Donor-derived carbapenem-resistant gram-negative bacterial infections in solid organ transplant recipients: Active surveillance enhances recipient safety.

Donor-derived infections (DDIs) caused by carbapenem-resistant gram-negative bacteria (CR-GNB) in solid organ transplant recipients are potentially life-threatening. In this prospective study, we evaluated the incidence, factors associated with transmission, and the outcome of recipients with unexpected CR-GNB DDIs after the implementation of our local active surveillance system (LASS). LASS provides for early detection of unexpected donor CR-GNB infections, prophylaxis of recipients at high risk, and early diagnosis and treatment of DDIs. Whole genome sequencing confirmed DDI. Among 791 recipients, 38 (4.8%) were at high risk of unexpected CR-GNB DDI: 25 for carbapenem-resistant Enterobacterales (CRE) and 13 for carbapenem-resistant Acinetobacter baumannii (CRAB). Transmission did not occur in 27 (71%) cases, whereas DDIs occurred in 9 of 25 of CRE and 2 of 13 of CRAB cases. Incidence of CR-GNB DDI was 1.4%. Recipients of organs with CR-GNB-positive preservation fluid and liver recipients from a donor with CRE infection were at the highest risk of DDI. There was no difference in length of hospital stay or survival in patients with and without CR-GNB DDI. Our LASS contains transmission and mitigates the negative impacts of CR-GNB DDI. Under well-defined conditions, organs from donors with CR-GNB may be considered after a thorough evaluation of the risk/benefit profile.

Molecular Analysis With 16S rRNA PCR/Sanger Sequencing and Molecular Antibiogram Performed on DNA Extracted From Valve Improve Diagnosis and Targeted Therapy of Infective Endocarditis: A Prospective Study.

BACKGROUND: Molecular analysis (MA) on heart valve (HV) improves the microbiologic diagnosis of infectious endocarditis (IE). The main drawback of MA is the lack of antimicrobial susceptibility information. METHODS: We conducted a prospective cohort observational study of consecutive adult patients from April 2012 to May 2021 who underwent valve surgery at our hospital. The performance of MA, blood cultures (BC) and valve cultures (VC), and the diagnostic and therapeutic impact of MA were evaluated. Molecular antibiogram results were compared to culture-based antimicrobial susceptibility testing (AST). RESULTS: A total of 137 patients with definite IE and 52 patients with no IE were enrolled in the study. Among IE cases BC, VC, and MA were positive in 75 (55%), 30 (22%), and 120 (88%) of IE cases, respectively. Among 62 cases of BC-negative IE (BCNE), 57 achieved diagnosis with MA. MA led to a change of antimicrobial therapy in 92% of BCNE. MA was negative in 100% of patients with no IE. Molecular antibiogram performed on 17 valve specimens that resulted positive for pathogens potential carrier of genes encoding for multidrug resistant mechanisms showed 100% concordance with AST. CONCLUSIONS: MA showed a high specificity and sensitivity in etiological diagnosis of IE. Molecular antibiogram could overcome the major limitation of MA that is the lack of susceptibility testing. We advocate for the inclusion of MA among diagnostic criteria for IE and for a more extensive use of molecular antibiogram when the culture result is negative, and MA is the only positive test.

Mortality Attributable to Bloodstream Infections Caused by Different Carbapenem-Resistant Gram-Negative Bacilli: Results From a Nationwide Study in Italy (ALARICO Network).

BACKGROUND: Our aim was to analyze mortality attributable to carbapenem-resistant (CR) gram-negative bacilli (GNB) in patients with bloodstream infections (BSIs). METHODS: Prospective multicentric study including patients with GNB-BSI from 19 Italian hospitals (June 2018-January 2020). Patients were followed-up to 30 days. Primary outcomes were 30-day mortality and attributable mortality. Attributable mortality was calculated in the following groups: Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacterales, metallo-ß-lactamases (MBL)-producing Enterobacterales, CR-Pseudomonas aeruginosa (CRPA), CR-Acinetobacter baumannii (CRAB). A multivariable analysis with hospital fixed-effect was built to identify factors associated with 30-day mortality. Adjusted OR (aORs) were reported. Attributable mortality was calculated according to the DRIVE-AB Consortium. RESULTS: Overall, 1276 patients with monomicrobial GNB BSI were included: 723/1276 (56.7%) carbapenem-susceptible (CS)-GNB, 304/1276 (23.8%) KPC-, 77/1276 (6%) MBL-producing CRE, 61/1276 (4.8%) CRPA, and 111/1276 (8.7%) CRAB BSI. Thirty-day mortality in patients with CS-GNB BSI was 13.7% compared to 26.6%, 36.4%, 32.8% and 43.2% in patients with BSI by KPC-CRE, MBL-CRE, CRPA and CRAB, respectively (P < .001). On multivariable analysis, age, ward of hospitalization, SOFA score, and Charlson Index were factors associated with 30-day mortality, while urinary source of infection and early appropriate therapy resulted protective factors. Compared to CS-GNB, MBL-producing CRE (aOR 5.86, 95% CI 2.72-12.76), CRPA (aOR 1.99, 95% CI 1.48-5.95) and CRAB (aOR 2.65, 95% CI 1.52-4.61) were significantly associated with 30-day mortality. Attributable mortality rates were 5% for KPC-, 35% for MBL, 19% for CRPA, and 16% for CRAB. CONCLUSIONS: In patients with BSIs, carbapenem-resistance is associated with an excess of mortality, with MBL-producing CRE carrying the highest risk of death.

A case of syphilis associated with immune reconstitution inflammatory syndrome and review of the literature.

BACKGROUND: Immune reconstitution inflammatory syndrome (IRIS) associated with syphilis has rarely been described in HIV-infected patients. Diagnosis can be challenging because it is not always possible to discern it from a recent infection or a worsening of an undiagnosed one. CASE PRESENTATION: An HIV-positive 42-year-old man with a poor compliance history of antiretroviral therapy presented at our unit and complained of ocular symptoms. Ocular syphilis diagnosis was posed after initial misdiagnosing with cytomegalovirus infection, and antiretroviral therapy compliance improved after switching to a bictegravir-based regimen. Despite intravenous (IV) penicillin, we observed an initial worsening with the appearance of new skin lesions, and IRIS syphilis was suspected. In the literature, 14 cases of IRIS syphilis are described, all regarding male patients. Seven were HIV naïve to therapy, and 7 HIV-experienced with poor therapy compliance. Basal syphilis serology was negative in ten, with subsequent seroconversion after the development of IRIS. IRIS-syphilis development was observed after a median time of 28 days from ART initiation; 10 cases were considered "unmasking-IRIS" and 4 "paradoxical-IRIS". Skin and ocular involvement were the most often reported. In most cases, it was not necessary to use a systemic steroid. A good outcome was reported in 12. CONCLUSIONS: Syphilis should be considered in differential diagnosis with other diseases associated with IRIS. A negative syphilis serology before beginning antiretroviral therapy could convey the impression that syphilis has been ruled out. Whereas a high index of suspicion should be maintained when symptoms suggestive of syphilis, such as ocular and skin manifestations, are noticed after therapy has begun.

An emergent infectious disease: Clostridioides difficile infection hospitalizations, 10-year trend in Sicily.

BACKGROUND: Clostridioides difficile is the most common cause of healthcare-associated diarrhoea worldwide and C. difficile infection is an emerging infectious disease. In the US, its rates are monitored trough an active surveillance system, but many European Union member states still lack this, and in Italy no epidemiological data on C. difficile infection are available except for a few single-centre data. AIM: To provide data on the C. difficile infection incidence in Sicily (the biggest and 5th most populous region of Italy) during a 10-year period. METHODS: We revised all the regional standardized discharge forms between 2009 and June 2019 using the code ICD-9 00845 of the International Classification of Diseases, Ninth Revision Clinical Modification, which refers to C. difficile infection with or without complications. RESULTS: 1139 cases of CDI were identified. 97% were adults with a median age of 73.2 years and a male-to-female ratio of 1:1.4. Female patients were older than males and patients who died were older than patients who did not. The main comorbidities were renal disease, diabetes, pneumonia and hypertension. There were 65 reporting hospitals and 86% of cases were provided by level III and II hospitals. Between 2009 and 2019, the incidence increased 40-fold. 81.5% of cases were reported in Medicine Units, Infectious Diseases Units and long-term care facilities. The mean length of stay was 20 days. Mean case fatality rate was 8.3% over the 10-year period. CONCLUSION: Clostridioides difficile infection is a dramatically increasing condition in Sicily. A high-quality surveillance system and shared diagnostic protocols are needed.

Epidemiology and successful containment of a carbapenem-resistant Enterobacteriaceae outbreak in a Southern Italian Transplant Institute.

INTRODUCTION: Carbapenem-resistant enterobacteriaceae (CRE) infections are difficult to treat and pose a serious threat to solid organ transplant (SOT) recipients. At our institute we observed an infection burden in 2012. METHODS: In order to contain the spread of CRE infections, we established a taskforce to implement guidelines suggested by the Centers for Disease Control and Prevention (CDC) for this type of outbreak. Here, we describe the epidemiology of the outbreak in our SOT population, and the effectiveness of such interventions, by comparing levels of CRE hospital-acquired infection (HAI) pre- and post-task force intervention (from January 2009 to December 2012, and from September 2013 to December 2016, respectively) through a linear regression model. RESULTS: In this study, we included 933 patients who underwent a total of 1017 SOT procedures, 286 of whom had a CRE-positive culture (28.8%), of which 65 (22.7% of CRE positive) developed infection. One-year mortality post-SOT was significantly higher in patients with CRE infection. After the taskforce intervention, the CRE HAI rate in SOT showed a significant inverse trend (event rate: -1.28, CI -1.70 to 0.86; P < 0.01). CONCLUSION: In the paucity of treatment options, the application of CDC measures in our SOT institute contributed significantly to containing CRE infections.

Intestinal Involvement in Kawasaki Disease.

OBJECTIVES: To describe a case of Kawasaki disease with intestinal involvement and to analyze other published reports to define clinical characteristics, diagnostic issues, and therapeutic approaches of gastrointestinal involvement in Kawasaki disease. STUDY DESIGN: A computerized search without language restriction was conducted using PubMed and SCOPUS. An article was considered eligible for inclusion in the systematic review if it reported data on patient(s) with intestinal involvement in Kawasaki disease. Our case was also included in the analysis. RESULTS: Thirty-three articles reporting 48 cases of Kawasaki disease with intestinal involvement were considered. Fever, abdominal pain, and vomiting were the most frequent symptoms observed and typical Kawasaki disease signs and symptoms appeared after intestinal complaints in all cases. Plain radiographs, ultrasonography, and computed tomography showed pseudo-obstruction as the most frequent sign of gastrointestinal involvement; 25 patients underwent surgery. Cardiac involvement was documented in 21 cases. All but three patients received medical treatment with immunoglobulin intravenous or aspirin. The outcome was good in 28 patients; 7 patients showed persistence of coronary artery abnormalities; 1 patient developed cyanosis, and later, left hand and forefoot gangrene; 3 patients died. CONCLUSIONS: The diagnosis and treatment of Kawasaki disease might be delayed if intestinal symptoms appear before the characteristic clinical features of Kawasaki disease, thus, increasing the risk of cardiac complications. Furthermore, patients may undergo unnecessary invasive procedures. Pediatricians and pediatric surgeons, therefore, should consider Kawasaki disease among diagnoses in children with fever, abdominal symptoms, and radiologic findings of pseudo-obstruction.

Multisystem Inflammatory Syndrome: A Case in an Adult With Controlled Lymphoma and a Persistent SARS-CoV-2 Infection.

Multisystem inflammatory syndrome (MIS) is a new and rare complication of COVID-19 that usually occurs in children. An increasing number of cases of MIS in adults are described in the literature. The condition is associated with high mortality, and treatment is non-standardized. Clinical pictures are heterogeneous, and diagnosis is very challenging. Here we describe a case of MIS in a 60-year-old man with previous follicular lymphoma treated with obinutuzumab and recent SARS-CoV-2 infections. He complained of an unknown fever and developed pancytopenia during the hospitalization, associated with a general clinical worsening. The patient was successfully treated with intravenous immunoglobulin and steroids.

Hemophagocytic lymphohistiocytosis secondary to histoplasmosis: A case report in a patient with AIDS and recent SARS-CoV-2 infection and minireview.

Here, we describe the case of a naïve HIV late presenter female African patient with progressive disseminated histoplasmosis and a severe life-threatening clinical picture in a non-endemic area. She had not visited Africa in the past decade. She developed a reactive hemophagocytic lymphohistiocytosis and an acute psychiatric disorder. Histoplasmosis was diagnosed after two bone marrow biopsies. Therapy with liposomal amphotericin B resulted in rapid and progressive improvements in blood examinations and clinical conditions, including the disappearance of psychiatric disorders. The characteristics of our case were compared with those of all other cases of hemophagocytic syndrome secondary to histoplasmosis in HIV-positive patients reported in PubMed. In conclusion, clinicians outside endemic areas should evaluate histoplasmosis as a cause of severe clinical picture, especially in a patient with a travel history to an endemic area, even after many years, considering the possible reactivation of latent infection.

Cefiderocol Efficacy in a Real-Life Setting: Single-Centre Retrospective Study.

The current carbapenem-resistant gram-negative bacteria (CR-GN) treatment guidelines lack strong evidence about cefiderocol (CFD) efficacy against CR-GN, especially CRAB. The study's purpose is to evaluate the effectiveness of CFD in a real-life setting. We made a single-center retrospective study of 41 patients who received CFD in our hospital for several CR-GN infections. Bloodstream infections (BSI) affected 43.9% (18/41) of patients, while CRAB affected 75.6% (31/41) of isolated CR-GN patients. Thirty-days (30-D) all-causes mortality affected 36.6% (15/41) of patients, while end-of-treatment (EOT) clinical cure affected 56.1% (23/41). Finally, microbiological eradication at EOT affected 56.1% (23/41) of patients. Univariate and multivariate analysis showed that septic shock is an independent factor associated with mortality. Subgroup analyses showed no difference in CFD effectiveness between monotherapy and combination therapy.

Clostridioides difficile Infection in an Italian Tertiary Care University Hospital: A Retrospective Analysis.

Clostridioides difficile infection (CDI) is a significant cause of morbidity and mortality, mostly in frail patients. Notification is not mandatory in Italy, and data on incidence, risk of death, and recurrence are lacking. The purpose of this study was to determine CDI incidence and risk factors for mortality and recurrence. The "ICD-9 00845" code in hospital-standardized discharged forms (H-SDF) and microbiology datasets were used to retrieve CDI cases at Policlinico Hospital, Palermo between 2013 and 2022. Incidence, ward distribution, recurrence rate, mortality, and coding rate were considered. The risk of death and recurrence was predicted through multivariable analysis. There were 275 CDIs, 75% hospital-acquired, the median time between admission and diagnosis was 13 days, and the median stay was 21 days. Incidence increased from 0.3 to 5.6% (an 18.7-fold increase) throughout the decade. Only 48.1% of cases were coded in H-SDF. The rate of severe/severe-complicated cases increased 1.9 times. Fidaxomicin was used in 17.1% and 24.7% of cases overall and since 2019. Overall and attributable mortalities were 11.3% and 4.7%, respectively. Median time between diagnosis and death was 11 days, and recurrence rate was 4%. Bezlotoxumab was administered in 64% of recurrences. Multivariable analysis revealed that only hemodialysis was associated with mortality. No statistically significant association in predicting recurrence risk emerged. We advocate for CDI notification to become mandatory and recommend coding CDI diagnosis in H-SDF to aid in infection rate monitoring. Maximum attention should be paid to preventing people on hemodialysis from getting CDI.

Kawasaki disease recurrence in the COVID-19 era: a systematic review of the literature.

Kawasaki disease (KD) is a vasculitis of unknown origin of small and medium caliber blood vessels, especially involving coronary arteries and is the leading cause of acquired heart disease in childhood in developed countries. Although rarely, it can recur: most recurrences occur within 2 years of the initial episode. No data are available on incidence of recurrent KD in Europe and multiple recurrences are rarely seen. We reviewed the medical literature on Kawasaki disease recurrence and reported a new case of Kawasaki disease recurrence in a child with SARS-CoV-2 infection. We believe that in our case SARS Cov2 acted as a trigger capable to determine, in a genetically susceptible individual, a second recurrence of the disease. In the Covid-19 era we affirm the importance for Kawasaki disease to be tested for SARS Cov2 infection.

Combination of aztreonam, ceftazidime-avibactam and amikacin in the treatment of VIM-1 Pseudomonas aeruginosa ST235 osteomyelitis.

We describe a challenging case of patient with metallo-beta-lactamase-producing Pseudomonas aeruginosa sternal osteomyelitis following aortic valve replacement with biological prosthesis. The strain exhibited a multidrug-resistance phenotype carrying the blaVIM-1 gene and belonged to the high-risk clone sequence type ST235. The patient was successfully treated with surgical debridement plus antibiotic therapy with ceftazidime/avibactam, aztreonam, and amikacin. Time-kill curves showed that this triple antibiotic combination at 1 × MIC was strongly synergic after 8 h, achieving 99.9% killing and maintaining this until 48 h.

Malassezia restricta Pneumonia in Solid Organ Transplant Recipients: First Report of Two Cases.

Emerging fungal infections are a major challenge in solid organ transplantation (SOT) and are associated with high morbidity and mortality. We report two cases of Malassezia restricta pneumonia in SOT recipients. Infections were diagnosed with molecular analysis and histology. Patients were treated with antifungal therapy and have fully recovered.

Risk Factors for Candidemia After Open Heart Surgery: Results From a Multicenter Case-Control Study.

BACKGROUND: Candida species are among the most frequent causative agents of health care-associated bloodstream infections, with mortality >40% in critically ill patients. Specific populations of critically ill patients may present peculiar risk factors related to their reason for intensive care unit admission. The primary objective of the present study was to assess the predictors of candidemia after open heart surgery. METHODS: This retrospective, matched case-control study was conducted in 8 Italian hospitals from 2009 to 2016. The primary study objective was to assess factors associated with the development of candidemia after open heart surgery. RESULTS: Overall, 222 patients (74 cases and 148 controls) were included in the study. Candidemia developed at a median time (interquartile range) of 23 (14-36) days after surgery. In multivariable analysis, independent predictors of candidemia were New York Heart Association class III or IV (odds ratio [OR], 23.81; 95% CI, 5.73-98.95; P < .001), previous therapy with carbapenems (OR, 8.87; 95% CI, 2.57-30.67; P = .001), and previous therapy with fluoroquinolones (OR, 5.73; 95% CI, 1.61-20.41; P = .007). Crude 30-day mortality of candidemia was 53% (39/74). Septic shock was independently associated with mortality in the multivariable model (OR, 5.64; 95% CI, 1.91-16.63; P = .002). No association between prolonged cardiopulmonary bypass time and candidemia was observed in this study. CONCLUSIONS: Previous broad-spectrum antibiotic therapy and high NYHA class were independent predictors of candidemia in cardiac surgery patients with prolonged postoperative intensive care unit stay.

Fusarium keratoplasticum infection in an HIV-infected patient.

Fusarium infections are very rare in HIV-infected patients, even in patients in advanced stages of immunosuppression. All the reported cases in the literature are of disseminated infection, and with poor outcomes despite prompt and appropriate treatment. To the best of our knowledge, this is the first report of a localized infection with Fusarium keratoplasticum in an HIV-positive patient, successfully treated with a combination of antifungal therapy and surgical removal of the focus.