What are the implications of increased use of Carbapenem (carbapenem) and Colistin (colistin)?

From the Guidelines

The use of carbapenems and colistin should be reserved for severe infections caused by multidrug-resistant organisms, and their use should be guided by antimicrobial stewardship programs to minimize the risk of resistance development and optimize patient outcomes. The increasing use of carbapenems and colistin is a concern due to the rise of multidrug-resistant organisms, including extended-spectrum beta-lactamase (ESBL) producing organisms and carbapenem-resistant Enterobacteriaceae (CRE) 1.

Key Considerations

• Carbapenems are broad-spectrum beta-lactam antibiotics that work by inhibiting cell wall synthesis in bacteria, while colistin is a polymyxin antibiotic that disrupts bacterial cell membranes.
• The main driver behind their increased use is the global spread of ESBL producing organisms and CRE.
• Healthcare providers should use these medications judiciously, implementing antimicrobial stewardship programs that include appropriate culture collection before starting therapy, de-escalation when possible, and limiting treatment duration to the minimum necessary period 1.
• The overuse of these critical antibiotics accelerates resistance development, creating a dangerous cycle where increasingly powerful antibiotics become ineffective, leaving few treatment options for severe infections and potentially returning us to a pre-antibiotic era for some pathogens.

Treatment Options

• For patients with infections caused by KPC-producing carbapenem-resistant Enterobacterales (CRE), novel β-lactam agents such as ceftazidime/avibactam and meropenem/vaborbactam should be the first-line treatment options 1.
• Imipenem/relebactam and cefiderocol may also be considered as potential alternatives for the treatment of infections involving KPC-producing CRE.
• Colistin-based combination therapy, such as colistin-meropenem, may be considered for the treatment of infections due to carbapenem-resistant Acinetobacter baumannii 1.

Duration of Treatment

• The duration of treatment should be individualized based on the patient's clinical response and the severity of the infection.
• For pneumonia, treatment should be continued for at least 7 days, while for bloodstream infections, treatment should be continued for 10-14 days 1.

Antimicrobial Stewardship

• Antimicrobial stewardship programs should be implemented to minimize the risk of resistance development and optimize patient outcomes.
• These programs should include appropriate culture collection before starting therapy, de-escalation when possible, and limiting treatment duration to the minimum necessary period 1.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Increased Use of Carbapenem and Colistin

• The use of carbapenem and colistin has increased due to the rising resistance to carbapenems, which is a major concern in public health 2.
• Carbapenem-resistant gram-negative bacteria, such as Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter baumannii, are a significant threat, and colistin is often used as a first-line agent for treatment 2.
• However, the efficacy of colistin, even when used in combination with other agents, is uncertain, and new agents with activity against carbapenem-resistant pathogens have been approved for clinical use 2.

Clinical Efficacy of Colistin and Carbapenem Combinations

• Studies have shown that combination therapy with colistin and meropenem is not superior to colistin monotherapy for the treatment of severe infections caused by carbapenem-resistant Gram-negative bacteria 3, 4.
• The OVERCOME trial found no difference in 28-day mortality, clinical failure, and microbiologic cure between patients receiving colistin monotherapy and combination therapy with meropenem 4.
• Another study found that combination therapy increased the incidence of diarrhea and decreased the incidence of mild renal failure, but did not improve clinical outcomes 3.

Alternatives to Colistin and Carbapenem

• New agents, such as ceftazidime-avibactam and meropenem-vaborbactam, have been approved for the treatment of carbapenem-resistant Enterobacteriaceae (CRE) infections, and have shown higher rates of clinical cure and decreased mortality compared to colistin-based regimens 5.
• These agents have different in vitro activity and mechanisms of resistance, and clinicians need to be aware of their differences when selecting treatment options 5.

Considerations for Antibiotic Stewardship

• The increased use of carbapenem and colistin highlights the need for antibiotic stewardship programs to ensure appropriate and rational use of these agents 2.
• Hospital formularies and antibiotic stewardship programs should consider the differences between ceftazidime-avibactam and meropenem-vaborbactam, as well as the potential for selection of resistance, when positioning these agents for use 5.