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.

Qualitative and quantitative change of the tolerance to liposomal amphotericin B triggered by biofilm maturation in C. parapsilosis.

Candida parapsilosis is an emerging opportunistic pathogen present in both clinical and natural environment, with a strong frequency of biofilm forming strains. While the drugs active against biofilm are rare, liposomal amphotericin B is credited with an antibiofilm activity in some opportunistic species of the genus Candida. Using freshly isolated strains from hospital environment, in this paper we could show the prevalence of biofilm forming vs. nonbiofilm forming strains. The former displayed a large variability in terms of biofilm biomass and metabolic activity. Liposomal amphotericin B minimum inhibitory concentration (MIC) of planktonic cells was below the breakpoint, whereas the sessile cells MIC (SMIC) was 1 or 2 orders of magnitude above the planktonic MIC. When the drug was applied to freshly attached cells, that is, biofilm in formation, the MIC (called SDMIC) was even below the MIC value. All resistance metrics (MIC, SMIC, and SDMIC) were quite variable although no correlation could be detected between them and the metrics used to quantify biofilm activity and biomass production. These findings demonstrate that young biofilm cells are even more susceptible than planktonic cells and that early treatments with this drug can be beneficial in cases of prosthesis implantation or especially when there is the necessity of a CVC reimplantation during a sepsis.

Daily bathing with 4% chlorhexidine gluconate in intensive care settings: a randomized controlled trial.

OBJECTIVES: To investigate whether daily bathing with a soap-like solution of 4% chlorhexidine (CHG) followed by water rinsing (CHGwr) would decrease the incidence of hospital-acquired infections (HAI) in intensive care settings. METHODS: Randomized, controlled trial; infectious diseases specialists were blinded to the intervention status. All patients admitted to the Intensive Care Unit (ICU) and to the Post-operative Cardiosurgical Intensive Care Unit (PC-ICU) of the University Hospital of Perugia were enrolled and randomized to the intervention arm (daily bathing with 4% CHGwr) or to the control arm (daily bathing with standard soap). The incidence rate of acquisition of HAI was compared between the two arms as primary outcome. We also evaluated the incidence of bloodstream infections (BSI), central-line-associated BSI (CLABSI), ventilator-associated pneumonia (VAP) and catheter-associated urinary tract infections (CAUTI), and 4% CHGwr safety. RESULTS: In all, 449 individuals were enrolled, 226 in treatment arm and 223 in control arm. Thirty-four individuals of the 226 (15%) and 57 (25.6%) suffered from at least an HAI in the intervention and control arms, respectively (p 0.008); 23.2 and 40.9 infections/1000 patient-days were detected in the intervention arm and control arm, respectively (p 0.037). The incidence of all bloodstream infections (BSI plus CABSI) was significantly reduced in the intervention arm (9.2 versus 22.6 infections/1000 patient-days, p 0.027); no differences were observed in the mortality between the two arms. CONCLUSIONS: Daily bathing with 4% CHGwr significantly reduced HAI incidence in intensive care settings. CLINICALTRIAL. GOV REGISTRATION: NCT03639363.

Safety and efficacy of tigecycline in complicated and uncomplicated pelvic inflammatory disease.

OBJECTIVE: Tigecycline is a glycylcycline antimicrobial structurally related to minocycline, with a wide spectrum of activity that includes anaerobes and typical and atypical microorganisms causing pelvic inflammatory disease (PID). This study aimed to evaluate efficacy and safety of tigecycline in complicated PID and un-complicated PID after the failure of first-line antibiotic therapy. PATIENTS AND METHODS: Between May 2014 and April 2016 at the 2nd Unit of Obstetrics and Gynecology, Santa Chiara Hospital of Pisa a pilot study on 20 women with mild/moderate PID after the failure of first-line antibiotic therapy and on 8 women with complicated PID was conducted. The treatment protocol was 10-day course of tigecycline, with a loading dose of 100 mg intravenously (i.v.) at day one and then 50 mg IV twice daily. The primary endpoint was to evaluate tigecycline's efficacy in terms of clinical response to test-of-cure (TOC) at the end of therapy and 30 days after the last dose. Clinical response during therapy and safety were analyzed as well. RESULTS: A total of 28 women were enrolled, and 25 patients completed the study protocol, because 3 patients reported adverse drug effects resulting in treatment interruption. PID was mainly caused by Chlamydia, Gardnerella, Mycoplasma/Ureaplasma. Tigecycline showed a 100% remission of signs and symptoms in patients resistant to first-line antibiotic regimen and in patients with complicated PID. Moreover, tigecycline showed good tolerability and compliance. CONCLUSIONS: Despite the limited sample size, tigecycline seemed an effective and safe treatment for women with complicated/resistant PID. Nevertheless, further clinical trials are needed to confirm these results.

Early recognition of methicillin-resistant Staphylococcus aureus surgical site infections using risk and protective factors identified by a group of Italian surgeons through Delphi method.

BACKGROUND: Surgical site infections (SSIs) constitute a major clinical problem in terms of morbidity, mortality, duration of hospital stay, and overall costs. The bacterial pathogens implicated most frequently are Streptococcus pyogenes (S. pyogenes) and Staphylococcus aureus (S. aureus). The incidence of methicillin-resistant S. aureus (MRSA) SSIs is increasing significantly. Since these infections have a significant impact on hospital budgets and patients' health, their diagnosis must be anticipated and therapy improved. The first step should be to evaluate risk factors for MRSA SSIs. METHODS: Through a literature review, we identified possible major and minor risk factors for, and protective factors against MRSA SSIs. We then submitted statements on these factors to 228 Italian surgeons to determine, using the Delphi method, the degree of consensus regarding their importance. The consensus was rated as positive if >80% of the voters agreed with a statement and as negative if >80% of the voters disagreed. In other cases, no consensus was reached. RESULTS: There was positive consensus that sepsis, >2 weeks of hospitalization, age >75 years, colonization by MRSA, and diabetes were major risk factors for MRSA SSIs. Other possible major risk factors, on which a consensus was not reached, e.g., prior antibiotic use, were considered minor risk factors. Other minor risk factors were identified. An adequate antibiotic prophylaxis, laparoscopic technique, and infection committee surveillance were considered protective factors against MRSA SSIs. All these factors might be used to build predictive criteria for identifying SSI due to MRSA. CONCLUSIONS: In order to help to recognize and thus promptly initiate an adequate antibiotic therapy for MRSA SSIs, we designed a gradation of risk and protective factors. Validation, ideally prospective, of this score is now required. In the case of a SSI, if the risk that the infection is caused by MRSA is high, empiric antibiotic therapy should be started after debriding the wound and collecting material for culture.

Assessment of risk factors for candidemia in non-neutropenic patients hospitalized in Internal Medicine wards: A multicenter study.

BACKGROUND: An increasing prevalence of candidemia has been reported in Internal Medicine wards (IMWs). The aim of our study was to identify risk factors for candidemia among non-neutropenic patients hospitalized in IMWs. METHODS: A multicenter case-control study was performed in three hospitals in Italy. Patients developing candidemia (cases) were compared to patients without candidemia (controls) matched by age, time of admission and duration of hospitalization. A logistic regression analysis identified risk factors for candidemia, and a new risk score was developed. Validation was performed on an external cohort of patients. RESULTS: Overall, 951 patients (317 cases of candidemia and 634 controls) were included in the derivation cohort, while 270 patients (90 patients with candidemia and 180 controls) constituted the validation cohort. Severe sepsis or septic shock, recent Clostridium difficile infection, diabetes mellitus, total parenteral nutrition, chronic obstructive pulmonary disease, concomitant intravenous glycopeptide therapy, presence of peripherally inserted central catheter, previous antibiotic therapy and immunosuppressive therapy were factors independently associated with candidemia. The new risk score showed good area under the curve (AUC) values in both derivation (AUC 0.973 95% CI 0.809-0.997, p<0.001) and validation cohort (0.867 95% CI 0.710-0.931, p<0.001). A threshold of 3 leads to a sensitivity of 87% and a specificity of 83%. CONCLUSION: Non-neutropenic patients admitted in IMWs have peculiar risk factors for candidemia. A new risk score with a good performance could facilitate the identification of candidates to early antifungal therapy.

Focus on the prophylaxis, epidemiology and therapy of methicillin-resistant Staphylococcus aureus surgical site infections and a position paper on associated risk factors: the perspective of an Italian group of surgeons.

BACKGROUND: The aim of this research was to study the epidemiology, microbiology, prophylaxis, and antibiotic therapy of surgical site infections (SSIs), especially those caused by methicillin-resistant Staphylococcus aureus (MRSA), and identify the risk factors for these infections. In Italy SSIs occur in about 5 % of all surgical procedures. They are predominantly caused by staphylococci, and 30 % of them are diagnosed after discharge. In every surgical specialty there are specific procedures more associated with SSIs. METHODS: The authors conducted a systematic review of the literature on SSIs, especially MRSA infections, and used the Delphi method to identify risk factors for these resistant infections. RESULTS: Risk factors associated with MRSA SSIs identified by the Delphi method were: patients from long-term care facilities, recent hospitalization (within the preceding 30 days), Charlson score > 5 points, chronic obstructive pulmonary disease and thoracic surgery, antibiotic therapy with beta-lactams (especially cephalosporins and carbapenem) and/or quinolones in the preceding 30 days, age 75 years or older, current duration of hospitalization >16 days, and surgery with prothesis implantation. Protective factors were adequate antibiotic prophylaxis, laparoscopic surgery and the presence of an active, in-hospital surveillance program for the control of infections. MRSA therapy, especially with agents that enable the patient's rapid discharge from hospital is described. CONCLUSION: The prevention, identification and treatment of SSIs, especially those caused by MRSA, should be implemented in surgical units in order to improve clinical and economic outcomes.

KPC-producing Klebsiella pneumoniae rectal colonization is a risk factor for mortality in patients with diabetic foot infections.

To evaluate the relationship between carbapenemase-producing Klebsiella pneumoniae (KPC-Kp) gut colonization and mortality in diabetic patients with a foot infection (DFI) we performed a single-centre, retrospective, matched case-control study. In the study period, we identified 21 patients with DFI who had KPC-Kp gut colonization and 21 controls. The 90-day mortality rate was significantly higher in patients with colonized guts (47%) than the controls (4%) (p 0.013). A multivariate analysis demonstrated that gut colonization with KPC-Kp was the only independent predictor of mortality: odds ratio 13.33, 95% CI 1.90-272.80, p 0.024. In patients with DFI, KPC-Kp gut colonization appears to be an important risk factor for mortality.

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.

Radiolabelled leucocyte scintigraphy versus conventional radiological imaging for the management of late, low-grade vascular prosthesis infections.

PURPOSE: In this study we evaluated the diagnostic performance of (99m)Tc-HMPAO-leucocyte ((99m)Tc-HMPAO-WBC) scintigraphy in a consecutive series of 55 patients (46 men and 9 women, mean age 71 ± 9 years, range 50 - 88 years) with a suspected late or a low-grade late vascular prosthesis infection (VPI), also comparing the diagnostic accuracy of WBC with that of other radiological imaging methods. METHODS: All patients suspected of having VPI underwent clinical examination, blood tests, microbiology, US and CT, and were classified according to the Fitzgerald criteria. A final diagnosis of VPI was established in 47 of the 55 patients, with microbiological confirmation after surgical removal of the prosthesis in 36 of the 47. In the 11 patients with major contraindications to surgery, the final diagnosis was based on microbiology and clinical follow-up of at least 18 months. RESULTS: (99m)Tc-HMPAO-WBC planar, SPECT and SPECT/CT imaging identified VPI in 43 of 47 patients (20 of these also showed infection at extra-prosthetic sites). In the remaining eight patients without VPI, different sites of infections were found. The use of SPECT/CT images led to a significant reduction in the number of false-positive findings in 37% of patients (sensitivity and specificity 100 %, versus 85.1% and 62.5% for stand-alone SPECT). Sensitivity and specificity were 34% and 75% for US, 48.9% and 83.3% for CT, and 68.1% and 62.5% for the FitzGerald classification. Perioperative mortality was 5.5%, mid-term mortality 12%, and long-term mortality 27%. Survival rates were similar in patients treated with surgery and antimicrobial therapy compared to patients treated with antimicrobial therapy alone (61% versus 63%, respectively), while infection eradication at 12 months was significantly higher following surgery (83.3% versus 45.5%). CONCLUSION: (99m)Tc-HMPAO-WBC SPECT/CT is useful for detecting, localizing and defining the extent of graft infection in patients with late and low-grade late VPI with inconclusive radiological findings. (99m)Tc-HMPAO-WBC SPECT/CT might be used to optimize patient management.

Rapid detection of intestinal carriage of Klebsiella pneumoniae producing KPC carbapenemase during an outbreak.

Two different approaches are described for rapid detection of intestinal carriage of Klebsiella pneumoniae producing KPC-type carbapenemase (KPC-KP), based on PCR amplification of DNA extracts from rectal swabs (K-PCR), and on direct plating of rectal swabs on to MacConkey agar with a meropenem disc and a meropenem plus 3-aminophenylboronic acid disc (direct KPC screening test, DKST). K-PCR and DKST were tested with a total of 101 samples from 65 patients, during an outbreak. Although less sensitive, DKST could detect high-level carriage, which appears to be common among infected and colonised patients, while being very cheap and easy to perform, and requiring only basic facilities.