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Background Carbapenemase-producing Escherichia coli are increasing worldwide. In recent years, an increase in OXA-244-producing E. coli isolates has been seen in the national surveillance of carbapenemase-producing organisms in Denmark. Aim Molecular characterisation and epidemiological investigation of OXA-244-producing E. coli isolates from January 2016 to August 2019. Methods For the epidemiological investigation, data from the Danish National Patient Registry and the Danish register of civil registration were used together with data from phone interviews with patients. Isolates were characterised by analysing whole genome sequences for resistance genes, MLST and core genome MLST (cgMLST). Results In total, 24 OXA-244-producing E. coli isolates were obtained from 23 patients. Among the 23 patients, 13 reported travelling before detection of the E. coli isolates, with seven having visited countries in Northern Africa. Fifteen isolates also carried an extended-spectrum beta-lactamase gene and one had a plasmid-encoded AmpC gene. The most common detected sequence type (ST) was ST38, followed by ST69, ST167, ST10, ST361 and ST3268. Three clonal clusters were detected by cgMLST, but none of these clusters seemed to reflect nosocomial transmission in Denmark. Conclusion Import of OXA-244 E. coli isolates from travelling abroad seems likely for the majority of cases. Community sources were also possible, as many of the patients had no history of hospitalisation and many of the E. coli isolates belonged to STs that are present in the community. It was not possible to point at a single country or a community source as risk factor for acquiring OXA-244-producing E. coli.

We studied the patients admitted to the ICU at a Danish university hospital during 1 year with respect to nosocomial pneumonia (NP). Among 242 patients, who stayed more than 48 h, 23 (10%) developed NP. Patients with NP had significantly higher mortality (43% vs. 19%, p less than 0.05), longer median stay (276 h vs. 99 h, p less than 0.05) and a longer median intubation period (256 h vs. 74 h, p less than 0.05). In the NP group surgical patients were overrepresented as compared to medical patients (74% vs. 45%, p less than 0.05). Thoracotomy, treatment with H-2 blockers and immunosuppression represented significant risk factors. Considering the etiology, Enterobacteriaceae and Pseudomonas aeruginosa constituted 43% of the cases in strong contrast to the low frequency of these pathogens in community-acquired pneumonia. NP in the ICU patient is a resource consuming disease associated with a high mortality (43%), which is related to the frequent severe underlying diseases of these patients.

The intracellular activity of a number of drugs used alone and in combinations against Staphylococcus aureus was investigated using an experimental design which imitates the clinical situation and differs from other published methods. Staphylococci were phagocytosed by human polymorphonuclear leukocytes and, after differential centrifugation and washing, the granulocytes were incubated in 90% pooled human serum with clinically relevant drug concentrations. When exposed to antibiotics, more than 40 50% of the bacteria were located intracellularly. Fusidic acid (100 mg/1), erythromycin (20 mg/1), and clindamycin (20 mg/1) all had a bacteriostatic effect during the first 6 h of incubation, whereas rifampicin (1 and 5 mg/1), vancomycin (5 and 20 mg/1), and ciprofloxacin (2 mg/1) all acted bactericidally with decreases in viable counts between 1.3–1.9 log10. The greatest bactericidal effect was achieved with tobramycin (10 mg/1), which produced more than a 4 log10 decrease in viable counts at 6 h. Combinations of fusidic acid with other antibiotics all resulted in killing kinetics different from those achieved with the drugs used individually. The bactericidal effect of ciprofloxacin and dicloxacillin during the first 6 h was abolished when these drugs were combined with fusidic acid. However, at 24 h no significant difference was found between the effect of dicloxacillin alone versus the combination dicloxacillin and fusidic acid. The combination of fusidic acid and rifampicin resulted in a killing identical to that achieved with rifampicin used alone during the first 6 h, but at 24 h the killing by the combination was significantly greater. The bactericidal effect of the combination dicloxacillin (20 mg/1) and tobramycin (10 mg/1) equalled that obtained with tobramycin (10 mg/1) used alone. Rifampicin (5 mg/1) antagonized the bactericidal effect of ciprofloxacin (2 mg/1) during the first 6 h of incubation but at 24 h the combination acted synergistically. The results obtained are partly in agreement and partly in conflict with previous results.