Synopsis
Distinguish resistant Enterobacterales carriage from infection, obtain high-quality cultures before treatment, map the resistance mechanism and infection site, choose active narrow therapy with microbiology ownership, and prevent healthcare transmission.
- Extended-spectrum beta-lactamases hydrolyse most penicillins and third-generation cephalosporins but usually leave carbapenems active; co-resistance to quinolones and co-trimoxazole is common.
- Carbapenemase-producing Enterobacterales carry enzymes such as KPC, OXA-48-like, NDM, VIM or IMP; the enzyme class predicts which newer beta-lactam combination can work.
- Colonisation of the bowel, urine around a catheter or a chronic wound does not itself require antibiotics; treat an attributable clinical infection, not the resistance result.
- Obtain blood and high-quality source cultures before antimicrobials when safe and retrieve every previous isolate, susceptibility, carbapenemase result and overseas healthcare exposure.
- For severe ESBL bloodstream or non-urinary infection, meropenem 1 g intravenously every eight hours is a common first-line regimen pending site, MIC and renal review.
- For susceptible uncomplicated lower UTI, nitrofurantoin or another narrow oral agent can spare carbapenems; never extrapolate that susceptibility to pyelonephritis or sepsis.
- NICE restricts ceftazidime-avibactam to severe resistant Gram-negative infection with specialist advice, supported susceptibility and no suitable alternative; it is particularly useful for OXA-48-like and selected KPC producers.
- CPE control requires immediate IPC notification, risk-based single-room or cohort care, contact precautions, flags, transfer communication and contact screening; routine antibiotic decolonisation is not recommended.
Key red flags
Shock, rising lactate, altered consciousness, oliguria or respiratory failure requires immediate broad active intravenous therapy and source control.
Previous carbapenemase-producing Enterobacterales, overseas hospitalisation, transfer from an outbreak facility or a known colonised household contact should trigger urgent IPC and empirical-treatment review.
Pyelonephritis, obstruction, renal abscess or bacteraemia must not be treated with nitrofurantoin or oral fosfomycin because tissue and serum exposure are inadequate.
Persistent bacteraemia despite an apparently susceptible drug raises inadequate exposure, undrained source, infected device, heteroresistance or emergence of resistance.
NDM, VIM or IMP metallo-beta-lactamase is not inhibited by avibactam alone; mechanism-specific combination or cefiderocol decisions require specialist laboratory evidence.
Pregnancy, renal failure, augmented renal clearance, epilepsy, valproate therapy and severe beta-lactam allergy can materially alter carbapenem or novel-agent prescribing.
Dysuria and frequency suggest lower UTI, while fever, loin pain, vomiting or sepsis indicates upper-tract or bloodstream involvement requiring systemic exposure.
Investigation priorities
Identify the current pathogen and susceptibility from blood, urine, deep tissue, bile, drainage or another true infection focus.
Management branches
A patient with ESBL or CPE risk develops local symptoms, fever, sepsis or a new positive culture.
- Perform ABCDE and obtain blood plus high-quality source cultures before antimicrobials if collection is immediate; do not delay resuscitation or an active first dose in shock.
- Retrieve previous species, MICs and carbapenemase results, overseas or outbreak healthcare and recent antibiotics and devices.
- Distinguish asymptomatic colonisation, asymptomatic bacteriuria and catheter growth from a clinical infection using symptoms, physiology and specimen quality.
- Alert microbiology for empirical selection and IPC for CPE risk, isolation, screening and transfer communication.