In vitro activity of new combinations of ß-lactam and ß-lactamase inhibitors against the Mycobacterium tuberculosis complex.

As meropenem-clavulanic acid is recommended for the treatment of drug-resistant tuberculosis, the repurposing of new carbapenem combinations may provide new treatment options, including oral alternatives. Therefore, we studied the in vitro activities of meropenem-vaborbactam, meropenem-clavulanic acid, and tebipenem-clavulanic acid. One hundred nine Mycobacterium tuberculosis complex (MTBC) clinical isolates were tested, of which 69 were pan-susceptible and the remaining pyrazinamide- or multidrug-resistant. Broth microdilution MICs were determined using the EUCAST reference method. Meropenem and tebipenem were tested individually and in combination with vaborbactam 8 mg/L and clavulanic-acid 2 and 4 mg/L, respectively. Whole-genome sequencing was performed to explore resistance mechanisms. Clavulanic acid lowered the modal tebipenem MIC approximately 16-fold (from 16 to 1 mg/L). The modal meropenem MIC was reduced twofold by vaborbactam compared with an approximately eightfold decrease by clavulanic acid. The only previously described high-confidence carbapenem resistance mutation, crfA T62A, was shared by a subgroup of lineage 4.3.4.1 isolates and did not correlate with elevated MICs. The presence of a ß-lactamase inhibitor reduced the MTBC MICs of tebipenem and meropenem. The resulting MIC distribution was lowest for the orally available drugs tebipenem-clavulanic acid. Whether this in vitro activity translates to similar or greater clinical efficacy of tebipenem-clavulanic acid compared with the currently WHO-endorsed meropenem-clavulanic acid requires clinical studies. IMPORTANCE Repurposing of already approved antibiotics, such as ß-lactams in combination with ß-lactamase inhibitors, may provide new treatment alternatives for drug-resistant tuberculosis. Meropenem-clavulanic acid was more active in vitro compared to meropenem-vaborbactam. Notably, tebipenem-clavulanic acid showed even better activity, raising the potential of an all-oral treatment option. Clinical data are needed to investigate whether the better in vitro activity of tebipenem-clavulanic acid correlates with greater clinical efficacy compared with the currently WHO-endorsed meropenem-clavulanic acid.

[First case of nephropathia epidemica in southern Sweden]. / Första fallet av skånsk sorkfeber - Ytterst sällsynt söder om Mälardalen ­ men nu tycks Puumalavirus spridas till nya områden i Sverige.

Nephropathia epidemica (NE) is the European version of hemorrhagic fever with renal syndrome. NE is caused by the Puumala type of Hantavirus with the bank vole (Clethrionomys glareolus) as the natural reservoir. Endemic regions include northern Sweden with an incidence of 53 to 569 cases per year, depending on the cyclic variation of rodent populations. In southern Sweden, south of the Mälardalen region, no cases of NE have been described without a historical account of travel to endemic areas in the weeks beforehand. This case report describes the course of disease of a patient diagnosed with NE, who had only stayed in the southernmost region of Sweden: Skåne. This may indicate the spread of NE to more southern regions of Sweden. NE should consequently be considered as a differential diagnosis at emergency and infectious disease departments throughout Sweden.