How to diagnose and treat ESBL vs MDRO infections?

From the Guidelines

Diagnosing and treating ESBL and MDRO infections requires a comprehensive approach that includes laboratory confirmation, appropriate antimicrobial therapy, and infection control measures to prevent spread and reduce resistance development. For diagnosis, collecting appropriate clinical samples (blood, urine, wound, etc.) and requesting specific susceptibility testing to identify these resistant organisms is crucial 1. Standard cultures may detect the presence of bacteria, but specialized tests like chromogenic media, molecular methods (PCR), or MALDI-TOF are needed to confirm ESBL production or multi-drug resistance patterns.

Key Considerations for Diagnosis and Treatment

• Laboratory confirmation is essential for guiding treatment decisions
• Susceptibility testing should be performed to identify the most effective antimicrobial agents
• Infection control measures, including contact precautions, hand hygiene, and patient isolation, are critical to prevent spread
• Antimicrobial stewardship is necessary to reduce selection pressure that promotes resistance development

Treatment Options for ESBL and MDRO Infections

• For ESBL infections, carbapenems are the treatment of choice, with meropenem (1g IV every 8 hours), imipenem (500mg IV every 6 hours), or ertapenem (1g IV daily) being most effective 1
• Alternative options include piperacillin-tazobactam (4.5g IV every 6 hours) for less severe infections or ceftazidime-avibactam (2.5g IV every 8 hours) for certain strains
• For MDROs, treatment must be guided by susceptibility testing, often requiring combinations like polymyxins (colistin 9 million units loading dose followed by 4.5 million units every 12 hours), tigecycline (100mg IV loading dose followed by 50mg every 12 hours), or newer agents like ceftolozane-tazobactam (1.5g IV every 8 hours) 1
• Treatment duration typically ranges from 7-14 days depending on infection site and severity

Recent Developments and Recommendations

• The use of carbapenems should be limited to preserve activity of this class of antibiotics due to the concern of emerging carbapenem-resistance 1
• Newer agents like ceftolozane-tazobactam and ceftazidime-avibactam have been approved for treatment of cIAIs (in combination with metronidazole) including infection by ESBLs producing Enterobacteriaceae and P. aeruginosa 1
• The recent challenges of treating multidrug-resistant gram-negative infections, especially in critically ill patients, have renewed interest in the use of “old” antibiotics such as polymyxins and fosfomycin 1

From the FDA Drug Label

Among Gram-negative uropathogens from both arms of Trial 2, genotypic testing identified certain ESBL groups (e.g., TEM-1, SHV-12, CTX-M-15, CTX-M-27, KPC-2, KPC-3, OXA-48) and AmpC beta-lactamases expected to be inhibited by avibactam in isolates from 273/281 (97. 2%) patients in the mMITT population. In a subset of Enterobacteriaceae isolates from both arms of the trial that met pre-specified criteria for beta-lactam susceptibility, genotypic testing identified certain ESBL groups (e.g., TEM, SHV, CTX-M, OXA) in 101/425 (23.8%).

Distinguishing between ESBL and MDRO infections requires genotypic testing to identify specific beta-lactamase groups.

• ESBL infections can be identified by the presence of certain ESBL groups, such as TEM, SHV, CTX-M, and OXA.
• MDRO infections are not directly addressed in the provided drug labels, but it can be inferred that MDRO infections may involve multiple drug resistance mechanisms, including beta-lactam resistance. The provided drug labels do not provide a clear distinction between ESBL and MDRO infections, but they do suggest that genotypic testing can help identify specific resistance mechanisms. 2 3

From the Research

Distinguishing between ESBL and MDRO Infections

To diagnose and treat ESBL (Extended-Spectrum Beta-Lactamase) vs MDRO (Multidrug-Resistant Organism) infections, it is essential to understand the characteristics of each.

• ESBL-producing organisms are resistant to most beta-lactam antibiotics, including penicillins, cephalosporins, and aztreonam 4.
• MDROs, on the other hand, are resistant to multiple classes of antibiotics, making treatment more challenging 5.

Diagnosis of ESBL and MDRO Infections

Diagnosis of ESBL and MDRO infections involves:

• Phenotypic testing, such as the Carba NP test, to detect carbapenemase production 6.
• Genotypic tests, such as PCR, to detect the presence of ESBL or carbapenemase genes 7.
• Minimum inhibitory concentration (MIC) testing to determine the susceptibility of the organism to various antibiotics 8.

Treatment of ESBL and MDRO Infections

Treatment options for ESBL and MDRO infections include:

• Carbapenems, such as meropenem or imipenem, which are often considered the drugs of choice for severe ESBL infections 4, 8.
• Beta-lactam/beta-lactamase inhibitor combinations, such as piperacillin/tazobactam or ceftazidime/avibactam, which may be effective against some ESBL-producing organisms 8, 7.
• Newer agents, such as ceftolozane/tazobactam or cefiderocol, which have shown efficacy against MDROs, including carbapenem-resistant Enterobacteriaceae (CRE) 6.
• Combination therapy, which may be necessary for the treatment of complex MDRO infections 5, 6.

Key Considerations

• Accurate and rapid diagnosis of ESBL and MDRO infections is crucial for effective treatment 6, 7.
• Antimicrobial stewardship is essential to prevent the overuse and misuse of antibiotics, which can contribute to the development of resistance 5, 8.
• Continuous surveillance and monitoring of ESBL and MDRO infections are necessary to track the spread of resistance and inform treatment guidelines 7.