What are the recent treatment guidelines for a patient with a multi-drug resistant (MDR) Klebsiella infection?

Treatment of Multidrug-Resistant Klebsiella Infections

For carbapenem-resistant Klebsiella pneumoniae (CRKP) infections, ceftazidime-avibactam is the preferred first-line agent, particularly for severe infections including sepsis and bacteremia. 1

Treatment Algorithm by Infection Severity and Resistance Pattern

For Carbapenemase-Producing Klebsiella pneumoniae

Severe infections (sepsis, bacteremia, pneumonia):

• First-line: Ceftazidime-avibactam 2.5 g IV every 8 hours 1, 2

  • This agent demonstrates superior clinical cure rates compared to polymyxin-based regimens 3
  • Clinical cure rates of 83-86% documented in patients with ceftazidime-resistant isolates 2

• For metallo-beta-lactamase (NDM, VIM) producers resistant to ceftazidime-avibactam:

  • Aztreonam plus ceftazidime-avibactam combination therapy 3, 4
  • This combination overcomes metallo-beta-lactamase resistance mechanisms 4

• Alternative regimen when newer agents unavailable:

  • Polymyxin B or colistin-based combination therapy with two in vitro active agents 1, 3
  • Combination options include: polymyxin + carbapenem (if MIC ≤8 mg/L), polymyxin + fosfomycin, or polymyxin + aminoglycoside 3, 5
  • Case reports demonstrate success with colistin + fosfomycin + doxycycline for difficult-to-treat infections 6

Non-severe infections or lower-risk patients:

• Meropenem 1 g IV every 8 hours (if susceptible) 1
• Imipenem/cilastatin 1 g IV every 8 hours (if susceptible) 1
• Doripenem 500 mg IV every 8 hours (if susceptible) 1

For Extended-Spectrum Beta-Lactamase (ESBL) Klebsiella

Patients with healthcare-associated risk factors (recent antibiotics, nursing home residence, indwelling catheters):

• Carbapenem therapy: meropenem 1 g IV every 8 hours or imipenem/cilastatin 1 g IV every 8 hours 1
• Ampicillin 2 g IV every 6 hours should be added for enterococcal coverage in intra-abdominal infections 1

Carbapenem-sparing regimens for non-critically ill patients:

• Piperacillin-tazobactam 4.5 g IV every 6 hours + tigecycline 100 mg loading dose, then 50 mg IV every 12 hours 1
• Ceftolozane-tazobactam 1.5 g IV every 8 hours (if active in vitro) 1, 3

Critical Pitfalls and Caveats

Avoid tigecycline monotherapy for bacteremia or pneumonia due to inadequate serum concentrations and documented increased mortality risk 1, 3

Do not use polymyxin-rifampin combinations as strong evidence demonstrates lack of benefit and potential harm 1

For polymyxin therapy, nephrotoxicity monitoring is mandatory with polymyxin B preferred over colistin due to lower nephrotoxicity rates (adjusted HR 2.27 for colistin) 3

Combination therapy is superior to monotherapy for severe CRKP infections, with meta-analyses showing reduced 28-30 day mortality (35.7% vs 55.5%; OR 0.46,95% CI 0.30-0.69) 3

Dosing Specifications for Key Agents

Ceftazidime-avibactam: 2.5 g (ceftazidime 2 g + avibactam 0.5 g) IV every 8 hours, with dose adjustment for renal impairment 2

Polymyxin B: Loading dose 9 MIU (5 mg/kg), then maintenance 4.5 MIU twice daily for critically ill patients 3

Meropenem for high-dose extended-infusion: 1 g IV every 8 hours, consider 2 g every 8 hours as extended infusion for severe infections 1

Treatment Duration

Intra-abdominal infections: 5-14 days depending on source control and clinical response 2

Osteomyelitis: Minimum 3 months of combination therapy documented as effective 6

Bacteremia: Minimum 14 days, extended to 4-6 weeks for complicated bacteremia with metastatic foci 7

Adjunctive Measures

For respiratory tract infections with CRKP, consider adding aerosolized polymyxin to intravenous therapy, which may reduce mortality (RR 0.86) and clinical treatment failure (RR 0.82) 3

Source control is mandatory for intra-abdominal infections, with percutaneous drainage or surgical intervention as clinically indicated 1