Penicillins, antipseudomonal

Key examples

• Piperacillin with tazobactam (e.g. Tazocin®)

 

Common indications

• Antipseudomonal penicillins are reserved for severe infections, particularly where there is a broad spectrum of potential pathogens (including Pseudomonas aeruginosa); antibiotic resistance is likely (e.g. hospital-acquired infection); or patients are immunocompromised (e.g. neutropenia). 
• Clinical infections treated with these drugs include:
  
  1. Lower respiratory tract infection.
  2. Urinary tract infection.
  3. Intra-abdominal sepsis.
  4. Skin and soft tissue infection.

 

Mechanisms of action

• Penicillins inhibit the enzymes responsible for cross-linking peptidoglycans in bacterial cell walls. This weakens cell walls, preventing them from maintaining an osmotic gradient. Uncontrolled entry of water into bacteria causes cell swelling, lysis and death.
• Penicillins contain a β-lactam ring, which is responsible for their antimicrobial activity. Side chains attached to the β-lactam ring can be modified to make semi-synthetic penicillins. For piperacillin, the side chain of broad-spectrum penicillins has been converted to a form of urea. This longer side chain may improve affinity to penicillin binding proteins, increasing the spectrum of antimicrobial activity to include Pseudomonas aeruginosa. Addition of the β-lactamase inhibitor tazobactam confers antimicrobial activity against β-lactamase-producing bacteria (e.g. Staphylococcus aureus, Gram-negative anaerobes).

 

Important adverse effects

• Gastrointestinal upset including nausea and diarrhoea is common. Less frequently, antibiotic-associated colitis occurs when broad-spectrum antibiotics kill normal gastrointestinal flora, allowing overgrowth of toxin-producing Clostridium difficile. This is debilitating and can be complicated by colonic perforation and/or death. Delayed or immediate hypersensitivity may occur (see Penicillins).

 

Warnings

• Antipseudomonal penicillins should be used with caution in people at risk of C. difficile infection, particularly those in hospital and the elderly. The main contraindication is a history of penicillin allergy. Note that allergy to one type of penicillin implies allergy to all types as it is due to a reaction to the basic penicillin structure. The dose of antipseudomonal penicillins should be reduced in patients with moderate/severe renal impairment.

Important interactions

• Penicillins reduce renal excretion of methotrexate, increasing the risk of toxicity. 
• Antipseudomonal penicillins can enhance the anticoagulant effect of warfarin by killing normal gastrointestinal flora that synthesise vitamin K.