What are the infections caused by the family Enterobacteriaceae (Enterobacteriaceae family)?

From the Guidelines

Infections caused by the family Enterobacteriaceae should be managed with empiric antibiotic therapy based on the clinical condition of the patient, individual risk for infection by resistant pathogens, and local resistance epidemiology, with a focus on preserving the activity of carbapenems and other broad-spectrum antibiotics. The management of infections caused by Enterobacteriaceae, such as Escherichia coli and Klebsiella pneumoniae, is a complex issue due to the increasing prevalence of antimicrobial resistance, including extended-spectrum beta-lactamases (ESBLs) and carbapenemases 1. Key considerations in the treatment of these infections include:

• The distinction between community-acquired and healthcare-associated infections, with the latter often requiring broader-spectrum antibiotic coverage due to the higher risk of resistant organisms 1.
• The use of antimicrobial agents with activity against ESBL-producing Enterobacteriaceae, such as carbapenems, in patients at risk for these infections 1.
• The importance of local epidemiology and resistance patterns in guiding empiric antibiotic selection, as highlighted in the 2017 WSES guidelines for the management of intra-abdominal infections 1. Some of the key antibiotics used in the treatment of Enterobacteriaceae infections include:
• Third-generation cephalosporins, such as ceftriaxone, which may be used in combination with metronidazole for the treatment of mild to moderate infections 1.
• Carbapenems, such as meropenem, which are often reserved for the treatment of complicated infections or those caused by ESBL-producing organisms 1.
• Newer antibiotics, such as ceftolozane/tazobactam and ceftazidime/avibactam, which have been approved for the treatment of complicated intra-abdominal infections, including those caused by ESBL-producing Enterobacteriaceae and Pseudomonas aeruginosa 1. The prevention of Enterobacteriaceae infections and the spread of antimicrobial resistance requires a multifaceted approach, including:
• Proper hand hygiene and infection control practices in healthcare settings 1.
• Appropriate use of antibiotics, including the selection of narrow-spectrum agents whenever possible and the avoidance of unnecessary antibiotic use 1.
• Implementation of antibiotic stewardship programs to promote the rational use of antibiotics and reduce the emergence of resistant strains 1.

From the FDA Drug Label

Ciprofloxacin Tablets USP, 250 mg, 500 mg and 750 mg is indicated for the treatment of infections caused by susceptible strains of the designated microorganisms in the conditions and patient populations listed below. Adult Patients: Urinary Tract Infections caused by Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Serratia marcescens, Proteus mirabilis, Providencia rettgeri, Morganella morganii, Citrobacter diversus, Citrobacter freundii, Lower Respiratory Tract Infections caused by Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Proteus mirabilis, Pseudomonas aeruginosa, Skin and Skin Structure Infections caused by Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Proteus mirabilis, Bone and Joint Infections caused by Enterobacter cloacae, Complicated Intra-Abdominal Infections (used in combination with metronidazole) caused by Escherichia coli, Pseudomonas aeruginosa, Proteus mirabilis, Klebsiella pneumoniae

Infections caused by family Enterobacteriaceae are treated with ciprofloxacin, including:

• Urinary Tract Infections caused by Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae
• Lower Respiratory Tract Infections caused by Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae
• Skin and Skin Structure Infections caused by Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae
• Bone and Joint Infections caused by Enterobacter cloacae
• Complicated Intra-Abdominal Infections caused by Escherichia coli, Klebsiella pneumoniae

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From the Research

Infections Caused by Family Enterobacteriaceae

Infections caused by the family Enterobacteriaceae are a significant concern due to the increasing resistance to antibiotics. The following points highlight the key aspects of these infections:

• The family Enterobacteriaceae has undergone significant changes in its taxonomy, with new species being described and some established species being observed in new infectious disease settings and syndromes 3.
• Extended-spectrum β-lactamases (ESBL) and AmpC β-lactamases are increasing causes of resistance in many Gram-negative pathogens of common infections, leading to a growing utilization of broad spectrum antibiotics, most predominately the carbapenem agents 4.
• The optimal treatment for ESBL-producing Enterobacteriaceae bloodstream infections has yet to be defined, with retrospective studies showing conflicting results, and most data suggesting the non-inferiority of beta-lactam-beta-lactamase inhibitor combinations compared with carbapenems 5.

Treatment Options

The treatment options for infections caused by Enterobacteriaceae that express extended-spectrum β-lactamase and AmpC enzymes are limited. The following points highlight the key treatment options:

• Carbapenems are often used to treat ESBL-producing Enterobacteriaceae infections, but their overuse has led to the increasing carbapenem-resistant Enterobacteriaceae 6.
• Beta-lactam-beta-lactamase inhibitor combinations, such as piperacillin-tazobactam, may be effective alternatives to carbapenems for the treatment of ESBL-producing Enterobacteriaceae infections 4, 5.
• Cefepime (FEP) has been shown to be a clinically useful carbapenem-sparing alternative for the treatment of infections caused by AmpC-producing Enterobacteriaceae 4.

Challenges and Future Directions

The management of infections caused by Enterobacteriaceae that express extended-spectrum β-lactamase and AmpC enzymes presents several challenges. The following points highlight the key challenges and future directions:

• The production of β-lactamase is the principal mechanism by which gram-negative bacteria resist the action of β-lactam antibiotics, and the diversity, global dissemination, host range, and spectrum of activity of β-lactamases are increasing 7.
• The selection of appropriate antimicrobial therapy is challenging due to the limited treatment options and the need for susceptibility testing 7.
• Further research is needed to develop new and effective treatment options for infections caused by Enterobacteriaceae that express extended-spectrum β-lactamase and AmpC enzymes 6, 5.