Report of terbinafine resistant Trichophyton spp. in Italy: Clinical presentations, molecular identification, antifungal susceptibility testing and mutations in the squalene epoxidase gene.

BACKGROUND: Numerous reports of resistance to terbinafine in Trichophyton spp. from all over the world are arousing justified attention and concern. Point mutations in the gene that encodes the squalene epoxidase (SQLE) enzyme are responsible for these therapeutic resistances. OBJECTIVES: Primary objective of the study was to describe first isolates of Trichophyton spp. resistant to terbinafine among the patients treated between September 2019 and June 2022 at the Dermatology Units of Ospedale Maggiore Policlinico and San Bortolo Hospital. Secondary objective was to study the resistance mechanism. METHODS: Patients with confirmed Trichophyton spp. infection has been treated with systemic and topical terbinafine. Patients were then re-evaluated 12 weeks after the therapy. Patients with incomplete or absent response to terbinafine underwent a new skin scraping for direct mycological examination, new identification of dermatophyte species from culture and MALDI-TOF, molecular species identification, antifungal susceptibility testing and molecular analysis of SQLE gene. RESULTS: We identified five patients without clinical response to treatment with terbinafine. The DNA sequencing of the ITS region identified one Trichophyton rubrum and four Trichophyton indotineae. The T. rubrum strain showed minimum inhibitory concentration (MIC) (90% growth inhibition) of 4 mg/L for terbinafine. The four T. indotineae strains showed a MICs range of 0.25-4 mg/L for terbinafine. The analysis of the SQLE gene in the T. rubrum strain showed a nucleotide substitution generating a missense mutation (L393F). The SQLE gene sequencing in the T. indotineae strains showed a nucleotide substitution generating a missense mutation (F397L) in two strains, a nucleotide substitution L393S in one strain and a nucleotide substitution F415C in another strain. CONCLUSIONS: We report the first cases of terbinafine-resistant Trichophyton isolates in the Italian population. Solid antifungal management programs will be needed to promote more responsible use of antimycotics and preserve their therapeutic efficacy to control antifungal resistance.

Parenteral antibiotics and selective intestinal decontamination do not prevent enteric bacterial overgrowth or translocation observed in a swine model of small bowel transplantation.

Alterations in the luminal microflora and increased intestinal translocation have been reported to occur following experimental and clinical small bowel transplantation (SBT). Selective intestinal decontamination (SID) has been used to prevent luminal overgrowth and bacterial translocation. Despite the wide use of SID in clinical SBT, there are no data supporting its usefulness in this situation. Thus, the aim of this investigation was to examine the effects of cyclosporine A (CsA) and SID upon bacterial overgrowth and translocation in a swine model of SBT. Nineteen Large White female pigs weighing 30 +/- 2 kg underwent a total orthotopic SBT and were randomly allocated to one of the following experimental groups as follows: Group 1 (No. 8) CSA 25 mg/kg body weight (b.w.)/day administered subcutaneously and Cefazolin 2 g/day im. Group 2 (No. 6) received the identical immunosuppression but the Cefazolin 2 g/day im was discontinued on the 5th Postoperative Day (pod) and switched to a SID regimen consisting of Vancomycin, 1 g, Nystatin, 500,000 IU, Colistin, 1,500,000 IU, and Tobramycin, 100 mg, given through a gastrostomy tube. Group 3 (No. 5) received no immunosuppression but antibiotic consisting of Cefazolin 2 g im/day. Group 4 (No. 7) underwent a small bowel autotransplantation. Group 4 received SID as in group 2 but no immunosuppression was given. Finally, 17 normal animals were sham-operated and were used as normal controls (N group). The animals in groups 1, 2, and 4 were sacrificed on the 29th pod. Those in group 3 were sacrificed on the 7th pod.(ABSTRACT TRUNCATED AT 250 WORDS)

Luminal bacterial overgrowth and intestinal translocation in pigs given either cyclosporin A or 15-deoxyspergualin after small bowel transplantation.

OBJECTIVE: To examine the effects of two immunosuppressant regimens on composition of the bowel flora and rate of translocation after transplantation of the small bowel in pigs. DESIGN: Randomised controlled study. SETTING: University hospital, Italy. MATERIAL: 35 female Large White pigs. INTERVENTIONS: 9 Animals were not operated on (normal controls). 19 Animals underwent total orthotopic small bowel allotransplantation and were then randomised to receive: group A (n = 8) cyclosporin A 25 mg/kg subcutaneously and cephazolin 2 g intramuscularly daily; group B (n = 6) 15-deoxyspergualin (15-dos) 3 mg/kg for 7 days then 1.5 mg/kg, cephazolin 2 g intramuscularly daily for 4 days then selective intestinal decontamination with colistin 1.5 million U, tobramycin 100 mg, vancomycin 1 g, and nystatin 500,000 U daily; and group C (n = 5) cephazolin 2 g intramuscularly daily for 8 days. A further group (D, n = 7) underwent orthotopic autotransplantation and received the same antibiotic and selective decontamination regimens as group B. Animals in group C were killed on day 8, and the rest on day 29. MAIN OUTCOME MEASURES: Signs of rejection, graft versus host disease, luminal overgrowth, and evidence of translocation to mesenteric lymph nodes. RESULTS: All animals in group C, and 2 in group B, showed signs of acute rejection. There was a significant overgrowth of both aerobic and anaerobic bacteria in all 3 groups after allotransplantation compared with normal controls. Bacterial translocation was similar in autografted and allotransplanted animals. Mesenteric lymph nodes were colonised in 4/9 controls, 7/8 in group A, 4/4 in group B, 5/5 in group C, and 7/7 in group D. CONCLUSION: Neither cyclosporin A nor 15-dos prevented luminal overgrowth or bacterial translocation to mesenteric nodes up to one month after operation. The rate of translocation was similar in autotransplantation and allotransplantation, suggesting that non-immunological factors (for example, denervation and interruption of lymphatics) may have a role in these alterations.

Infections in the surgical setting: epidemiology and effect of treatment with cefotaxime in a multicenter trial including 3,032 patients.

Hospital-acquired infections still represent a serious threat to the surgical patient. A nationwide survey of 259 Italian surgical wards involving 11,343 patients was conducted in October 1988. Hospital-acquired infections were recorded in 565 (5%) patients: the microorganisms most commonly involved were gram-negative rods (60% of all isolates), 41% of the infected patients presented one or more intrinsic predisposing factor, and 65% had undergone some invasive procedure. The studied group represented 23% of all surgical patients in the country on the days of the survey. Following the epidemiologic survey, an open multicenter study was conducted in the same wards to evaluate the efficacy and tolerability of cefotaxime (1 g, 2 or 3 times per day) in the treatment of nosocomial surgical infections. Among 3,032 evaluable patients, 1,295 intra-abdominal, 610 wound and soft tissue, 554 urinary, and 367 respiratory infections were observed. Treatment was judged to be clinically effective in 94% of patients, and side effects, mostly involving the gastrointestinal tract, were observed in 1.4% of patients; but interruption of the treatment was required only in 19 patients (0.6%). This study confirms that cefotaxime, after over a decade of use, retains high efficacy in the treatment for nosocomial infections and induces a low rate of side effects.