINDINGS: In total, 60,403 patients were included, 1897 (3.14%) of which were classified as COVID-19 patients. Crude HAI prevalence was significantly higher among COVID-19 patients compared to non-COVID-19 patients (9.54% vs 8.01%; prevalence rate ratio (PRR): 1.19; 95% confidence interval (CI): 1.04-1.38; P < 0.05), and remained higher in the matched sample; however, statistical significance was not maintained (odds ratio (OR): 1.25; 95% CI: 0.99-1.59; P = 0.067). AMU prevalence was significantly higher among COVID-19 patients prior to matching (46.39% vs 41.52%; PRR: 1.21; 95% CI: 1.11-1.32; P < 0.001), and significantly lower after matching (OR: 0.77; 95% CI: 0.66-0.89; P < 0.001). CONCLUSION: COVID-19 patients could be at higher HAI risk due to underlying clinical conditions and the intensity of healthcare needs. Further efforts should be dedicated to antimicrobial stewardship among COVID-19 patients.

The reversed halo sign as the initial radiographic sign of pulmonary zygomycosis.

Zygomycosis is an emerging fungal infection that is associated with high mortality in hematological patients and stem cell transplantation (SCT) recipients. Radiology--computed tomography (CT) imaging in particular--facilitates the detection of lung involvement at an early stage of the infection. The reversed halo sign (RHS) has previously been reported in cryptogenetic organizing pneumonia and, more recently, as a manifestation of pulmonary zygomycosis. Here we describe a case of histologically proven zygomycosis due to Rhizopus microsporus in a SCT recipient. A chest CT scan performed on day +6 due to persistent fever unresponsive to antibiotics revealed the presence of the RHS, i.e., a focal ground-glass opacity mass surrounded by a solid ring of consolidation. The patient was treated with a combination of liposomal amphotericin B, caspofungin, and deferasirox, but subsequently developed a large pneumothorax and died on day +49 due to progressive infection. This case supports earlier observations that RHS may be an early radiological sign of zygomycosis, facilitating an aggressive diagnostic strategy.

Blood stream infections after allogeneic stem cell transplantation: a single-center experience with the use of levofloxacin prophylaxis.

Blood stream infections (BSIs) remain one of the major causes of morbidity and mortality for patients receiving an allogeneic hematopoietic stem cell transplantation (HSCT). In the present study, we evaluated the incidence and characteristics of BSI within 1 year after allogeneic HSCT in 269 consecutive adult patients who received antibacterial prophylaxis with levofloxacin. Cumulative incidence of BSI was 12% (95% confidence interval, 8-16%). Bacteria were responsible for 30 out of the 32 BSI, while fungi were responsible for 2 episodes of BSI. The median onset of BSI was day 8 (range 1-328 days) post transplant, and 66% of BSI occurred before neutrophil recovery. Gram-positive organisms accounted for 60% (n=18) of bacteremia, and gram-negative isolates for 40% (n=12) of the cases. Coagulase-negative staphylococci were the most commonly isolated gram-positive pathogens (53% of the cases), while Escherichia coli was the most commonly isolated gram-negative bacteria (58% of the cases). Candida albicans and Candida guillermondii were isolated from patients with candidemia. Resistance to fluoroquinolones (FQ) was common with 13% of gram-positive isolates being susceptible to FQ, while 50% of the gram-negative rods were susceptible to FQ. Crude mortality and mortality attributable to BSI were both 3% (1 of 32). In conclusion, our data suggest that despite the emergence of antibiotic resistance, FQ prophylaxis may be considered an appealing approach in allogeneic HSCT recipients and is also worth evaluating in randomized studies.

The effect of inappropriate therapy on bacteremia by ESBL-producing bacteria.

OBJECTIVE: To describe the impact of empiric appropriate treatment and the risk factors associated with mortality in patients with bacteremia by E. coli, K. pneumoniae and P. mirabilis producing ESBL. METHODS: Data were reviewed in an 8-year retrospective study, and 128 bacteremias were found: 80 caused by E. coli (62.5%), 28 by K. pneumoniae (21.9%) and 20 by P. mirabilis (18.6%). RESULTS: The initial antibiotic treatment, administered within 72 h after the first positive blood culture, was appropriate with carbapenems or other antimicrobial agents with documented in vitro sensitivity in 53.8 and 16% of patients, respectively. The overall mortality 21 days after diagnosis was 17.2%, and it was 14.9 and 35.2% for patients adequately and inadequately treated, respectively. At univariate analysis the p value for mortality with and without appropriate treatment was 0.05, and significant differences were found only for previous positive blood cultures (p = 0.004) and presence of septic shock at diagnosis (p = 0.006). CONCLUSION: In this case series there was a high rate of initial appropriate empiric treatment, and only a marginal impact on mortality was found with regard to appropriate and inappropriate treatment. This report shows that the knowledge of ESBL-producing characteristics varies widely among the different case series for reasons that still have to be clarified.

Risk factors for invasive aspergillosis in ICU patients with COVID-19: current insights and new key elements.

Invasive pulmonary aspergillosis (IPA) has always been a challenging diagnosis and risk factors an important guide to investigate specific population, especially in Intensive Care Unit. Traditionally recognized risk factors for IPA have been haematological diseases or condition associated with severe immunosuppression, lately completed by chronic conditions (such as obstructive pulmonary disease, liver cirrhosis, chronic kidney disease and diabetes), influenza infection and Intensive Care Unit (ICU) admission. Recently, a new association with SARS-CoV2 infection, named COVID-19-associated pulmonary aspergillosis (CAPA), has been reported worldwide, even if its basic epidemiological characteristics have not been completely established yet. In this narrative review, we aimed to explore the potential risk factors for the development of CAPA and to evaluate whether previous host factors or therapeutic approaches used in the treatment of COVID-19 critically ill patients (such as mechanical ventilation, intensive care management, corticosteroids, broad-spectrum antibiotics, immunomodulatory agents) may impact this new diagnostic category. Reviewing all English-language articles published from December 2019 to December 2020, we identified 21 papers describing risk factors, concerning host comorbidities, ICU management, and COVID-19 therapies. Although limited by the quality of the available literature, data seem to confirm the role of previous host risk factors, especially respiratory diseases. However, the attention is shifting from patients' related risk factors to factors characterizing the hospital and intensive care course, deeply influenced by specific features of COVID treatment itself. Prolonged invasive or non-invasive respiratory support, as well as the impact of corticosteroids and/or immunobiological therapies seem to play a pivotal role. ICU setting related factors, such as environmental factors, isolation conditions, ventilation systems, building renovation works, and temporal spread with respect to pandemic waves, need to be considered. Large, prospective studies based on new risk factors specific for CAPA are warranted to guide surveillance and decision of when and how to treat this particular population.

Carbapenem-resistant Klebsiella pneumoniae in ICU-admitted COVID-19 patients: Keep an eye on the ball.

Here we report on seven intensive care unit (ICU) patients with coronavirus disease 2019 (COVID-19)-related acute respiratory distress syndrome (ARDS) who developed positive rectal swabs and invasive infections due to carbapenemase-producing Klebsiella pneumoniae (CP-Kp). Notwithstanding the infection prevention measures introduced during the COVID-19 pandemic and changes in the hospitalised population, attention to CP-Kp infections must remain high, especially in the critically ill setting.

Balancing evidence and frontline experience in the early phases of the COVID-19 pandemic: current position of the Italian Society of Anti-infective Therapy (SITA) and the Italian Society of Pulmonology (SIP).

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19), which has rapidly become epidemic in Italy and other European countries. The disease spectrum ranges from asymptomatic/mildly symptomatic presentations to acute respiratory failure. At the present time the absolute number of severe cases requiring ventilator support is reaching or even surpassing the intensive care unit bed capacity in the most affected regions and countries. OBJECTIVES: To narratively summarize the available literature on the management of COVID-19 in order to combine current evidence and frontline opinions and to provide balanced answers to pressing clinical questions. SOURCES: Inductive PubMed search for publications relevant to the topic. CONTENT: The available literature and the authors' frontline-based opinion are summarized in brief narrative answers to selected clinical questions, with a conclusive statement provided for each answer. IMPLICATIONS: Many off-label antiviral and anti-inflammatory drugs are currently being administered to patients with COVID-19. Physicians must be aware that, as they are not supported by high-level evidence, these treatments may often be ethically justifiable only in those worsening patients unlikely to improve only with supportive care, and who cannot be enrolled onto randomized clinical trials. Access to well-designed randomized controlled trials should be expanded as much as possible because it is the most secure way to change for the better our approach to COVID-19 patients.

V348I mutation in UL23 gene of human herpesvirus 1 in a case of herpetic hepatitis and haemophagocytic lymphohistiocytosis.

We herein report the case of a young immunocompetent adult patient with a rapidly fatal haemophagocytic lymphohistiocytosis syndrome related to human herpesvirus 1 (HHV-1) infection, with herpetic hepatitis and persistent high-level viraemia despite treatment with acyclovir. Haemophagocytic lymphohistiocytosis was confirmed in the patient's spleen and bone marrow. HHV-1 DNA was extracted from whole blood and liver biopsy and the UL23 gene was sequenced. A V348I natural polymorphism of the TK protein was found in blood and liver specimens. Further studies are needed to investigate the role of this polymorphism in the development of systemic immune dysregulation.

Management of KPC-producing Klebsiella pneumoniae infections.

BACKGROUND: Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae (KPC-KP) has become one of the most important contemporary pathogens, especially in endemic areas. AIMS: To provide practical suggestion for physicians dealing with the management of KPC-KP infections in critically ill patients, based on expert opinions. SOURCES: PubMed search for relevant publications related to the management of KPC-KP infections. CONTENTS: A panel of experts developed a list of 12 questions to be addressed. In view of the current lack of high-level evidence, they were asked to provide answers on the bases of their knowledge and experience in the field. The panel identified several key aspects to be addressed when dealing with KPC-KP in critically ill patients (preventing colonization in the patient, preventing infection in the colonized patient and colonization of his or her contacts, reducing mortality in the infected patient by rapidly diagnosing the causative agent and promptly adopting the best therapeutic strategy) and provided related suggestions that were based on the available observational literature and the experience of panel members. IMPLICATIONS: Diagnostic technologies could speed up the diagnosis of KPC-KP infections. Combination treatment should be preferred to monotherapy in cases of severe infections. For non-critically ill patients without severe infections, results from randomized clinical trials are needed for ultimately weighing benefits and costs of using combinations rather than monotherapy. Multifaceted infection control interventions are needed to decrease the rates of colonization and cross-transmission of KPC-KP.

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.

Antimicrobial prophylaxis in minor and major surgery.

Surgical site infections (SSIs) are a frequent cause of morbidity following surgical procedures. Gram-positive cocci, particularly staphylococci, cause many of these infections, although Gram-negative organisms are also frequently involved. The risk of developing a SSI is associated with a number of factors, including aspects of the operative procedure itself, such as wound classification, and patient-related variables, such as preexisting medical conditions. Antimicrobial prophylaxis (AP) plays an important role in reducing SSIs, especially if patient-related risk factors for SSIs are present. The main components of antimicrobial prophylaxis are: timing, selection of drugs and patients, duration and costs. Compliance with these generally accepted preventive principles may lead to overall decreases in the incidence of these infections. Ideally the administration of the prophylactic agent should start within 30 minutes from the surgical incision. The duration of the AP should not exceed 24 hours for the majority of surgical procedures. The shortest effective period of prophylactic antimicrobial administration is not known and studies have demonstrated that post-surgical antibiotic administration is unnecessary. Furthermore, there were no proven benefits in multiple dose regimens when compared to single-dose regimens. The choice of an appropriate prophylactic antimicrobial agent should be based primarily on efficacy and safety. Broad spectrum antibiotics should be avoided due to the risk of promoting bacterial resistance. Cephalosporins are the most commonly used antibiotics in surgical prophylaxis; specifically, cefazolin or cefuroxime are mainly used in the prophylaxis regimens for cardio-thoracic surgery, vascular surgery, hip or knee arthroplasty surgery, neurosurgical procedures and gynecologic and obstetric procedures. A review of the prophylactic regimens regarding the main surgical procedures is presented.

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.

Anti-neutrophil cytoplasmic antibodies in echinococcus granulosus hydatid disease.

The authors studied the presence of ANCA, evaluated by indirect immunofluorescence (IIF) and ELISA for anti-lactoferrin (LF), and anti-myeloperoxidase antibodies (anti-MPO), in sera of 69 patients with cystic echinococcosis (CE). According to Caremani's classification, 27 patients were considered to have active cysts and 42 patients were considered to have inactive cysts. ANCA were detected in 9 out of 27 patients (33.3%) with active cysts and in 3 out of 42 patients (7.1%) with inactive cysts. Differences between the two groups were statistically significant (P < 0.05). Anti-LF antibodies were found in seven patients (10.14%) and anti-MPO antibodies in ten patients (14.5%).

Infective endocarditis in patients with human immunodeficiency virus infection.

OBJECTIVES: To determine the clinical features, sites of involvement, bacteriological findings, and outcome of infective endocarditis (IE) in patients with HIV infection. PATIENTS AND METHODS: All patients with diagnosis of IE admitted to 54 infectious disease centres in Italy over a 15-year period (1984-1999) were reviewed, and 895 cases fulfilled the Duke criteria for definite diagnosis of IE. Data were collected with regard to the clinical, laboratory, and demographic characteristics of patients, as well as results of blood cultures and data on clinical outcome. RESULTS: There were 108 episodes of IE in 105 HIV-infected patients. The mean age of patients was 30.1 years, and the commonest predisposing condition was intravenous drug use (94.3%). Staphylococci were the predominant organisms (60.2%), and the tricuspid valve was the most frequently involved site of infection (51.9%). Left-sided heart involvement (45.4%) and multivalvular involvement (17.6%) were also frequently observed. The greater frequency of S. aureus affecting the tricuspid valve vs. other valves was statistically significant (P<0.001). Six patients (5.9%) underwent surgery, and one (16.7%) of them died. Ninety-five (94.1%) patients were treated medically, and 17 (17.9%) of them died. Overall mortality rate was 17.8%. Any left-sided heart involvement was predictive of an increased risk of death if compared with any right-sided heart involvement (P< 0.004). The mortality rate among HIV-infected patients was higher in those with CD4 cell counts below 200/mm(3). CONCLUSIONS: IE in HIV-infected patients, for the most part intravenous drug users, is more commonly localized to the right side of the heart; however, mixed or left-side valvular infections are frequent. Severe immunosuppression and left-side valvular involvement are associated with a greater risk for mortality.

Myths, misconceptions and mixed cryoglobulinemia associated with HCV infection.

The delineation of the association of HCV infection with mixed cryoglobulinemia has provided new insight into the etiology and pathogenesis of this extrahepatic manifestation of the infection. Yet very little evidence has been obtained thus far on the specific roles of virus in production of the monoclonal rheumatoid factors responsible for classic type II cryoglobulins and the associated clinical manifestations. The problematic areas of investigation that have in some instances generated misconceptions due to lack of data are reviewed. These include the prevalence and heterogeneity of mixed cryoglobulins; clinical manifestations such as liver cirrhosis, membranoproliferative glomerulonephritis, autoimmunity, progression of cryoglobulinemia from type III to type II, development of B cell malignancies; determination of lineages based on immunoglobulin gene utilization; and the anti-viral treatment of patients with mixed cryoglobulinemia.