Compassionate Use of Remdesivir in Children With Severe COVID-19.

OBJECTIVES: Remdesivir shortens time to recovery in adults with severe coronavirus disease 2019 (COVID-19), but its efficacy and safety in children are unknown. We describe outcomes in children with severe COVID-19 treated with remdesivir. METHODS: Seventy-seven hospitalized patients <18 years old with confirmed severe acute respiratory syndrome coronavirus 2 infection received remdesivir through a compassionate-use program between March 21 and April 22, 2020. The intended remdesivir treatment course was 10 days (200 mg on day 1 and 100 mg daily subsequently for children ≥40 kg and 5 mg/kg on day 1 and 2.5 mg/kg daily subsequently for children <40 kg, given intravenously). Clinical data through 28 days of follow-up were collected. RESULTS: Median age was 14 years (interquartile range 7-16, range <2 months to 17 years). Seventy-nine percent of patients had ≥1 comorbid condition. At baseline, 90% of children required supplemental oxygen and 51% required invasive ventilation. By day 28 of follow-up, 88% of patients had a decreased oxygen-support requirement, 83% recovered, and 73% were discharged. Among children requiring invasive ventilation at baseline, 90% were extubated, 80% recovered, and 67% were discharged. There were 4 deaths, of which 3 were attributed to COVID-19. Remdesivir was well tolerated, with a low incidence of serious adverse events (16%). Most adverse events were related to COVID-19 or comorbid conditions. Laboratory abnormalities, including elevations in transaminase levels, were common; 61% were grades 1 or 2. CONCLUSIONS: Among 77 children treated with remdesivir for severe COVID-19, most recovered and the rate of serious adverse events was low.

Mecillinam/clavulanate combination: a possible option for the treatment of community-acquired uncomplicated urinary tract infections caused by extended-spectrum ß-lactamase-producing Escherichia coli.

BACKGROUND: Extended-spectrum ß-lactamases (ESBLs) have emerged as an important mechanism of ß-lactam resistance among community uropathogens. We characterized the ESBLs of a collection of Escherichia coli isolates recovered from outpatients with urinary tract infection during nationwide surveillance conducted from 2005 to 2006 in Greece, and evaluated the in vitro activity of mecillinam and mecillinam/clavulanate against them. MATERIALS AND METHODS: ESBLs were characterized with PCR and sequencing. In vitro interactions were evaluated with agar dilution with and without clavulanate (4 mg/L) using an inoculum of 10(4) or 10(6) cfu/spot as well as with time-kill methodology. RESULTS: Among 48 ESBL producers, 47 (97.9%) were susceptible to mecillinam. CTX-M-type enzymes were produced by 87.2%, with CTX-M-3 being the most prevalent. SHV enzymes were found in 10.6%, VEB enzymes in 2.1%, TEM enzymes in 19.2% and OXA-type enzymes in 12.8%. Synergy with clavulanate was detected in 60.4% using the agar dilution method and in 43.8% using the time-kill methodology. An inoculum effect was detected in 64.6% of isolates, but this phenomenon was inverted and synergy was evidenced for 85.4% with clavulanate. When a high inoculum was used, 60.4% (29/48) were resistant to mecillinam, but 97.9% (47/48) were susceptible in the presence of clavulanate. CONCLUSIONS: CTX-M-type enzymes were the most prevalent among ESBL-producing E. coli uropathogens in Greece. Mecillinam may be useful in uncomplicated cystitis caused by ESBL producers with low MICs. The addition of the inhibitor could improve and extend the activity of mecillinam, even in the setting of infection with a high bacterial inoculum, and merits clinical evaluation.

Acute uncomplicated cystitis: from surveillance data to a rationale for empirical treatment.

The objectives of this study were to explore the epidemiological features and resistance rates in uropathogens isolated from cases of acute uncomplicated cystitis (AUC) in Greece, and subsequently to guide empirical treatment. Urine samples from outpatients aged >16 years were cultured and for each uropathogen isolated non-susceptibility to orally administered antimicrobial agents was defined. Demographic and clinical data were provided in questionnaire form. From January 2005 to March 2006 a total of 1936 non-duplicate positive urinary cultures were collected and 889 AUC cases were evaluated. Escherichia coli was the main aetiological agent (83%). In the AUC group, non-susceptibility rates for E. coli isolates were as follows: amoxicillin 25.8%; co-trimoxazole 19.2%; cefalothin 14.9%; nitrofurantoin 10.7%; amoxicillin/clavulanic acid 5.2%; nalidixic acid 6%; mecillinam 3.4%; ciprofloxacin 2.2%; cefuroxime 1.7%, and fosfomycin 1.6%. Amoxicillin and/or co-trimoxazole use in the previous 3 months was significantly associated with isolation of a co-trimoxazole-resistant E. coli isolate. The same applied for previous use of a fluoroquinolone agent and isolation of a ciprofloxacin-resistant E. coli isolate. In conclusion, increased co-trimoxazole non-susceptibility rates undermine its use as a first-line agent in empirical treatment, especially in cases of recent use of co-trimoxazole and/or amoxicillin. Fluoroquinolones display potent in vitro activity against community uropathogens, but prudent use is warranted for uncomplicated infections. Mecillinam and nitrofurantoin could serve as effective front-line agents in an effort to design fluoroquinolones-sparing regimens.

Idiopathic sclerosing encapsulating peritonitis (or abdominal cocoon).

BACKGROUND: Idiopathic sclerosing encapsulating peritonitis (or abdominal cocoon) is a rare cause of small bowel obstruction, especially in adult population. Diagnosis is usually incidental at laparotomy. We discuss one such rare case, outlining the fact that an intra-operative surprise diagnosis could have been facilitated by previous investigations. CASE PRESENTATION: A 56 year-old man presented in A&E department with small bowel ileus. He had a history of 6 similar episodes of small bowel obstruction in the past 4 years, which resolved with conservative treatment. Pre-operative work-up did not reveal any specific etiology. At laparotomy, a fibrous capsule was revealed, in which small bowel loops were encased, with the presence of interloop adhesions. A diagnosis of abdominal cocoon was established and extensive adhesiolysis was performed. The patient had an uneventful recovery and follow-up. CONCLUSION: Idiopathic sclerosing encapsulating peritonitis, although rare, may be the cause of a common surgical emergency such as small bowel ileus, especially in cases with attacks of non-strangulating obstruction in the same individual. A high index of clinical suspicion may be generated by the recurrent character of small bowel ileus combined with relevant imaging findings and lack of other plausible etiologies. Clinicians must rigorously pursue a preoperative diagnosis, as it may prevent a "surprise" upon laparotomy and result in proper management.

Septic arthritis due to Salmonella enteritidis associated with infliximab use.

A unique case of septic arthritis caused by Salmonella enteritidis in a patient receiving infliximab for rheumatoid arthritis is presented. Antimicrobial chemotherapy with surgical intervention was necessary for eradication of the infection. Physicians should be aware of rare manifestations of Salmonella infections associated with infliximab use, especially in endemic areas.