What is the relationship between Extended-Spectrum Beta-Lactamases (ESBL) and Ampicillin (AMP) resistance in bacteria?

From the Guidelines

For infections caused by ESBL-producing organisms, carbapenems (ertapenem 1g IV daily, meropenem 1g IV q8h, or imipenem 500mg IV q6h) are the treatment of choice, as recommended by the most recent guidelines 1.

Key Considerations

• ESBLs are primarily found in Enterobacteriaceae like E. coli and Klebsiella, while AmpC enzymes occur naturally in organisms like Enterobacter and Citrobacter but can also be acquired by other bacteria.
• For less severe infections, alternatives include piperacillin-tazobactam (4.5g IV q6h) or ceftazidime-avibactam (2.5g IV q8h) 1.
• AmpC-producing organisms are typically resistant to cephalosporins and penicillins but remain susceptible to carbapenems, which are the preferred treatment.
• Fluoroquinolones (ciprofloxacin 400mg IV q12h) or aminoglycosides may be effective if susceptibility is confirmed.
• Treatment duration typically ranges from 7-14 days depending on infection site and severity.

Infection Control Measures

• Infection control measures including contact precautions, hand hygiene, and antimicrobial stewardship are essential to prevent the spread of these resistant organisms in healthcare settings 1.
• The use of carbapenems should be limited to preserve their activity, and carbapenem-sparing regimens should be considered when possible 1.

New Treatment Options

• New antibiotics like ceftolozane/tazobactam and ceftazidime/avibactam have been approved for the treatment of IAIs, including infections caused by ESBL-producing Enterobacteriaceae and P. aeruginosa 1.
• These new agents should be combined with metronidazole for complicated IAIs due to limited activity against some Bacteroides spp.

From the FDA Drug Label

AVYCAZ demonstrated in vitro activity against Enterobacteriaceae in the presence of some beta-lactamases and extended-spectrum beta-lactamases (ESBLs) of the following groups: TEM, SHV, CTX-M, Klebsiella pneumoniae carbapenemase (KPCs), AmpC, and certain oxacillinases (OXA). ZERBAXA demonstrated in vitro activity against Enterobacteriaceae in the presence of some extended-spectrum beta-lactamases (ESBLs) and other beta-lactamases of the following groups: TEM, SHV, CTX-M, and OXA. ZERBAXA demonstrated in vitro activity against P. aeruginosa isolates tested that had chromosomal AmpC, loss of outer membrane porin (OprD), or up regulation of efflux pumps (MexXY, MexAB)

ESBL and AmpC activity is demonstrated by both AVYCAZ and ZERBAXA in vitro.

• AVYCAZ is active against ESBLs of the groups: TEM, SHV, CTX-M, KPCs, AmpC, and certain oxacillinases (OXA) 2.
• ZERBAXA is active against ESBLs of the groups: TEM, SHV, CTX-M, and OXA, and also against P. aeruginosa with chromosomal AmpC 3. Key points:
• Both drugs have in vitro activity against ESBL-producing bacteria.
• Both drugs have in vitro activity against AmpC-producing bacteria.
• The clinical significance of this activity is not fully established, but it suggests that these drugs may be effective against certain bacteria that are resistant to other antibiotics.

From the Research

ESBL and AMP C Infections

• ESBL-producing Enterobacteriales are a major threat to public health worldwide, with carbapenems currently considered the first-line choice for serious ESBL infections 4.
• However, the overuse of carbapenems has led to the selection and spread of carbapenemases, making it essential to implement strategies to limit their use 4.
• Alternative treatments, such as piperacillin-tazobactam, ceftazidime-avibactam, and ceftolozane-tazobactam, may be effective for certain types of ESBL infections, but further clinical data are needed to establish their efficacy relative to carbapenems 4, 5.

Treatment Options

• Ceftazidime-avibactam and ceftolozane-tazobactam appear to be the best-available carbapenem-sparing therapies for ESBL infections 5.
• Cefepime (FEP) has been shown to be a clinically useful carbapenem-sparing alternative for the treatment of infections caused by AmpC-producing Enterobacteriaceae 6.
• Patient and infection-specific characteristics should be used to employ FEP optimally 6.

Characteristics and Epidemiology

• ESBL-producing Gram-negative pathogens are a major cause of resistance to expanded-spectrum β-lactam antibiotics, with CTX-M-type enzymes being the most commonly found ESBL type 7.
• The genes encoding ESBLs are often found on plasmids and harboured within transposons or insertion sequences, enabling their spread 7.
• The population of ESBL-producing Escherichia coli is dominated globally by a highly virulent and successful clone belonging to ST131 7.

Detection and Diagnosis

• Several diagnostic tools are available to detect β-lactamases, including both phenotypic and genotypic tests 7.
• Timely identification of ESBLs is essential to ensure appropriate antimicrobial therapy and prevent poor clinical outcomes 7.
• Surveillance studies are necessary to monitor the spread of ESBL-producing Gram-negative pathogens and inform treatment strategies 7, 8.