What is the treatment for a blood infection with New Delhi metallo-beta-lactamase (NDM)-producing bacteria detected?

Treatment of Blood Infections with NDM-Producing Bacteria

For blood infections caused by NDM-producing bacteria, ceftazidime-avibactam combined with aztreonam is the preferred first-line treatment due to significantly lower mortality rates compared to other antimicrobial therapies. 1, 2

First-Line Treatment Options

• Ceftazidime-avibactam plus aztreonam is the recommended first-line therapy for NDM-producing bacterial infections, with studies showing 30-day mortality rates of 19.2% versus 44% with other antimicrobial therapies 1, 2
• This combination works synergistically because aztreonam is not hydrolyzed by metallo-β-lactamases, while avibactam inhibits other β-lactamases that might otherwise inactivate aztreonam 3
• Treatment should be initiated promptly after appropriate cultures are obtained, as delays in effective therapy are associated with increased mortality 1

Alternative Treatment Options

• Cefiderocol may be considered as an alternative option for NDM-producing infections, though with lower certainty of evidence 1, 2
• Fosfomycin shows promising in vitro activity against NDM-producing E. coli (98% susceptibility) and could be considered as part of combination therapy, particularly for urinary source infections 4
• Tigecycline (86.5% susceptible), eravacycline (66.2% susceptible), and omadacycline (59.6% susceptible) may be options in selected cases based on susceptibility testing 5
• Polymyxins (colistin and polymyxin B) may be added to combination regimens for synergistic effects, particularly in severe infections 6

Diagnostic Considerations

• Accurate microbiological diagnosis is essential before initiating therapy 3
• Susceptibility testing should be performed for all isolates, with particular attention to aztreonam, ceftazidime-avibactam, polymyxins, tigecycline, and fosfomycin 3, 5
• For metallo-β-lactamase detection, molecular methods are preferred over phenotypic tests due to higher accuracy 7
• Blood cultures should be repeated to document clearance of bacteremia 1

Treatment Duration and Monitoring

• Treatment duration typically ranges from 7-14 days depending on source control and clinical response 1
• Monitor renal function closely, particularly when using nephrotoxic agents like polymyxins 1
• Regular clinical assessment for treatment response is essential, with consideration for source control procedures if improvement is not observed 1
• Follow-up cultures may be helpful to document microbiological clearance 1

Source Control Considerations

• Aggressive source control is critical for successful treatment of NDM-producing bacterial infections 1
• Removal of infected devices (central lines, urinary catheters) is strongly recommended 1
• Surgical drainage of abscesses or other collections should be performed when present 1

Infection Control Measures

• Implement strict contact precautions for all patients with NDM-producing organisms 1
• Dedicate medical equipment to affected patients 1
• Enhanced environmental cleaning is essential to prevent transmission 1
• Active surveillance may be warranted for high-risk units during outbreaks 1
• Antimicrobial stewardship to limit unnecessary antibiotic exposure is crucial 1

Special Considerations

• Triple combination therapy with polymyxin B added to aztreonam plus ceftazidime-avibactam may provide enhanced bacterial killing and reduced inflammation in severe infections 6
• Novel de-escalation approaches to polymyxin B dosing (50% maintenance dose after standard loading) may reduce toxicity while maintaining efficacy 6
• All NDM-producing isolates should be considered multidrug-resistant, with 42.2% being extensively drug-resistant 5

Pitfalls and Caveats

• Avoid monotherapy for NDM-producing infections as it is associated with treatment failure and resistance development 6
• Do not rely solely on phenotypic tests for NDM detection as they have limited positive predictive value 7
• Be aware that NDM-producing bacteria with additional resistance mechanisms (e.g., PBP3 insertions) may have reduced susceptibility to aztreonam/avibactam combinations 4
• Recognize that treatment options are severely limited, emphasizing the importance of prevention and early aggressive therapy 5