2018 update! Just as relevant.

Upside – Ceftriaxone and cefotaxime (third generation cephalosporins-TGC) are amongst the most important agents for directed therapy of infections due to Gram negative organisms that are resistant to ampicillin or cephazolin (a first generation cephalosporin),  including Klebsiella pneumoniae .  They penetrate the CSF well, making them important agents for treatment of  meningitis due to Streptococcus pneumoniae and other susceptible pathogens.

Downside – third generation cephalosporins are  amongst the most misused and overused agents and as a result have strongly promoted the emergence and selection of resistant pathogens such as MRSA, VRE , extended-spectrum betalactamase (ESBL) producing coliforms, Enterobacter and related species (ampC cephalosporinase producers) and Clostridium difficile infection.

The bottom line- 

• Hunter New England target is to maintain usage of third generation cephalosporins below 20 defined-daily doses per 1,000 patient-days
• Implement guidelines that remove third generation cephalosporins from most empiric indications- see Australian Therapeutic Guidelines: Antibiotic for alternative choices – in particular, Hunter New England relies on IV benzylpenicillin or oral amoxycillin in its community-acquired pneumonia guideline
• Avoid use of third generation cephalosporins for surgical prophylaxis
• Reductions in hospital usage are demonstrated to reduce prevalence of ceftriaxone-resistant infections and C. difficile  (see Scottish reference below and graphic)

Potential interventions to reduce use in hospital settings – 

• Establish a program to minimise duration of parenteral TGC therapy and promote correct oral switch options
• Establish local antibiotic guidelines that restrict indications for empiric use of TGC and specify agreed directed use indications
• Establish correct laboratory antimicrobial susceptibility testing and reporting practice. Consider routine report comment to advise clinicians of the local restrictions that are in place.
• Monitor TGC prescriptions actively and provide feedback to prescribers where the prescription does not meet established criteria for use
• Perform drug usage evaluation studies to assess management of patients with defined clinical syndromes such as pneumonia. Assess compliance of therapy and feedback results to prescribers
• Monitor susceptibility patterns and feed these results back to prescribers

Clinical Situations where third generation cephalosporins are used but not always required –

• Pneumonia and respiratory tract infection;
  • Considerable data demonstrate effective lung penetration of aminoglycosides into the alveolar line fluid making them effective empiric agents in situations where Gram negative pneumonia may be possible/probable.  
  • Presence of pneumococcal pneumonia due to S. pneumoniae with a raised penicillin MIC (reduced susceptibility) is not a justification for TGC use- benzylpenicillin remains effective at MICs <=4 mg/L (dose increases may be prudent).  
  • Benzylpenicillin and amoxycillin retain activity against betalactamase negative Haemophilus influenzae. Gentamicin is also active.
• Urinary tract infection; Avoid the use of TGC as first line empiric treatment unless there are contraindications to gentamicin. Use ampicillin + gentamicin as per Australian Therapeutic Guidelines: Antibiotic, with maximum of three daily doses of gentamicin (most usually gentamicin is ceased after one dose). Therapy can then usually be directed on the basis of urine or blood results- to cephazolin, trimethoprim or ampicillin/amoxycillin for susceptible isolates.
• Biliary tract sepsis/cholecystitis; biliary penetration of antibiotics is not the issue- no antibiotic penetrates an obstructed biliary tract for at least 1 day following relief of obstruction. The most important issues are a) relief of biliary obstruction and b) treatment of bacteraemia. Ampicillin and gentamicin represent a proven empiric combination with adequate spectrum (see Australian Therapeutic Guidelines: Antibiotic).
• Meningococcal sepsis and meningitis; when infection proven, always switch the non-allergic patient to benzylpenicillin and limit duration of treatment to 3-5 days total.

References

1. Recent Scottish stories – sustained changes to the 4C antibiotic use in hospitals and community lead to significant reductions in MRSA and C. difficile infections.
   • MRSA – Lancet Infect Dis 2015; 15: 1438–49  + editorial
   • C. difficile – Lancet Infect Dis 2017; 17: 194–206 + editorial
2. Collins, T, Gerding DN.  Aminoglycosides versus Betalactams in Gram negative pneumonia.  Seminars in Respiratory Tract Infections 1991:6:136-146.
3. Craig,W. Andes,D.  Aminoglycosides are useful for severe respiratory tract infections. Seminars in Respiratory Tract Infections 1997:12:271-77.