Fatal respiratory infection due to ST308 VIM-1-producing Pseudomonas aeruginosa in a lung transplant recipient: case report and review of the literature.

BACKGROUND: Data regarding the prevalence of metallo-ß-lactamases (MBLs) among Pseudomonas aeruginosa isolates in cystic fibrosis patients are scarce. Furthermore, there is limited knowledge on the effect of MBL production on patient outcomes. Here we describe a fatal respiratory infection due to P. aeruginosa producing VIM-type MBLs in a lung transplant recipient and the results of the subsequent epidemiological investigation. CASE PRESENTATION: P. aeruginosa isolates collected in the index patient and among patients temporally or spatially linked with the index patient were analyzed in terms of antibiotic susceptibility profile and MBL production. Whole-genome sequencing and phylogenetic reconstruction were also performed for all P. aeruginosa isolates producing VIM-type MBLs. A VIM-producing P. aeruginosa strain was identified in a lung biopsy of a lung transplant recipient with cystic fibrosis. The strain was VIM-1-producer and belonged to the ST308. Despite aggressive treatment, the transplant patient succumbed to the pulmonary infection due to the ST308 strain. A VIM-producing P. aeruginosa strain was also collected from the respiratory samples of a different cystic fibrosis patient attending the same cystic fibrosis center. This isolate harbored the blaVIM-2 gene and belonged to the clone ST175. This patient did not experience an adverse outcome. CONCLUSIONS: This is the first description of a fatal infection due to P. aeruginosa producing VIM-type MBLs in a lung transplant recipient. The circulation of P. aeruginosa isolates harboring MBLs pose a substantial risk to the cystic fibrosis population due to the limited therapeutic options available and their spreading potential.

Humoral and cell-mediated immune responses to BNT162b2 vaccine against SARS-CoV-2 in people with cystic fibrosis.

People with cystic fibrosis (pwCF) were considered to be clinically vulnerable to COVID-19 and were therefore given priority in the vaccination campaign. Vaccines induced a humoral response in these patients that was comparable to the response observed among the general population. However, the role of the cell-mediated immune response in providing long-term protection against SARS-CoV-2 in pwCF has not yet been defined. In this study, humoral (antibody titre) and cell-mediated immune responses (interferon-γ release) to the BNT162b2 vaccine were measured at different time points, from around 6-8 months after the 2nd dose and up to 8 months after the 3rd dose, in 118 CF patients and 26 non-CF subjects. Subjects were sampled between November 2021 and September 2022 and followed-up for breakthrough infection through October 2022. pwCF mounted a cell-mediated response that was similar to that observed in non-CF subjects. Low antibody titres (<1st quartile) were associated with a higher risk of breakthrough infection (HR: 2.39, 95 % CI: 1.17-4.88), while there was no significant association with low INF-γ levels (<0.3 IU/mL) (HR: 1.38, 95 % CI: 0.64-2.99). Further studies are needed in subgroup of pwCF receiving immunosuppressive therapy, such as organ transplant recipients. This data is important for tailoring vaccination strategies for this clinically vulnerable population.

Effects of insulin therapy optimization with sensor augmented pumps on glycemic control and body composition in people with cystic fibrosis-related diabetes.

Objective: Cystic fibrosis (CF)-related diabetes (CFRD) resulting from partial-to-complete insulin deficiency occurs in 40-50% of adults with CF. In people with CFRD, poor glycemic control leads to a catabolic state that may aggravate CF-induced nutritional impairment and loss of muscle mass. Sensor augmented pump (SAP) therapy may improve glycemic control as compared to multiple daily injection (MDI) therapy. Research design and methods: This non-randomized clinical trial was aimed at evaluating the effects of insulin therapy optimization with SAP therapy, combined with a structured educational program, on glycemic control and body composition in individuals with insulin-requiring CFRD. Of 46 participants who were offered to switch from MDI to SAP therapy, 20 accepted and 26 continued the MDI therapy. Baseline demographic and clinical characteristics were balanced between groups using a propensity score-based overlap weighting procedure and weighted mixed-effects regression models were used to estimate changes in study outcomes. Results: After 24 months changes in HbA1c were: -1.1% (-12.1 mmol/mol) (95% CI: -1.5; -0.8) and -0.1% (-1 mmol/mol) (95% CI: -0.5; 0.3) in the SAP and MDI therapy group, respectively, with a between-group difference of -1.0 (-10 mmol/mol) (-1.5; -0.5). SAP therapy was also associated with a decrease in mean glucose (between group difference: -32 mg/dL; 95% CI: -44; -20) and an increase in TIR (between group difference: 19.3%; 95% CI 13.9; 24.7) and in fat-free mass (between group difference: +5.5 Kg, 95% CI: 3.2; 7.8). Conclusion: Therapy optimization with SAP led to a significant improvement in glycemic control, which was associated with an increase in fat-free mass.

In vitro antimicrobial activity of ceftolozane/tazobactam against Pseudomonas aeruginosa and other non-fermenting Gram-negative bacteria in adults with cystic fibrosis.

OBJECTIVES: Pulmonary exacerbations in patients with cystic fibrosis (CF) caused by chronic Gram-negative bacterial infections are associated with reduced survival. These pathogens are usually treated with repeated courses of systemic antimicrobial agents. However, there is associated emergence of multidrug-resistant (MDR) pathogens. Ceftolozane/tazobactam (C/T) is a novel cephalosporin/ß-lactamase inhibitor combination that has been demonstrated to have good activity against MDR Pseudomonas aeruginosa. METHODS: In this study, C/T was compared with other commonly used intravenous antimicrobial agents against 193 non-fermenting Gram-negative bacteria isolated from CF sputum specimens, including P. aeruginosa, Achromobacter xylosoxidans, Stenotrophomonas maltophilia and Burkholderia cenocepacia. Minimum inhibitory concentrations (MICs) to C/T were determined by standard Etest assay and were interpreted according to current European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines. RESULTS: C/T had good in vitro antimicrobial activity against CF clinical isolates of P. aeruginosa in comparison with other antimicrobial agents, with the exception of colistin. C/T also had activity against S. maltophilia but was not active against B. cenocepacia or A. xylosoxidans. CONCLUSION: C/T showed excellent in vitro activity against P. aeruginosa CF clinical isolates. This antimicrobial agent is a potential therapeutic option when presented with challenging MDR P. aeruginosa and S. maltophilia exacerbations. Further clinical experience and trials in CF are required to determine the place of C/T in clinical practice.

Knowledge and attitudes on influenza vaccination among Italian physicians specialized in respiratory infections: an Italian Respiratory Society (SIP/IRS) web-based survey.

INTRODUCTION: Influenza epidemics are one of the main causes of morbidity and mortality worldwide. Influenza vaccination is considered the most important public health intervention to prevent seasonal influenza infection. European health authority policies focus on patient protection by vaccinating both these subjects and their care-givers, including health-care workers (HCWs). The aim of this survey is to investigate knowledge about influenza vaccination and intention to get vaccinated among Italian HCWs who take care patients with respiratory disease. METHODS: An anonymous web-based survey was addressed to members of the Italian Respiratory Society (IRS). RESULTS: Among the 1,776 IRS members who have been invited to the survey, 144 (8.1%) completed the survey (97 men; median age 59 years; 85.4% Respiratory Disease). The vast majority recommended vaccination to all their patients (81%). More than two thirds of respondents considered influenza vaccination safe for immunocompromised patients. More than 50% of respondents underwent seasonal influenza vaccination in 2015 and 68% declared the intention to undergo vaccination in 2016 epidemic season. Reasons for having vaccination mainly referred to 'protect oneself from influenza' (63%), 'protect patients' (31%) or household members' (6%). The main reasons for vaccination refusal were 'lack of time' (45%), 'concerns about side effects' (22%), 'do not get influenza easily and/or not afraid of influenza infection' (22%) and 'disagreement with indication of vaccination for HCWs' (9%). CONCLUSIONS: The promotion of better knowledge and attitude towards influenza vaccination among Italian specialists remains an unmet goal and should be addressed by appropriate multifaceted interventions.

Effect of timepidium bromide on the motor activity of the sphincter of Oddi: manometric evaluation of intracholedochal pressure.

The intracholedochal pressure changes induced by timepidium bromide were studied in 12 patients who had undergone surgery because of gall bladder stones and were receiving transient external bile drainage by the Kehr method. Cholangiomanometric examination, carried out under basal conditions and after an intravenous dose of 15 mg timepidium bromide, revealed a statistically significant decrease in mean intracholedochal pressure in all 12 patients. It is concluded that timepidium bromide is likely to exert a direct action on the sphincter of Oddi, decreasing its basal tone and thus causing a decrease in intracholedochal pressure.

[Defecography and manometry in the postoperative follow-up of patients treated with colo-anal anastomosis by the Parks technique for neoplasm stenosis of the rectum]. / Defecografia e manometria nel follow-up postoperatorio di pazienti sottoposti a colo-ano anastomosi secondo Parks per stenosi neoplastica del retto.

The Authors report 15 cases of patients with adenocarcinoma of the rectum who were treated using Park's resection. Morphofunctional parameters are evaluated 3 months after surgery using defecography and manometry before the closure of the neostoma and the reactivation of the ano-rectal canal. Opaque defecography enables the morphology and dimensions of the anal canal to be examined together with modifications to the area between the rectum and the anal canal, and the impression of the pubo-rectal sling. In conclusion these data confirm the importance of surgery, whereas the correlation between defecographic and manometric results allows the functional recovery "ad integrum" of the area to be checked.

Primary resection with and without anastomosis for perforation of acute diverticulitis.

The results of management of perforated large bowel diverticulitis were retrospectively studied over a 7-year period. 38 patients underwent operation, 20 for generalized peritonitis, 12 for local peritonitis, 5 for colovesical fistula and 1 for colovaginal fistula. The mean age of patients was 63 years (range 30-85 years). Depending on the symptoms, the spreading of the peritonitis and associated cardiovascular and pulmonary disease and diabetes mellitus, 4 types of operation were performed: primary left hemicolectomy and anastomosis with and without defunctioning colostomy, Hartmann procedure, suture and drainage with diverting colostomy. The overall mortality was 10.5%: resection and primary anastomosis entailed 3.8% mortality (1 case), while 3 deaths were observed in the 8 patients group having underwent an Hartmann procedure (37.5%). Drainage and/or diverting colostomy performed in 5 patients entailed no hospital mortality, but was followed by a 80% complication rate, requiring reoperation and several hospital admissions. The low mortality and morbidity rates obtained in the group having primary resection and anastomosis encourage wider application of this operation for perforated acute diverticulitis. Even the Hartmann procedure allows removal of the diseased colon but in a great proportion of cases reconstitution of continuity is not performed; nevertheless staged operation entailing major mortality and morbidity, expose these aged patients to remarkable hazard. Prerequisite of safe primary excision and anastomosis is vigorous intraperitoneal lavage and drainage, by the case associated to on table large bowel irrigation if concomitant obstruction is present.

Emergency surgery of complicated colonic diverticulitis.

Colon diverticular disease is an increasingly frequent disorder especially in Western populations characterized by high living standards. In 30-40% of subjects over 60 years of age barium enema detects the presence of diverticula in the sigma. 10-20% of patients affected by colon diverticular disease develop complications such as inflammation or haemorrhage and 20-30% of these patients undergo surgery (60% of patients aged less than 40). Emergency surgery is performed in 50% of cases and it is currently burdened by high mortality rates. We decided to review our cases history to clarify the indication for emergency surgery, the appropriateness to resect the diseased bowel tract and to perform colic anastomosis at the time of emergency resection.

[Preliminary results of a new technique for inguinal hernia repair]. / Risultati preliminari di una nuova plastica per la riparazione dell'ernia inguinale.

BACKGROUND: An original technique for the treatment of inguinal hernia is described: this operative technique consists of a Marlex (mono-filament knitted polypropylene) mesh sutured in the preperitoneal space under the fascia trasversalis. METHODS: A total of 202 hernioplasties have been treated: 100 of these have been controlled after six months to detect complications and recurrencies. RESULTS: One recurrency (1%) was found. No previous selection of patients was done. The mesh-repair is simple, rapid, and causes less discomfort than conventional sutured herniorraphy. This technique is compared with the other tension-free mesh hernioplasties. CONCLUSIONS: This operative technique is a prophylaxis for the femoral hernia described as later complication of other techniques.

[Preoperative colonic lavage and one-stage excision-anastomosis in obstruction of the left colon]. / Le lavage colique per-opératoire et la résection-anastomose en un temps dans l'obstruction du côlon gauche.

In a retrospective series of 95 patients requiring emergency surgery for distal colonic obstruction, primary bowel resection followed by immediate anastomosis after intraoperative colonic irrigation was performed. Carcinoma was the cause of obstruction in 81 cases (85%); 13 patients had diverticulitis, and 1 had sigmoid volvulus. The technique of on-table lavage was similar to that described by Dudley in 1980: a caecostomy tube was used in 86 patients (90%) and was removed on the tenth postoperative day. 4 patients died, none from complications of anastomotic leakage. There were three anastomotic leakages (3.1%) and 10 radiologic leaks were observed. 3 patients were reoperated. The mean hospital stay was 23 days. The results of this study suggest that intraoperative colonic irrigation is an effective method, enabling the surgeon to perform primary anastomosis with reasonable safety after emergency resection of selected distal colonic lesions.

[Economic burden and clinical course of HIV infection and AIDS today: how the variation of natural history, available treatments, and strictly related costs play a role in needs of health care]. / Peso economico ed evoluzione dell'infezione da HIV e dell'AIDS oggi: come le modifiche della storia naturale, delle terapie disponibili e dei costi ad esse più strettamente connessi si ripercuotono sulle necessità assistenziali.

In order to provide an updated balance of the evolution of the natural history of HIV infection, the major clinical end-points of disease morbidity and mortality were compared with the progressively increasing use of highly active antiretroviral therapy (HAART), in a cohort of patients followed by our tertiary care centre in an eight-year period including both the pre-HAART and the HAART era. Although direct expenditures for antiretroviral agents reached even 99.8% of overall costs related to drugs and blood derivatives at our entire unit in the year 2000, a clear shift towards outpatient assistance of HIV infection was realized during recent years, leading to an increased and greatly varied spectrum of infectious diseases hospitalized at our inpatient and Day-Hospital units. Due to the significant reduction of inpatient expenditures, even the elevated costs of management of HIV disease based on HAART and periodic virological and immunological monitoring are expected to remain cost-effective, at least during the next few years.

[Extended lymphadenectomy in carcinoma of the right colon]. / La linfoadenectomia estesa nel carcinoma del colon destro.

The Authors report on a retrospective study concerning 49 patients treated for a modified Dukes' stage B, C or D right colon cancer. A potentially curative right hemicolectomy with extended lymphadenectomy was performed. Locally advanced disease was treated by "en bloc" resection. Two (4.1%) patients died after surgery, in other 2 (4.1%) cases major postoperative complications were registered. Microscopic examination of the surgical specimens showed lymph node metastases in 44.9% of the cases: in this subgroup a metastatic involvement of the main (III level) nodal groups was detected in 22.7% of the patients. The Authors conclude that extended lymph node dissection does not increase postoperative complications and may play a role in the treatment of right colon cancer. A not negligible group of patients may be understaged or receive inadequate surgical treatment when submitted to traditional right colectomy.