Trends in hospital acquired New Delhi metallo-beta-lactamase-producing Enterobacterales in Tuscany (Italy) from 2019 to 2021: impact of the COVID-19 pandemic.

OBJECTIVES: In Tuscany, Italy, New Delhi metallo-beta-lactamase-producing carbapenem-resistant Enterobacterales (NDM-CRE) in hospitalized patients has increasingly been observed since 2018, leading in 2019 to the implementation of enhanced control measures successfully reducing transmission. We describe the NDM-CRE epidemiology during the COVID-19 pandemic in Tuscany. METHODS: Data on NDM-CRE patients hospitalized in five Tuscan hospitals were collected from January 2019 to December 2021. Weekly rates of NDM-CRE cases on hospital days in medical and critical-care wards were calculated. In March-December 2020, NDM-CRE rates were stratified by COVID-19 diagnosis. Multi-variate regression analysis was performed to assess outcomes' differences among two periods analysed and between COVID-19 populations. RESULTS: Since March 2020, an increase in NDM-CRE cases was observed, associated with COVID-19 admissions. COVID-19 patients differed significantly from non-COVID-19 ones by several variables, including patient features (age, Charlson index) and clinical history and outcomes (NDM-CRE infection/colonization, intensive care unit stay, length of stay, mortality). During the pandemic, we observed a higher rate of NDM-CRE cases per hospital day in both non-COVID-19 patients (273/100,000) and COVID-19 patients (370/100,00) when compared with pre-pandemic period cases (187/100,00). CONCLUSIONS: Our data suggest a resurgence in NDM-CRE spread among hospitalized patients in Tuscany during the COVID-19 pandemic, as well as a change in patients' case-mix. The observed increase in hospital transmission of NDM-CRE could be related to changes in infection prevention and control procedures, aimed mainly at COVID-19 management, leading to new challenges in hospital preparedness and crisis management planning.

A randomized controlled trial to examine the efficacy and safety of a new super-oxidized solution for the management of wide postsurgical lesions of the diabetic foot.

This randomized trial was done to test the effectiveness and safety of using a novel antiseptic solution (Dermacyn(R) Wound Care [DWC], Oculus Innovative Sciences, Petaluma, CA) in the management of the postoperative lesions on the infected diabetic foot. 40 patients with postsurgical lesions wider than 5 cm2 left open to heal by secondary intention were randomized into 2 groups. Group A was locally treated with DWC, whereas group B received povidone iodine as local medication, both in adjunct to systemic antibiotic therapy and surgical debridement if needed. Ischemia, renal failure, bilateral lesions, or immunodepression were considered as exclusion criteria. Patients were followed up weekly for 6 months. The primary endpoint was healing rate at 6 months, while secondary endpoints were healing time, time to achieve negative cultures, duration of antibiotic therapy, number of reinterventions, and adverse events. Healing rates at 6 months were significantly shorter in group A (90%) than in group B (55%; P < .01). The time taken for cultures to become negative and duration of antibiotic therapy were also significantly (P < .05) shorter in group A than in group B, whereas the number of reinterventions was significantly higher in group B (P < .05). No difference was noted in the adverse events except that for reinfections, which were more frequent in group B than in group A (P < .01). DWC is as safe as and more effective than standard local antiseptics in the management of wide postsurgical lesions in the infected diabetic foot.

Linezolid treatment for gram-positive infections: a retrospective comparison with teicoplanin.

In randomized studies linezolid, indicated for Gram-positive infections, was as effective as teicoplanin in critical ill patients or was superior to teicoplanin in skin infection, pneumonia and bacteremia. We performed a 2-year comparative, retrospective study of patients treated with linezolid or teicoplanin in a single hospital for the same indications. We collected information about the type of infection, the responsible pathogen, therapy administered before study drugs, antibiotic associated with the study drugs, length of hospital stay (LOS), adverse events and outcome of the infections. The aim of the study was to evaluate the efficacy of linezolid in this retrospective patients series. Overall we identified 169 patients treated with linezolid and 91 with teicoplanin. Response to therapy, (resolution or improvement of infection) was better in patients treated with linezolid compared to teicoplanin (83.9% versus 69.2%, p=0.002). Response to therapy by type of pathogen showed the superior efficacy of linezolid against Staphylococcus aureus (including MRSA) and enterococci; although not statistically significant because of the small number of patients enrolled, they were close to significance (p<0.056 for S. aureus, p<0.055 for MRSA, p<0.061 for enterococci). Overall LOS in linezolid-treated patients was 4.6 days (p<0.041) less. Empirical use of linezolid reduced lOS by 6 days (p<0.038), especially in VAP and bacteremia patients (p<0.05). Mortality due to infection was 9.8% in both groups, and adverse events were most frequently documented in linezolid-treated patients. Linezolid was clinically superior to teicoplanin in the treatment of Gram-positive infections.

Colistin in combination with rifampin and imipenem for treating a blaVIM-1 metallo-beta-lactamase-producing Enterobacter cloacae disseminated infection in a liver transplant patient.

A case of bla(VIM-1) producing E. cloacae disseminated infection in a patient submitted to orthotopic liver transplantation is described. Synergism between colistin, rifampin and imipenem was studied in vitro and this combination of three drugs was used to treat E. cloacae infection. The synergistic activity of this combination was demonstrated showing an increased activity of the serum bactericidal activity in comparison with the bactericidal activity of the serum taken during the previous therapy.

Colistin, meropenem and rifampin in a combination therapy for multi-drug-resistant Acinetobacter baumannii multifocal infection. A case report.

A 16 year-old girl underwent a multifocal (lungs, skin, soft tissues) infection due to multiresistant Acinetobacter baumannii after a car crash. To treat such a severe disease we used a combination therapy of colistin (2 millions Units twice/day), rifampicin (600 mg/day), meropenem (1 g 3 times a day) after a synergistic activity test was performed (checkerboard method on Mueller-Hinton broth and 5x10(5) cfu/mL inoculum). After 24 days, when a significant clinical improvement was gained, the 3-drugs combination therapy was replaced with i.v. levofloxacin 500 mg twice/day but, after 10 days of quinolones therapy, fever started again and the same multidrug resistant (MDR) A. baumannii was isolated from the skin grafts, central venous catheter tip and bronchial alveolar lavage. A combination therapy with colistin and meropenem was therefore started and definitive defervescence was obtained after 10 days. This therapy was continued for 70 days even if the patient was apyretic because A. baumannii was still present in the skin secretions. After 109 days of hospitalization in our intensive care unit, the patient was transferred to a rehabilitative unit. This case shows how useful is, in selected cases, rediscovering old antibiotic drugs, specially when they are adopted as a combination therapy, and highlights the importance of the clinical microbiological laboratory as it may help clinicians in choosing the best drugs combination.

Clinical and microbiological efficacy of colistin therapy in combination with rifampin and imipenem in multidrug-resistant Pseudomonas aeruginosa diabetic foot infection with osteomyelitis.

The evaluation of the safety and effectiveness of colistin in association with rifampin and imipenem in 1 diabetic patient with severe diabetic foot infection (DFI) due to multidrug-resistant (MDR) Pseudomonas aeruginosa, complicated by osteomyelitis, is presented in this "Case Report". The patient received colistin after other ineffective antimicrobial treatment when an MDR P aeruginosa strain was isolated by cultural examination, together with a multidisciplinary care approach including surgical debridement and adequate offloading. The efficacy of combination colistin plus rifampin plus imipenem was observed with a checkerboard method and bactericidal activity of the serum. The patient received colistin combination therapy for 6 weeks with cure of the infection and without renal toxicity. These data suggest that colistin, in combination with rifampin and imipenem, is safe and effective, in promoting healing in DFI due to MDR P aeruginosa and suggest the need for controlled clinical studies.

Management of cardiac device infections: A retrospective survey of a non-surgical approach combining antibiotic therapy with transvenous removal.

Pacemakers (PMs) and implantable cardioverter defibrillators (ICDs) have become life-saving therapeutic tools for patients with cardiac arrhythmia. Complications include thrombosis, embolism and infections at a highly variable rate. Surgical removal of the infected device has been perceived as the only way to guarantee a successful outcome and to reduce the high risk of mortality. Recently, a transvenous extraction method has been developed to remove infected intracardiac leads without sternotomy. This survey was designed to evaluate the outcome of an approach combining antibiotic therapy with non-surgical transvenous complete removal for the management of cardiac device infections (CDIs). We reviewed case-histories of 121 patients (105 with PM and 16 with ICD infections). The aim of our retrospective survey was to ascertain that a non-invasive transvenous complete removal of the infected devices is safe and effective when associated with appropriate antibiotic therapy starting 10 days before the procedure and extending to at least three weeks after. The infected devices were successfully removed in all patients with a non-surgical transvenous technique. The infections were most frequently caused by coagulase-negative staphylococci (70%), Staphylococcus aureus (14%), and Gram-negative rods (12%). Polymicrobial infections were documented in 19 patients and represent 16% of all device-related infections. The removal of the devices was done during antibiotic therapy, administered for a median of 26 days (range 23 to 45 days). Neither fatalities nor relapse of infections were recorded in the patient population during the one-year follow-up visits. According to our experience, CDIs can be treated with antibiotic therapy and non-surgical removal of the entire infected device, thus allowing a successful reimplantation. This procedure prevents recurrent infections and operative mortality.

Clinical and microbiological efficacy of colistin therapy alone or in combination as treatment for multidrug resistant Pseudomonas aeruginosa diabetic foot infections with or without osteomyelitis.

We retrospectively evaluated the safety and effectiveness of colistin alone or in combination with other antimicrobials in eight diabetic patients with severe diabetic foot infections due to multidrug resistant (MDR) Pseudomonas aeruginosa, complicated in 4 cases by osteomyelitis. All patients received colistin after other ineffective antimicrobial treatment, when MDR P. aeruginosa strains were isolated by cultural examination and together with a multidisciplinary care approach including revascularization, surgical debridement and adequate offloading. The mean duration of therapy was 72 +/- 52.9 days. Six out of 8 patients (75%) successfully benefited from colistin therapy, while 2 patients failed and/or experienced side effects that led to discontinuation of therapy. Serious adverse events (i.e. acute renal failure and pulmonary edema) were observed in 1 patient. Our data allow us to conclude that colistin, alone or in combination with other antimicrobials, is safe and effective when administered as part of a multidisciplinary approach, to promote healing of diabetic foot infection due to MDR P. aeruginosa.

Microbiological activity and clinical efficacy of a colistin and rifampin combination in multidrug-resistant Pseudomonas aeruginosa infections.

The aim of the study was to assess the microbiological activity and clinical efficacy of colistin and rifampin combination against multidrug-resistant (MDR) Pseudomonas aeruginosa infections. The antimicrobial activity of the colistin/rifampin combination was evaluated using the checkerboard and time-kill curve methods against different MDR P. aeruginosa strains. The combination of rifampin and colistin resulted fully (1 strain) or partially (5 strains) synergistic for 6/7 strains and minimum inhibitory concentrations (MICs) in combination were reduced to easily obtainable therapeutic levels. The time-kill curves showed that the combination was bactericidal against the strains tested. The clinical efficacy of the combination was tested in four patients with difficult-to treat infections (sepsis or pneumonia) caused by MDR P. aeruginosa. All infections were successfully treated. Our microbiological and clinical observations suggest that the addition of rifampin to colistin may result in a synergistic bactericidal combination that may be useful in patients with infections caused by MDR P. aeruginosa which are difficult to cure.

Low frequency of axial involvement in Caucasian pediatric patients with seronegative enthesopathy and arthropathy syndrome after 5 years of disease.

In order to establish how many children with seronegative spondyloarthropathy (SpA) starting with peripheral arthritis and/or enthesitis will develop ankylosing spondylitis (AS), 13 consecutive Caucasian pediatric patients, (11 with the seronegative enthesopathy and arthropathy (SEA) syndrome and 2 with isolated B27 associated peripheral arthritis or enthesitis at entry), were followed prospectively with no loss for more than 5 years. Sacroiliac joint plain films obtained at the last visit were mixed with those of 14 control subjects and read blindly. The course of SpA was self-limiting in 6 patients and recurrent in the other 7. Six patients had episodes of inflammatory cervical and/or lumbar pain during followup. However, none showed any limitation of spinal movement in the asymptomatic periods. Only one patient (9.1%) of 11 with the SEA syndrome showed bilateral sacroiliitis and met New York criteria for AS after 5 years of disease. Our results suggest that the proportion of Caucasian children with the SEA syndrome developing AS is much lower than the 75% found in a similar study on Mexican children. Lack of evaluation of all patients after 5 years, the reading of pelvic plain films without reducing observer error, and the male predominance in the Mexican study, probably in addition to ethnic or environmental factors, may account for differences.

Hearing and vestibular disturbances in Behçet's syndrome.

In order to evaluate the prevalence of audiovestibular disturbances in Behçet's syndrome, we submitted 20 consecutive patients and 20 control subjects to detailed audiologic and vestibular examination in the last 3 years. A sensorineural hearing loss was found in 12 patients, 2 of whom revealed sudden deafness. Two other patients with neuro-Behçet's syndrome showed a vestibular function deficit, and 3 others exhibited altered caloric stimulation test results. Two of these last patients also revealed a simultaneous bilateral auditory deficit. HLA typing showed the presence of the B51 antigen in 10 of the 14 patients with ear involvement, while only 3 of the 6 patients without ear involvement were HLA-B51-positive. Results suggest that audiovestibular involvement is common in Behçet's syndrome: sudden deafness may be the first sign of ear disturbance; vestibular lesions may represent an early sign of neuro-Behçet's syndrome; and the HLA-B51 antigen is associated with ear involvement. Otoneurologic study can reveal hidden brain stem lesions in Behçet's patients during flare-ups of the disease, even without obvious signs of neurologic deficits.

The triggering role of physical injury in the onset of peripheral arthritis in seronegative spondyloarthropathy.

Three more cases of B27-positive patients who developed peripheral arthritis immediately after trauma are reported. The first had an exacerbation of arthritis in the right hip after falling from her motor-bike. The second had arthritis of the distal interphalangeal (DIP) joint of the right forefinger after shutting his finger in the door of his car. The third had arthritis of the right sternoclavicular joint after a road-accident while fastening her safety belt.

Coexistence of ochronosis and ankylosing spondylitis.

We describe a 65-year-old woman with ochronosis and ankylosing spondylitis. The coexistence of these 2 diseases has not previously been described. Differential radiological features of these conditions, which share some resemblances from the clinical point of view, are highlighted.

Differential diagnosis between osteitis condensans ilii and sacroiliitis.

Sacroiliitis of seronegative spondyloarthropathy may sometimes show on pelvis plain films findings indistinguishable from those of osteitis condensans ilii. Computed tomography (CT) can differentiate earlier than plain radiography between the 2 conditions; furthermore, it should also be possible to make this differentiation clinically. The aim of our study was to verify whether the criteria recently proposed by the European Spondylarthropathy Study Group (EESG) for the classification of spondyloarthropathy are useful. CT scans through the synovial part of the sacroiliac joints of 7 consecutive patients meeting the ESSG criteria and showing typical findings of osteitis condensans ilii on plain films were mixed with those of 15 consecutive patients with osteitis condensans ilii not meeting the ESSG criteria. Scans were examined for joint space and surface abnormalities blindly and independently by 2 observers. Six patients in the spondyloarthropathy group and one in the osteiitis condensans ilii group showed clear erosions and/or joint space narrowing of less than 2 mm in at least one joint. The difference was statistically significant (p less than 0.001). Our results suggest that by using criteria valid for the whole group of seronegative spondyloarthropathies, it is possible to differentiate clinically between seronegative spondyloarthropathies with sacroiliitis mimicking osteitis condensans ilii and "true" osteitis condensans ilii.

Ankylosing spondylitis with exuberant sclerosis in the sacroiliac joints, symphysis pubis and spine.

We report the case of a man with ankylosing spondylitis involving the symphysis pubis and some intervertebral discs in addition to the sacroiliac joints. The bone adjacent to each inflammatory area showed an unusually exuberant sclerosis. In the early phases of evolution the appearance of sacroilitis was indistinguishable from that of osteitis condensans ilii.