What is the recommended antimicrobial management for a 74‑year‑old woman on thrice‑weekly hemodialysis with a carbapenem‑resistant Klebsiella pneumoniae (KPC) isolate of 100,000 CFU?

Management of Carbapenem-Resistant Klebsiella pneumoniae (KPC) in a Hemodialysis Patient

Initiate ceftazidime-avibactam 2.5 g IV every 48 hours (adjusted for hemodialysis) as first-line therapy for this KPC-producing K. pneumoniae isolate, with supplemental dosing after each dialysis session. 1, 2

First-Line Treatment Selection

• Ceftazidime-avibactam is the preferred agent for KPC-producing K. pneumoniae, demonstrating 28-day mortality of 18.3% versus 40.8% with alternative agents (p=0.005). 1, 2

• Meropenem-vaborbactam 4 g IV every 48 hours (hemodialysis-adjusted) represents an equally effective alternative, particularly if the infection involves the respiratory tract where epithelial lining fluid penetration is superior. 1, 2

• Both agents show significantly lower nephrotoxicity compared to colistin-based regimens, a critical consideration in this dialysis-dependent patient. 1, 2

Hemodialysis-Specific Dosing Considerations

• Administer supplemental doses of ceftazidime-avibactam (1.25 g) immediately after each hemodialysis session, as both ceftazidime and avibactam are removed by dialysis. 2

• For meropenem-vaborbactam, give 2 g after each dialysis session if this agent is selected. 2

• Avoid aminoglycosides as monotherapy despite urinary concentrations 25-100× plasma levels, because this patient's twice-weekly dialysis schedule increases nephrotoxicity risk and complicates therapeutic drug monitoring. 2, 3

Determining Infection Site and Severity

• Obtain rapid molecular testing immediately to confirm KPC production versus other carbapenemase types (OXA-48, MBL), as each requires distinct therapy. 1, 2

• If this represents asymptomatic bacteriuria (100,000 CFU without symptoms), treatment may not be indicated; however, if symptomatic UTI, pyelonephritis, or bacteremia is present, proceed with antimicrobial therapy. 2

• For uncomplicated cystitis: treat 5-7 days; complicated UTI: 5-7 days; pyelonephritis: 7-14 days; bacteremia: minimum 7-14 days. 1, 2

Combination Therapy Decision Algorithm

• Reserve combination therapy (ceftazidime-avibactam PLUS a second active agent) for severe presentations: septic shock, ICU admission, or high mortality risk, where dual therapy reduces 30-day mortality (adjusted HR 0.56,95% CI 0.34-0.91). 1, 2

• For non-severe infections, monotherapy with ceftazidime-avibactam or meropenem-vaborbactam is sufficient. 1, 2

• If combination therapy is required, add a carbapenem (high-dose extended-infusion meropenem 2 g over 3 hours every 48 hours post-dialysis) or consider double-carbapenem regimens when options are limited. 1, 2

Alternative Agents When First-Line Unavailable

• Imipenem-cilastatin-relebactam 1.25 g IV adjusted for hemodialysis represents the next alternative for KPC-producing isolates. 1, 2

• Cefiderocol may be employed as salvage therapy, with 96% susceptibility against carbapenem-resistant K. pneumoniae in recent surveillance. 1

• Avoid colistin monotherapy: mortality approaches 33% and clinical/microbiological response <70%, with significant nephrotoxicity risk in this dialysis patient. 2, 4

Critical Resistance Monitoring

• Ceftazidime-avibactam resistance emerges in 0-12.8% of KPC-producing isolates during treatment, particularly with KPC D179Y mutations; if resistance develops, switch immediately to meropenem-vaborbactam. 1, 2, 5

• *Repeat susceptibility testing if clinical failure occurs within 72 hours, as KPC variants can confer resistance through deletions in the blaKPC gene.* 1, 5

Special Considerations for Metallo-β-Lactamase Producers

• If rapid molecular testing identifies MBL production (not KPC), switch to ceftazidime-avibactam 2.5 g PLUS aztreonam 2 g, both adjusted for hemodialysis, as this combination achieves 70-90% efficacy against MBL producers. 1, 2, 6

• MBL-producing strains render ceftazidime-avibactam and meropenem-vaborbactam ineffective as monotherapy. 1, 2

Infectious Diseases Consultation

• Obtain infectious diseases consultation for all carbapenem-resistant K. pneumoniae infections to optimize antimicrobial selection, dosing in hemodialysis, and source control assessment. 2

Common Pitfalls to Avoid

• Do not use piperacillin-tazobactam for carbapenem-resistant K. pneumoniae, even if in vitro susceptibility is reported; clinical failures are well-documented. 2, 4

• Do not rely on standard carbapenem dosing; high-dose extended-infusion regimens (3-hour infusions) are mandatory for isolates with elevated MICs to maximize time above MIC. 1, 2

• Do not use tigecycline for bacteremia or pneumonia; it performs poorly in bloodstream infections despite in vitro susceptibility. 2, 4

• Do not assume carbapenem susceptibility based on routine testing; KPC-producing strains may show MICs in the susceptible range yet cause clinical failures. 4, 7