Objectives Third-generation cephalosporin-resistant Escherichia coli from community-acquired urinary tract infections are increasingly reported worldwide. We sought to determine and characterize the mechanisms of cefotaxime resistance employed by urinary E. coli obtained from primary care, over 12 months, in Bristol and surrounding counties in South-West England. Methods Cefalexin-resistant E. coli isolates were identified from GP-referred urine samples using disc susceptibility testing. Cefotaxime resistance was determined by subsequent plating onto MIC breakpoint plates. β-Lactamase genes were detected by PCR. WGS was performed on 225 isolates and analyses were performed using the Center for Genomic Epidemiology platform. Patient information provided by the referring general practices was reviewed. Results Cefalexin-resistant E. coli (n=900) isolates were obtained from urines from 146 general practices. Following deduplication by patient approximately 69% (576/836) of isolates were cefotaxime resistant. WGS of 225 isolates identified that the most common cefotaxime-resistance mechanism was blaCTX-M carriage (185/225), followed by plasmid-mediated AmpCs (pAmpCs) (17/225), AmpC hyperproduction (13/225), ESBL blaSHV variants (6/225) or a combination of both blaCTX-M and pAmpC (4/225). Forty-four STs were identified, with ST131 representing 101/225 isolates, within which clade C2 was dominant (54/101). Ciprofloxacin resistance was observed in 128/225 (56.9%) of sequenced isolates, predominantly associated with fluoroquinolone-resistant clones ST131 and ST1193. Conclusions Most cefalexin-resistant E. coli isolates were cefotaxime resistant, predominantly caused by blaCTX-M carriage. The correlation between cefotaxime resistance and ciprofloxacin resistance was largely attributable to the high-risk pandemic clones ST131 and ST1193. Localized epidemiological data provide greater resolution than regional data and can be valuable for informing treatment choices in the primary care setting.

Xanthogranulomatous pyelonephritis (XGP) is a rare histological subset of pyelonephritis characterized by being a chronic destructive granulomatous inflammation of the renal parenchyma. XGP is classified according to the extent of disease into two entities: within the renal cortex (focal or segmental XGP) or diffuse spread with pelvic communication (diffuse XGP). Although rare, XGP can have fatal complications including perinephric, psoas abscess, nephro-cutaneous fistula and reno-colic fistula. Only few studies have reported XGP complicated with psaos abcess and reno-colic fistula. Our aim is to add to the literature and share our experience with a case of extensive XGP eroding into the psoas muscle and ascending colon leading to severe sepsis that was successfully managed. We report a 56-year-old woman who was found to have XGP complicated by psoas abscess and reno-colic fistula managed by antibiotics, nephrostomy, and subsequent nephrectomy and partial colectomy.

A 61-year-old man was admitted with a history of right upper quadrant and left iliac fossa pain and raised inflammatory markers. Initial investigations, including contrast-enhanced CT scan of the abdomen and pelvis, were reported as normal. Following readmission 2 months later with thoracolumbar back pain and recurrent fevers, an MRI showed T11/12 discitis and an adjacent mycotic aneurysm of the aorta. CT angiogram confirmed an 8 cm mycotic aneurysm. A second, more distal aneurysm was found located at the left common femoral artery. The aortic aneurysm was treated by antegrade stenting. The left common femoral artery aneurysm was excised. The patient was also treated with antibiotics. He made a good recovery and was well 8 months later apart from mild residual thoracolumbar spinal pain. To date, he has been followed up for 1 year and remains asymptomatic.

Meropenem is a clinically important antibacterial reserved for treatment of multi-resistant infections. In meropenem-resistant bacteria of the family Enterobacteriales, NDM-1 is considerably more common than IMP-1, despite both metallo-β-lactamases (MBLs) hydrolysing meropenem with almost identical kinetics. We show that blaNDM-1 consistently confers meropenem resistance in wild-type Enterobacteriales, but blaIMP-1 does not. The reason is higher blaNDM-1 expression because of its stronger promoter. However, the cost of meropenem resistance is reduced fitness of blaNDM-1 positive Enterobacteriales because of amino acid starvation. In parallel, from a clinical case, we identified multiple Enterobacter spp. isolates carrying a plasmid-encoded blaNDM-1 having a modified promoter region. This modification lowered MBL production to a level associated with zero fitness cost but, consequently, the isolates were not meropenem resistant. However, we identified a Klebsiella pneumoniae isolate from this same clinical case carrying the same blaNDM-1 plasmid. This isolate was meropenem resistant despite low-level NDM-1 production because of a ramR mutation, reducing envelope permeability. Overall, therefore, we show how the resistance/fitness trade-off for MBL carriage can be resolved. The result is sporadic emergence of meropenem resistance in a clinical setting.

Pyogenic myositis is uncommon. It normally affects the large muscle groups in the lower limb or trunk and the most common causative organism is Staphylococcus aureus. We present a case of an immunocompetent man who, unusually, had a recurring form of the disease in subscapularis and teres minor. The causative organism was also highly unusual (Fusobacterium).