Successful Antiviral Treatment with Direct-Acting Antivirals for Hepatitis C Virus Infection during Peritransplant Period in a Kidney Transplant Recipient.

Introduction. Hepatitis C virus (HCV) infection continues to represent a poor prognostic factor in kidney transplant (KTx) patients. New direct-acting antiviral agents (DAA) have dramatically changed the therapy management for HCV, showing promising results in terms of sustained virologic response. Timing for DAA therapy in HCV positive kidney waitlist patients continues to be controversial, and caution is recommended due to the potential difficult immunosuppressant dose adjustments, particularly in the early posttransplant period. We report a case of a KTx performed during antiviral DAA therapy. Report of Case. Patient was a 44-year-old man suffering from chronic HCV hepatitis associated with end-stage kidney disease (ESRD), waitlisted for a second KTx as a sensitized patient (panel-reactive antibody peak 85%) in March 2019. Four months later, antiviral DAA therapy was started (glecaprevir/pibrentasvir 300 mg/120 mg daily, for 8 weeks). After 30 days, a left kidney was offered and, given the good compatibility, we decided to proceed with KTx without discontinuing the DAA therapy. A standard straightforward kidney transplant was performed. Immunosuppression included thymoglobulin and prednisone for induction and tacrolimus and mycophenolate for maintenance. After a transient delay graft function, creatinine levels progressively decreased. From postoperative day 3, tacrolimus reached target levels and remained stable. No episodes of acute rejection occurred. The 8-week DAA therapy was carried out without interruption. All HCV-RNA level controls resulted undetectable. On postoperative day 15, the patient was discharged and remains in healthy condition with normal renal function and HCV negative after 18 months of follow-up. Discussion. In this case, DAA therapy during the perioperative KTx period was well tolerated and effective. If confirmed, patients should not necessarily be suspended from the waiting list during DAA therapy for HCV eradication.

Flexible cystoscopy for ureteral stent removal without antimicrobial prophylaxis. A prospective observational study.

OBJECTIVE: Flexible cystoscopy for ureteral stent removal after ureteroscopy is widely performed. In this scenario, the real need for antimicrobial prophylaxis is still uncertain. Aim of this study is to determine the urinary tract infections rate after 4 weeks from outpatient flexible cystoscopies for ureteral stent removal without antimicrobial prophylaxis. PATIENTS AND METHODS: A prospective observational study was performed between November 2017 and August 2018 in a single, high-volume Institution.Risk factors for UTIs were recorded. Immediately before cystoscopy, each patient submitted a voided urine specimen. Antibiotics were not given before or after cystoscopy. About 7 and 28 days after cystoscopy all the patients underwent abdomen US, urine analysis and culture, and clinical evaluation to assess possible symptoms of UTI. RESULTS: A total of 192 patients were enrolled in the study, 76 patients (39.2%) were female. Median age was 55 years [IQR 47- 68]. Median BMI was 24.2 [22.9-26.7]. Eighteen patients (9.4%) had asymptomatic bacteriuria before cystoscopy and 39 (20.3%) had positive culture at 7 days. About 21 patients (10.9%) were diagnosed with febrile UTI in the 28 days FU period. The 28.6 % of the Febrile patients had asymptomatic bacteriuria before the stent removal (p < 0.001), this group was slightly older (p = 0.085) and with higher BMI (p = 0.036).Forty-eight patients had positive urine culture at 7 days, of whom 27 (14.1%) were asymptomatic and were classified as asymptomatic bacteriuria. Multivariate analysis shows that only high BMI and bacteriuria before the procedure were significantly associated with developing a febrile UTI, none of the other risk factors was significant. CONCLUSION: Our data show a high rate of UTI after flexible cystoscopies for ureteral stent removal without antimicrobial prophylaxis especially in patients with asymptomatic bacteriuria, in those with high BMI and in the elderly; in these subgroups, antimicrobial prophylaxis should be recommended.

Tocilizumab and steroid treatment in patients with COVID-19 pneumonia.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) can lead to respiratory failure due to severe immune response. Treatment targeting this immune response might be beneficial but there is limited evidence on its efficacy. The aim of this study was to determine if early treatment of patients with COVID-19 pneumonia with tocilizumab and/or steroids was associated with better outcome. METHODS: This observational single-center study included patients with COVID-19 pneumonia who were not intubated and received either standard of care (SOC, controls) or SOC plus early (within 3 days from hospital admission) anti-inflammatory treatment. SOC consisted of hydroxychloroquine 400mg bid plus, in those admitted before March 24th, also darunavir/ritonavir. Anti-inflammatory treatment consisted of either tocilizumab (8mg/kg intravenously or 162mg subcutaneously) or methylprednisolone 1 mg/kg for 5 days or both. Failure was defined as intubation or death, and the endpoints were failure-free survival (primary endpoint) and overall survival (secondary) at day 30. Difference between the groups was estimated as Hazard Ratio by a propensity score weighted Cox regression analysis (HROW). RESULTS: Overall, 196 adults were included in the analyses. They were mainly male (67.4%), with comorbidities (78.1%) and severe COVID-19 pneumonia (83.7%). Median age was 67.9 years (range, 30-100) and median PaO2/FiO2 200 mmHg (IQR 133-289). Among them, 130 received early anti-inflammatory treatment with: tocilizumab (n = 29, 22.3%), methylprednisolone (n = 45, 34.6%), or both (n = 56, 43.1%). The adjusted failure-free survival among tocilizumab/methylprednisolone/SOC treated patients vs. SOC was 80.8% (95%CI, 72.8-86.7) vs. 64.1% (95%CI, 51.3-74.0), HROW 0.48, 95%CI, 0.23-0.99; p = 0.049. The overall survival among tocilizumab/methylprednisolone/SOC patients vs. SOC was 85.9% (95%CI, 80.7-92.6) vs. 71.9% (95%CI, 46-73), HROW 0.41, 95%CI: 0.19-0.89, p = 0.025. CONCLUSION: Early adjunctive treatment with tocilizumab, methylprednisolone or both may improve outcomes in non-intubated patients with COVID-19 pneumonia.

Kidney transplantation from an HIV-positive cadaveric donor.

Kidney transplantation is the gold-standard therapy for select HIV-positive patients with ESRD. Since the Italian Ministry of Health defined the guidelines for organ donation from HIV-positive persons in 2018, we report the first case of renal transplantation from an HIV-positive cadaveric donor in two HIV-positive recipients in Italy. The donor was a 50-year-old male, deceased due to post-anoxic encephalopathy, with a history of HIV infection in HAART, undetectable viral load, and HCV-related chronic hepatitis that had been previously treated. The first recipient was a 59-year-old female with a prior history of drug addiction, and she suffered from ESRD secondary to HIV nephropathy. The patient followed preoperative HAART with a good viral response and undetectable HIV viral load. She also had a history of HCV-related chronic hepatitis that had been successfully treated. The right kidney was uneventfully transplanted. The patient developed an asymptomatic reinfection of endogenous BK virus. The second recipient was a 41-year-old male with ESRD secondary to polycystic kidney disease. The patient was HIV-positive in HAART, with a good viro-immunologic response and an undetectable HIV viral load. He suffered from a severe form of hemophilia A and HCV-related chronic hepatitis, which had been previously treated with undetectable HCV RNA. The left kidney was uneventfully transplanted. At the end of follow-up, both patients had a healthy condition with stable renal function, a persistently good viral response and undetectable HIV and HCV viral loads. These encouraging preliminary results seem to confirm the safety and effectiveness of kidney transplantation from select HIV-positive donors.

Impact of carbapenem-resistant Klebsiella pneumoniae (CR-KP) infections in kidney transplantation.

BACKGROUND: Carbapenem-resistant Klebsiella pneumoniae (CR-KP) infections in solid organ transplant patients are progressively increasing and are associated with worse outcomes, although potential risk factors and therapeutic strategies are still not well defined. METHODS: We conducted a retrospective matched-pair analysis in which we compared 26 recipients CR-KP-positive after kidney transplantation (KT) with 52 CR-KP-negative patients transplanted in the same period, during a CR-KP outbreak that occurred in our hospital. Twenty-one patients (80%) received a combined antibiotic treatment. At the end of the follow-up, of the 26 CR-KP infected patients, 11 (42.3%) experienced at least one episode of re-infection, 9 (34.6%) remained colonized, and 6 (23.0%) had a symptomatic infection. Two of the 11 patients with re-infection died, while 9 were colonized at the end of the study. RESULTS: A significantly better patient (P = .043) and graft (P < .001) survival was observed in CR-KP-negative patients. Univariate analysis identified the following variables as potential risk factors associated with CR-KP infection after KT: lower body mass index (P = .020); higher creatinine levels at post-transplant days 7 (P = .009), 15 (P = .026), and 30 (P = .019); longer hospital stay (P = .007); longer cold ischemia time (P = .004); delayed graft function (P = .020); and higher Clavien-Dindo score (P = .006). CONCLUSION: The study confirmed that a CR-KP positivity may affect the outcome of a kidney transplant population. In severe CR-KP infections with sepsis, a combined antibiotic treatment seems to be advisable.

Fatal Donor-Derived Carbapenem-Resistant Klebsiella pneumoniae Infection in a Combined Kidney-Pancreas Transplantation.

Carbapenem-resistant Klebsiella pneumoniae (CR-KP) infections in solid organ transplant recipients are associated with high morbidity and mortality. We report a case of a fatal donor-derived CR-KP infection in a combined kidney-pancreas transplant. Given the short interval of time between donor hospitalization and organ procurement, information concerning the donor CR-KP positivity arrived only 72 hours after transplant. Based on this experience, we believe that knowledge of the donor's CR-KP status should be mandatory before procurement and, if positive, pancreas donation should be contraindicated.

Unusual Extrapulmonary Rhodococcus Equi Infection in a Kidney Transplant Patient.

Rhodococcus equi is a well-recognized pathogen in veterinary medicine that can also affect immuno-compromised human subjects. The most common clinical features in humans include necrotizing pneumonia with subacute pulmonary disease, progressive cough, chest pain and fever. We report a case of a 49-year-old kidney transplant patient who developed a Rhodococcus equi infection characterized by multiple abscesses of the soft tissues and muscles without any respiratory manifestation. Combining specific antibiotic therapy and surgical management of the abscesses without immunosuppression discontinuation led to a complete recovery of both patient and graft.

Diagnostic and therapeutic appropriateness in bone and joint infections: results of a national survey.

The impact of infectious diseases (ID) specialist consultation in the management of many types of bacterial infections has been fully demonstrated but not for bone and joint infections (BJIs). Nineteen ID Italian centres collected of data from June 2009 to May 2012. Italian guidelines (2009) were used to determine the appropriateness of the diagnostic and therapeutic process of BJIs before and after consulting an ID specialist. Data on 311 patients were collected: 111 cases of prosthetic joint infection, 99 osteomyelitis, 64 spondylodiscitis and 37 fixation device infection. A significant increase of microbiological investigations, imaging techniques and blood inflammation markers were noted after consulting the ID specialist. Moreover, inappropriateness of treatment duration, dosage, and number of administrations significantly decreased after consultation. Infectious disease specialist intervention in the management of BJIs significantly increases the appropriateness both in performing instrumental and laboratory analysis, but especially in determining the correct therapy.

[Pneumocystis jiroveci and cytomegalovirus pneumonia in patients with alcoholic hepatic cirrhosis]. / Polmonite da Pneumocystis jiroveci e Cytomegalovirus in pazienti con cirrosi epatica alcolica.

We have described a fatal case of interstitial pneumonia with pleuritis in woman, 54 years old, suffered from end stage liver disease caused by ethanolic hepatic cirrhosis. Broncholavage microbiological culture was negative but biomolecular assays with polymerase chain reaction demonstred Pneumocystis jiroveci and Cytomegalovirus. She died despite aetiological therapy with cotrimoxazole and gancyclovir. Immunodeficiency of the delayed immune response, related to the severe liver disease and ethanol use, explains the occurrence of these opportunistic infections in ethanolic cirrhotic patients too.

Clinical and virological survey of patients with hepatitis B surface antigen in an Italian region: clinical considerations and disease burden.

The aim of this study was to determine the prevalence of hepatitis B virus (HBV) infection in an Italian region, Liguria (1,572,000 inhabitants), by means of a network of 12 referral centers for liver diseases. All patients with HBV surface antigen followed throughout 2006 were included. Personal data, infectious status with risk factors, other non-infectious risk factors for liver disease, clinical status, and treatment were the questionnaire. Four hundred forty-five patients (71% male) were evaluated. Their median age was 48 years (range 5-84), and 83.4% were of Italian origin. Community-acquired infection was the principal mode of HBV transmission (82.5%), followed by previous intravenous drug use (9.4%), perinatal transmission (6.3%), and transfusion-associated transmission (1.8%). Hepatitis B e-antigen was present in 20.4% of the patients, while co-infections with hepatitis D virus and/or hepatitis C virus and/or human immunodeficiency virus (HIV) were observed in 18.7% of the patients. Chronic active hepatitis was present in 62.5% of the patients, cirrhosis in 13.5%, hepatocellular carcinoma in 2.2%, and 21.8% of the patients were inactive carriers of HBV. In all, 42.5% of the patients were treated with interferon or lamivudine and/or adefovir-dipivoxil. Forty-nine patients were co-infected with HIV (86% on highly active antiviral therapy). Nevertheless, this study identified only 2.2% of the expected patients with HBV. Hence, it has to be reasoned that few potential infectious or treatable patients are referred to liver disease centers. HBV infection is still an underestimated health problem, and few potential infectious or treatable patients are referred to tertiary centers.

Functionally relevant decreases in activatory receptor expression on NK cells are associated with pulmonary tuberculosis in vivo and persist after successful treatment.

Correlates for the initiation of Mycobacterium tuberculosis hominis (Mth) replication from latency are needed in order to improve Mth control. In order to analyze if perturbations of peripheral NK cells may be associated with exit from Mth latency, sequential patients with newly diagnosed lung tuberculosis (TB) were studied. Peripheral NK cells were analyzed by cytofluorometry, in vitro culture and functional assays. At the onset of lung TB, imbalances in NK cell subsets were evident. Decreased CD56(bright)CD16(+/-) subsets with significantly compromised NKp30 and NKp46 expression and with specifically decreased gamma-IFN production upon triggering were evident. These features were not completely restored when purified NK cells were cultured in vitro. Culture supplementation with alpha-IFN increased only NKp30 expression in TB and healthy donors. Extensive peripheral NK cell triggering was evident in these patients, as shown by the expression of NK cell activation markers and of the lymph node-homing chemokine receptor CCR7 on CD16(+) CD56(dull) cells. Significant persistence of decreased NKp30 and NKp46 after successful treatment with a standard four-drug regimen was detected after full recovery. NK cell function is deeply affected in patients at the onset of pulmonary TB. The involvement of multiple activatory receptors may provide a relevant contribution to the spread of mycobacteria exiting from latency.

A significant proportion of patients with chronic hepatitis B who are candidates for antiviral treatment are untreated: A region-wide survey in Italy.

BACKGROUND: Between 350 and 400 million people worldwide have chronic hepatitis B virus (HBV) infection, and in Italy this figure is 1% to 2% in the general population. In clinical practice, however, it is not known how many patients chronically infected by HBV and eligible for antiviral therapy are not treated. AIM: To characterize the clinical picture of untreated HBV patients, and to assess whether current experts' recommendations for treatment are actually applied. METHODS: We evaluated 362 patients chronically infected by HBV alone who were followed for at least 1 year at tertiary referral centers in Liguria region, Italy. Patients' data were evaluated on the basis of the Panel of Experts algorithm for the management of HBV [ie, HBV DNA levels > or =20,000 IU/mL in hepatitis B e antigen (HBeAg)-positive patients, HBV DNA levels > or =2000 IU/mL in HBeAg-negative patients, and evidence of biochemical and/or histologic activity of disease in both groups]. RESULTS: One-hundred and sixteen viremic chronic hepatitis B disease patients were not on antiviral therapy (33 HBeAg positive, 83 HBeAg negative). Serum HBV DNA was > or =20,000 IU/mL and > or =2000 IU/mL in 32 HBeAg-positive and 54 HBeAg-negative patients, respectively, and disease was present in 59 of these 86 patients. Treatment was not indicated in 10 of 59 patients, and had been planned in 8 (4 HBeAg positive), thus 84% potential treatment candidates (41 of 49 patients) were not treated. CONCLUSIONS: Evaluation of a large series of patients chronically infected by HBV alone identified a significant proportion of patients who are actually untreated despite being potential candidates for antiviral therapy.

Bloodstream infections caused by multidrug-resistant Klebsiella pneumoniae producing the carbapenem-hydrolysing VIM-1 metallo-beta-lactamase: first Italian outbreak.

OBJECTIVES: To investigate the first Italian outbreak of bloodstream infections caused by multidrug-resistant (MDR) Klebsiella pneumoniae producing metallo-beta-lactamase (MBL), which occurred in three wards of one large tertiary-care hospital in Genoa, Italy, from September 2004 to March 2005. METHODS: MBL production was screened by an imipenem-EDTA disc synergy test and confirmed by a conventional hydrolysis test. Antibiotic susceptibility was determined by broth microdilution or disc diffusion. PFGE was used to study the genetic relatedness of isolates. PCR and sequencing were carried out to identify the beta-lactamase genes and to analyse the genetic context of the MBL gene. Outer membrane protein (OMP) profiles were analysed by SDS-PAGE. RESULTS: Nine cases of bloodstream infections caused by an MDR strain of K. pneumoniae producing the VIM-1 MBL and the SHV-5 extended-spectrum beta-lactamase (ESBL) were identified. The isolates exhibited various carbapenem resistance levels (imipenem MICs ranged from 4 to 64 mg/L) and were resistant to other beta-lactams, fluoroquinolones, trimethoprim/sulfamethoxazole and chloramphenicol. The isolate with the highest imipenem MIC also lacked the k36 OMP. The bla(VIM-1) gene cassette was part of the variable region of a class 1 integron that also included an aac(6')-IIc cassette. The ESBL and MBL genes were transferable by conjugation. CONCLUSIONS: This is the first report on the emergence of an MDR strain of K. pneumoniae producing the VIM-1 MBL, causing an outbreak of bloodstream infections in an Italian hospital. The strain evolved through OMP alterations generating a mutant with increased carbapenem resistance.

Incidence and risk factors associated with pressure ulcers among patients with HIV infection.

OBJECTIVE: To assess the incidence of and risk factors for pressure ulcers among patients with advanced human immunodeficiency virus type 1 (HIV-1) infection. DESIGN: Multicenter trial that included 1258 consecutive patients infected with HIV-1 who had 1815 admissions to 16 acute care infectious disease units in Italy. METHODS: Data were collected for demographic, clinical, immunologic, and virologic parameters. The chi-square test was used to compare categorical variables, and the Student t test was used for continuous variables. Univariate analysis was performed to examine possible risk factors for pressure ulcers by computing odds ratios; a multiple logistic regression model was used to obtain adjusted estimates of odds ratios while accounting for all possible risk factors. RESULTS: The incidence of pressure ulcers was 2.31 per 100 admissions, 3.33 per 100 patients, and 1.06 per 1000 patient days. All stages of pressure ulcers were represented in the sample: 7 Stage I (15.9%), 24 Stage II (54.5%), 8 Stage III (18.2%), and 5 Stage IV (11.4%). Multivariate analyses showed that being female, length of hospitalization, and clinical markers of HIV infection were independently associated with pressure ulcers. Mortality rates were 50% among patients with pressure ulcers and 7.2% among patients without pressure ulcers (P <.0001), with an attributable mortality rate of 42.8% and an odds ratio of 12.96 (95% confidence interval 6.99-24.22). CONCLUSIONS: A higher incidence of pressure ulcers was found in patients infected with HIV-1 when compared with noninfected patients. Because a longer hospitalization may increase the risk of developing a pressure ulcer, practitioners should be aware of the clinical conditions that may prolong a patient's hospital stay. Aggressive preventive strategies should be implemented to decrease the complications associated with pressure ulcers among patients infected with HIV-1.

Nosocomial bloodstream infections among human immunodeficiency virus-infected patients: incidence and risk factors.

To assess the incidence of nosocomial bloodstream infections (NBSIs) in human immunodeficiency virus (HIV)-infected patients, and to analyze the main associated risk factors, we performed a 1-year multicenter prospective study of patients with advanced HIV infection who were consecutively admitted to 17 Italian infectious diseases wards. As of May 1999, a total of 65 NBSIs (4.7%) occurred in 1379 admissions, for an incidence of 2.45 NBSIs per 1000 patient-days. Twenty-nine NBSIs were catheter-related bloodstream infections, with a rate of 9.6 central venous catheter-associated infections per 1000 device-days. Multivariate analysis indicated that variables independently associated with NBSIs included active injection drug use, a Karnofsky Performance Status score of <40, presence of a central venous catheter, and length of hospital stay. Mortality rates were 24.6% and 7.2% among patients with and without NBSIs, respectively (P<.00001). In the era of highly active antiretroviral therapy, NBSIs continue to occur frequently and remain severe and life-threatening manifestations.