Outcomes and Predictors of Mortality in Patients With KPC-Kp Infections Treated With Meropenem Vaborbactam: An Observational Multicenter Study.

Background: Meropenem-vaborbactam is a recent and promising option for the treatment of KPC-producing Klebsiella pneumoniae (KPC-Kp) infections, including those resistant to ceftazidime-avibactam. Methods: We conducted a retrospective analysis of observational data from 19 Italian hospitals on use and outcomes of patients treated with meropenem-vaborbactam for at least ≥24 hours for KPC-Kp infections. Crude and propensity-weighted multiple Cox regression models were performed to ascertain risk factors independently associated with 30-day mortality. Results: The cohort included 342 adults with bloodstream infections (n = 172) and nonbacteremic infections (n = 170), of which 107 were lower respiratory tract infections, 30 were complicated urinary tract infections, and 33 were infections involving other sites. Most infections (62.3%) were managed with meropenem-vaborbactam monotherapy, or in combination with at least 1 other active drug (usually fosfomycin, tigecycline, or gentamicin) (37.7%). The 30-day mortality rate was 31.6% (108/342). In multiple Cox regression model, 30-day mortality was independently associated with septic shock at infection onset, Charlson comorbidity index ≥ 3, dialysis, concomitant COVID-19, and INCREMENT score ≥ 8. Administration of meropenem-vaborbactam within 48 hours from infection onset was a negative predictor of mortality. All predictors, except administration of meropenem-vaborbactam within 48 hours, remained significant when the multiple Cox regression model was repeated after adjustment for the propensity score for receipt of combination therapy. Conclusions: Despite the limits of a retrospective study, the data derived from this multicenter cohort provide additional evidence on the efficacy of meropenem-vaborbactam in treating severe KPC-Kp infections, even when used as monotherapy.

A Difficult Case of Ventriculitis in a 40-Year-Old Woman with Acute Myeloid Leukemia.

Ventriculitis and nosocomial meningitis caused by carbapenem-resistant Gram-negative and vancomycin-resistant Gram-positive bacteria represent a growing treatment challenge. A case of ventriculitis and bacteremia caused by carbapenem-resistant, KPC-producing Klebsiella pneumoniae and vancomycin-resistant Enterococcus faecium in a young woman with acute leukemia who was successfully treated with meropenem/vaborbactam (MVB), rifampicin, and linezolid is described in this paper. This case report emphasizes the importance of a multidisciplinary strategy, including infectious focus control, for the treatment of device-associated central nervous system (CNS) infections from multidrug-resistant bacteria. Considering the novel resistance patterns, more research on drug penetration into the central nervous system, as well as on the necessity of association therapies, is needed.

Screening for Latent Tuberculosis Infection in People Living with HIV: TUBHIVIT Project, a Multicenter Italian Study.

BACKGROUND: The coexistence of HIV infection and latent tuberculosis infection (LTBI) presents a significant public health concern due to the increased risk of tuberculosis (TB) reactivation and progression to active disease. The multicenter observational cohort study, TUBHIVIT, conducted in Italy from 2017 to 2023, aimed to assess the prevalence of LTBI among people living with HIV (PLHIV) and their outcomes following LTBI screening and therapy initiation. METHODS: We performed a prospective study in five referral centers for HIV care in Italy. PLHIV who consented Tto participate underwent QuantiFERON-TB Gold Plus and clinical, microbiological, and radiological assessments to exclude subclinical tuberculosis, as opportune. PLHIV diagnosed with LTBI who started chemoprophylaxis were followed until the end of therapy. RESULTS: A total of 1105 PLHIV were screened for LTBI using the QuantiFERON-TB Gold Plus test, revealing a prevalence of 3.4% of positive results (38/1105). Non-Italy-born individuals exhibited a significantly higher likelihood of testing positive. Thirty-one were diagnosed with LTBI, 1 showed active subclinical TB, and 6 were lost to follow-up before discriminating between latent and active TB. Among the PLHIV diagnosed with LTBI, 83.9% (26/31) started chemoprophylaxis. Most individuals received 6-9 months of isoniazid-based therapy. Of the 26 PLHIV commencing chemoprophylaxis, 18 (69.2%) completed the therapy, while 3 discontinued it and 5 were still on treatment at the time of the analysis. Adverse events were observed in two cases, while in one case the patient refused to continue the treatment.

Ceftazidime-Avibactam as Osteomyelitis Therapy: A Miniseries and Review of the Literature.

Bone and joint infections (BJIs) caused by multidrug-resistant gram-negative bacteria are becoming a concern due to limited therapeutic options. Although not approved for these indications, an ever-growing amount of evidence supports the efficacy and safety of ceftazidime-avibactam as a therapy for osteomyelitis and prosthetic joint infections. Here, we present three cases of difficult-to-treat resistant Pseudomonas aeruginosa osteomyelitis that were successfully treated with ceftazidime-avibactam alone or in combination therapy with fosfomycin and amikacin. Ceftazidime-avibactam was prescribed at a daily dose of 2.5 g every 8 h for 42 days in all cases. One potential drug-related adverse effect was observed, i.e., Clostridioides difficile infection, which occurred after fourteen days of treatment with ceftazidime-avibactam.

The Use of Intravenous Fosfomycin in Clinical Practice: A 5-Year Retrospective Study in a Tertiary Hospital in Italy.

Fosfomycin in intravenous (IV) formulation has re-emerged as a valuable tool in the treatment of multi-drug resistant (MDR) and extensively drug-resistant (XDR) infections because of its broad spectrum of antibacterial action and pharmacokinetic characteristics. This retrospective study aimed to evaluate how fosfomycin was used in patients admitted to the Polyclinic of Palermo between January 2017 and July 2022. Clinical indications, therapeutic associations, clinical outcomes, and any side effects were analyzed. Intravenous fosfomycin was used in 343 patients, 63% male, with a mean age of 68 years (range 15-95). Urinary tract infections (UTIs) and hospital-acquired pneumonia (HAP) were the main indications for treatment (19% and 18% of the total cases, respectively), followed by skin and soft tissue infections and sepsis. IV fosfomycin was administered in combination with other antibacterial agents, the most common of which were ceftazidime/avibactam (35%), meropenem (17%), and colistin (14%). Nineteen patients received it as monotherapy for UTIs. About 66% had resolution of the infectious process with clinical remission (cure or discharge). Electrolyte disturbances occurred in 2.6% and gastrointestinal symptoms occurred in 2.9%. The data showed that IV fosfomycin is a safe and effective therapeutic option in the treatment of infections with multidrug-resistant microorganisms.

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.

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.

Thromboembolic Events in Patients with Influenza: A Scoping Review.

INTRODUCTION: Influenza is an acute respiratory infection that usually causes a short-term and self-limiting illness. However, in high-risk populations, this can lead to several complications, with an increase in mortality. Aside from the well-known extrapulmonary complications, several studies have investigated the relationship between influenza and acute cardio and cerebrovascular events. Reviews of the thromboembolic complications associated with influenza are lacking. OBJECTIVES: the study aims to conduct a scoping review to analyze the epidemiological and clinical characteristics of patients suffering from influenza and thromboembolic complications. MATERIALS AND METHODS: A computerized search of historical published cases using PubMed and the terms "influenza" or "flu" and "thrombosis", "embolism", "thromboembolism", "stroke", or "infarct" for the last twenty-five years was conducted. Only articles reporting detailed data on patients with thromboembolic complications of laboratory-confirmed influenza were considered eligible for inclusion in the scoping review. RESULTS: Fifty-eight cases with laboratory documented influenza A or B and a related intravascular thrombosis were retrieved. Their characteristics were analyzed along with those of a patient who motivated our search. The localizations of thromboembolic events were pulmonary embolism 21/58 (36.2%), DVT 12/58 (20.6%), DVT and pulmonary embolism 3/58 (5.1%), acute ischemic stroke 11/58 (18.9%), arterial thrombosis 4/58 (6.8%), and acute myocardial infarction 5/58 (8.6%). DISCUSSION: Our findings are important in clarifying which thromboembolic complications are more frequent in adults and children with influenza. Symptoms of pulmonary embolism and influenza can be very similar, so a careful clinical evaluation is required for proper patient management, possible instrumental deepening, and appropriate pharmacological interventions, especially for patients with respiratory failure.

Third Case of Visceral Leishmaniasis in COVID-19: Mini Review Article.

BACKGROUND: In the currently ongoing coronavirus pandemic, coinfections with unrelated life-threatening febrile conditions may pose a particular challenge to clinicians. Leishmaniasis is a zoonosis that may present general symptoms, including fever, malaise, and arthralgia, rendering it indistinguishable from COVID-19. METHODS: In this paper, we aim to draw attention to this issue and analyze the clinical characteristics of the coinfection SARS-CoV-2/Leishmania through a systematic review of the literature. We were motivated by the observation of the first case of visceral leishmaniasis and COVID-19 in a paediatric patient. CONCLUSION: Our case is a reminder for healthcare providers to consider the diagnosis of visceral leishmaniasis in patients presenting with febrile syndrome in endemic regions during the COVID-19 pandemic.

MIS-C and co-infection with P. vivax and P. falciparum in a child: a clinical conundrum.

BACKGROUND: The ongoing Coronavirus Disease 2019 (COVID-19) epidemic represents an unprecedented global health challenge. Many COVID-19 symptoms are similar to symptoms that can occur in other infections. Malaria should always be considered in patients with SARS-CoV-2 infection returning from endemic areas. CASE PRESENTATION: We present the first case of multisystem inflammatory syndrome (MIS-C) and Plasmodium vivax-falciparum and SARS-CoV2 coinfection in children. Despite clearance of parassitaemia and a negative COVID-19 nasopharyngeal PCR, the patient's clinical conditions worsened. The World Health Organization (WHO) criteria were used to make the diagnosis of MIS-C. Treatment with intravenous immunoglobulins and methylprednisolone was effective. CONCLUSIONS: This case emphasizes the importance of considering malaria diagnosis in patients returning from endemic areas, even in the COVID 19 era. Malaria and SARS-CoV2 co-infection may increase the risk of MIS-C, for which early detection is critical for proper management.

Superinfections caused by carbapenem-resistant Enterobacterales in hospitalized patients with COVID-19: a multicentre observational study from Italy (CREVID Study).

Objectives: To describe clinical characteristics and outcomes of COVID-19 patients who developed secondary infections due to carbapenem-resistant Enterobacterales (CRE). Methods: Retrospective observational study including COVID-19 patients admitted to 12 Italian hospitals from March to December 2020 who developed a superinfection by CRE. Superinfection was defined as the occurrence of documented bacterial infection >48 h from admission. Patients with polymicrobial infections were excluded. Demographic, clinical characteristics and outcome were collected. Isolates were classified as KPC, metallo-ß-lactamase (MBL) and OXA-48-producing CRE. A Cox regression analysis was performed to identify factors independently associated with 30 day mortality. Results: Overall, 123 patients (median age 66 years, IQR 59-75) were included. The majority of infections occurred in the ICU (81, 65.9%), while 42 (34.1%) in medical wards. The most common types of infection were bloodstream infections (BSI) (n = 64, 52%), followed by urinary-tract infections (UTI) (n = 28, 22.8%), hospital-acquired/ventilator-associated pneumonia (HAP/VAP) (n = 28, 22.8%), intra-abdominal infections (n = 2, 1.6%) and skin infections (n = 1, 0.8%). Sixty-three (51.2%) infections were caused by KPC-, 54 (43.9%) by MBL-, and 6 (4.8%) by OXA-48-producing CRE. Thirty-day mortality was 33.3% (41/123). On Cox regression analysis, HAP/VAP compared with UTI (HR 7.23, 95% CI 2.09-24.97, P = 0.004), BSI compared with UTI (HR 3.96, 95% CI, 1.33-11.77, P = 0.004), lymphopenia on admission (HR 3, 95% CI 1.44-6.26, P = 0.003) and age (HR 1.05, 95% CI 1.02-1.08, P = 0.002) were predictors of 30 day mortality. Conclusions: Superinfections by CRE were associated with high risk of 30 day mortality in patients with COVID-19. HAP/VAP was the strongest predictor of death in these patients.

A case of disseminated BCG infection in a daughter of Italian immigrants in Switzerland.

Bacillus Calmette-Guérin (BCG) is a vaccine against tuberculosis and contains a live, attenuated strain of Mycobacterium bovis as its essential constituent. Being a live, attenuated strain with potential pathogenicity, BCG can cause different complications, both near the inoculation site and through blood dissemination, especially in patients with immunodeficiency. IFN-γR1 deficiency is an autosomal recessively inherited immunodeficiency characterized by predisposition to infections with intracellular pathogens, in particular mycobacteria. We report a rare case of chronic osteomyelitis lasting 30 years due to BCG in a woman with IFN-γR1 deficiency who had previous clinical history of multi-organ BCGitis. Diagnosis of chronic osteomyelitis was confirmed by an 18-fluorine fluorodeoxyglucose positron emission tomography combined with CT scan (18F-FDG PET/CT). In children with a history of BCG vaccination and chronic unexplained infections, a clinical suspicion of BCG-related disease must arise, and a reason of immunodeficiency should be sought.

Rickettsiosis with Pleural Effusion: A Systematic Review with a Focus on Rickettsiosis in Italy.

BACKGROUND: Motivated by a case finding of Mediterranean spotted fever (MSF) associated with atypical pneumonia and pleural effusion in which Rickettsia conorii subsp. israelensis was identified by molecular methods in the pleural fluid, we wanted to summarize the clinical presentations of rickettsiosis in Italy by systematic research and to make a systematic review of all the global cases of rickettsiosis associated with pleural effusion. METHODS: For the literature search, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology was followed. We chose to select only the studies published in last 25 years and confirmed both with serological and molecular assays. RESULTS: Human cases of rickettsiosis in Italy were reported in 48 papers describing 2831 patients with very different clinical presentations; the majority was MSF accounted to R. conorii and was reported in Sicily. Pleural effusion associated with infection with microorganisms belonging to Rickettsiales was described in 487 patients. It was rarely associated with microorganisms different from O. tsutsugamushi; also rarely, cases of scrub typhus were reported outside Southeast Asia and in the largest majority, the diagnosis was achieved with serology. CONCLUSIONS: MSF, especially when caused by R. conorii subsp. israelensis, may be a severe disease. A high index of suspicion is required to promptly start life-saving therapy. Pleural effusion and interstitial pneumonia may be part of the clinical picture of severe rickettsial disease and should not lead the physician away from this diagnosis.

A severe case of Israeli spotted fever with pleural effusion in Italy.

BACKGROUND: The most common Italian rickettsiosis is Mediterranean Spotted Fever (MSF). MSF is commonly associated with a symptom triad consisting of fever, cutaneous rash, and inoculation eschar. The rash is usually maculopapular but, especially in severe presentations, may be petechial. Other typical findings are arthromyalgia and headache. Herein, we describe for the first time an unusual case of Israeli spotted fever (ISF) associated with interstitial pneumonia and pleural effusion in which R. conorii subsp. israelensis was identified by molecular methods in the blood, as well as in the pleural fluid. CASE PRESENTATION: A 72-year-old male presented with a 10-day history of remittent fever. On admission, the patient's general condition appeared poor with confusion and drowsiness; the first assessment revealed a temperature of 38.7°, blood pressure of 110/70 mmHg, a blood oxygen saturation level of 80% with rapid, frequent, and superficial breathing using accessory muscles (28 breaths per minute), and an arrhythmia with a heart rate of 90 beats per minute. qSOFA score was 3/3. Chest CT revealed ground-glass pneumonia with massive pleural effusion. Petechial exanthema was present diffusely, including on the palms and soles, and a very little eschar surrounded by a violaceous halo was noted on the dorsum of the right foot. Awaiting the results of blood cultures, broad-spectrum antibiotic therapy with meropenem 1 g q8h, ciprofloxacin 400 mg q12h, and doxycycline 100 mg q12h was initiated. Doxycycline was included in the therapy because of the presence of petechial rash and fever, making us consider a diagnosis of rickettsiosis. This suspicion was confirmed by the positivity of polymerase chain reaction on whole blood for R. conorii subsp. israelensis. Thoracentesis was performed to improve alveolar ventilation. R. conorii subsp. israelensis was again identified in the pleural fluid by PCR technique. On day 4 the clinical condition worsened. Blood exams showed values suggestive of secondary hemophagocytic lymphohistiocytosis; 4 out of 8 diagnostic criteria were present and empirical treatment with prednisone was started resulting in a gradual improvement in general condition. CONCLUSIONS: Israeli spotted fever may be a severe disease. A high index of suspicion is required to promptly start life-saving therapy. Pleural effusion and interstitial pneumonia may be part of the clinical picture of severe rickettsial disease and should not lead the physician away from this diagnosis.

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.

Clinical use of BCG and its complications: a case series.

Bacillus Calmette-Guérin (BCG), a live, attenuated strain of Mycobacterium bovis, is the essential constituent of the vaccine against tuberculosis and the gold-standard adjuvant treatment for urothelial cancer of the bladder. Being a live, attenuated strain with a potential pathogenic action, bacilli can cause several complications, both locally near the inoculation site and remotely through blood dissemination. BCG-related disease can represent a side effect of anti-TB vaccination in patient with congenital or acquired immunodeficiency or a complication of the therapeutic schedule in oncologic patients. Herein we report five cases of BCG-related disease which occurred at the Infectious Diseases Department of the University Hospital of Palermo during a five-year period from January 2014 to December 2019.

Postpartum listeria meningitis.

Listeria monocytogenes is a small Gram positive, intracellular bacillus known to cause a foodborne disease in immunocompromised patients and other high-risk groups. The infection that usually is asymptomatic or resembles a mild influenza like disease, in some risk groups can cause meningitis and brain abscesses. In pregnant women, L. monocytogenes may lead to abortion or delivery of an acutely ill infant. We describe a case of L. monocytogenes meningitis occurred in a young puerpera without immunological disorders or other risk factors. We think that because the puerperium is accompanied by the same physiological changes in immune response that features pregnancy, a higher infectious risk should be considered during this period of woman's life. Therefore, an empiric antimicrobial therapy also for listeriosis should be promptly started in meningitis that arises in post-partum period so to achieve the best outcome of the infection.

Irreversible acute renal failure and cholestatic hepatitis following therapy with indomethacin in an HIV-naive patient with pericarditis: a case report.

The most frequent clinical manifestation of cardiovascular diseases in patients with AIDS is pericarditis. Indomethacin is a well tolerated non-steroidal inflammatory drug (NSAID) widely used in the treatment of pericarditis but it can provoke acute renal failure. Tenofovir has also been associated with chronic renal dysfunction. Liver damage can occur during treatment with NSAIDs. We describe the first case of acute renal failure and cholestatic hepatitis occurring in an HIV-naive patient with pericarditis starting HAART (highly active antiretroviral therapy) and assuming indomethacin and antibiotic therapy for opportunistic infections (OIs) at the same time. Based on our case we suggest that attention be paid to drug-drug interactions in such patients.

Disseminated tuberculosis in a patient treated with a JAK2 selective inhibitor: a case report.

BACKGROUND: Primary myelofibrosis is a myeloproliferative disorder characterized by bone marrow fibrosis, abnormal cytokine expression, splenomegaly and anemia. The activation of JAK2 and the increased levels of circulating proinflammatory cytokines seem to play an important role in the pathogenesis of myelofibrosis. Novel therapeutic agents targeting JAKs have been developed for the treatment of myeloproliferative disorders. Ruxolitinib (INCB018424) is the most recent among them. CASE PRESENTATION: To our knowledge, there is no evidence from clinical trials of an increased risk of tuberculosis during treatment with JAK inhibitors. Here we describe the first case of tuberculosis in a patient treated with Ruxolitinib, a male with a 12-year history of chronic idiopathic myelofibrosis admitted to our Institute because of fever, night sweats, weight loss and an enlarging mass in the left inguinal area for two months. CONCLUSION: Treatment with Ruxolitinib may have triggered the reactivation of latent tuberculosis because of an inhibition of Th1 response. Our case highlights the importance of an accurate screening for latent tuberculosis before starting an anti-JAK 2 treatment.