ClinicalDesk Blog

Carbapenem-resistant Enterobacterales (CRE) represent one of the most serious antimicrobial resistance threats facing UK hospitals today. Recent PHE surveillance data shows a year-on-year increase in CRE isolates, particularly in ICU and haematology settings.

What is CRE?

CRE refers to Enterobacterales (including Klebsiella pneumoniae, E. coli, and Enterobacter spp.) that have developed resistance to carbapenem antibiotics — our last-line agents for serious Gram-negative infections.

The main resistance mechanisms include:

• KPC (Klebsiella pneumoniae carbapenemase) — most common in the UK
• NDM (New Delhi metallo-beta-lactamase) — often imported, increasingly prevalent
• OXA-48 — widespread in Southern Europe and Middle East

Clinical Implications

Treatment options are severely limited and include:

• Ceftazidime-avibactam (for KPC and OXA-48) — requires ID authorisation
• Aztreonam-avibactam (for NDM producers) — specialist use only
• Colistin — significant nephrotoxicity, use as last resort

Your Role as a Prescriber

Before starting a carbapenem, ask: could this be treated with piperacillin-tazobactam? Could we await sensitivities before escalating? Is microbiology input available?

Intravenous antibiotic therapy is frequently continued for longer than necessary in UK hospitals. Studies suggest that up to 40% of IV antibiotic days could be safely converted to oral therapy earlier than they are.

The CAPS Criteria

A patient is eligible for IV to oral switch when all four CAPS criteria are met:

• C — Can swallow and absorb oral medication
• A — Apyrexial for at least 24 hours
• P — Patient is clinically improving (CRP trending down, WBC normalising)
• S — Suitable oral agent is available with adequate bioavailability

Why Does Early Switching Matter?

The benefits of early switching include:

• Reduced central line-associated bloodstream infection (CLABSI) risk
• Shorter inpatient admission (oral antibiotics = patient can go home)
• Lower cost — oral antibiotics are significantly cheaper
• Reduced nursing time and administration burden
• Improved patient experience and mobility

High Bioavailability Agents — Safe to Switch

The following have oral bioavailability >80% and are safe to switch in most circumstances: metronidazole, fluconazole, co-trimoxazole, doxycycline, clindamycin, levofloxacin, linezolid.

Make IV to oral switch review a daily ward round agenda item. If you're not asking "can we switch this today?", you're probably leaving patients on IV antibiotics longer than necessary.

NICE NG191 updated the guidance on community-acquired pneumonia (CAP) management for adults and children. The key changes moved away from prolonged antibiotic courses and emphasised severity-guided prescribing.

The Key Changes

• 5-day course is now recommended for low-moderate severity CAP — down from 7 days
• CURB-65 remains the recommended severity scoring tool for adults
• Emphasises IV to oral switch early when CAPS criteria are met
• Atypical cover (clarithromycin) recommended for moderate-severe CAP

Practical Prescribing Summary

What Hasn't Changed

Legionella and pneumococcal urinary antigen tests remain recommended for moderate-severe CAP. Blood cultures should be taken before antibiotics in hospitalised patients without delaying treatment beyond 45 minutes.

Vancomycin is one of the most commonly used antibiotics for serious Gram-positive infections in UK hospitals, yet therapeutic drug monitoring (TDM) practices vary significantly between trusts.

The Old Approach: Trough Monitoring

Traditionally, vancomycin TDM focused on pre-dose (trough) levels, targeting 15–20 mg/L for serious infections. However, evidence has shown that targeting high troughs alone is associated with nephrotoxicity without necessarily improving efficacy.

The New Standard: AUC/MIC Monitoring

International guidelines now recommend targeting an AUC/MIC ratio of 400–600 mg·h/L as the pharmacodynamic target for vancomycin. This approach:

• Reduces nephrotoxicity by avoiding unnecessarily high concentrations
• Maintains efficacy against susceptible organisms (MIC ≤1 mg/L)
• Requires both trough and peak levels (or Bayesian software) to calculate

Practical Points

• Load with 25–30 mg/kg for serious infections (MRSA bacteraemia, endocarditis)
• Take first TDM levels at 48h (or after 3rd dose for twice-daily dosing)
• Monitor renal function daily — dose-adjust if CrCl changes significantly
• Avoid concomitant nephrotoxins (gentamicin, NSAIDs, contrast) where possible

A confirmed national shortage of IV co-amoxiclav (Augmentin) is affecting hospitals across England. This affects a broad range of indications including surgical prophylaxis, biliary infections, aspiration pneumonia, and polymicrobial infections.

Recommended Alternatives by Indication

• Biliary sepsis / cholangitis: Piperacillin-tazobactam 4.5g TDS IV ± Metronidazole
• Aspiration pneumonia: Amoxicillin 1g TDS IV + Metronidazole 500mg TDS IV
• Surgical prophylaxis: Cefuroxime 1.5g IV + Metronidazole 500mg IV (single dose)
• UTI (severe): Ceftriaxone 1–2g OD IV — check local sensitivities
• Skin and soft tissue: Flucloxacillin + Metronidazole if anaerobic cover required

Oral Co-amoxiclav

Oral co-amoxiclav (625mg tablets) is currently unaffected by the shortage and can be used where a suitable oral switch is appropriate and CAPS criteria are met.