Why is Augmentin (amoxicillin-clavulanate) prescribed in combination with Ciprofloxacin for a wound culture positive for Enterobacter cloacae that is sensitive to these antibiotics?

From the Guidelines

For Enterobacter cloacae wound infection, I recommend using ciprofloxacin alone rather than combining it with augmentin (amoxicillin-clavulanate). Ciprofloxacin at 500-750 mg orally twice daily for 7-14 days (depending on infection severity) would be appropriate if the organism is sensitive 1. Adding augmentin is generally not recommended because Enterobacter species typically have chromosomal AmpC beta-lactamases that can be induced during treatment with beta-lactam/beta-lactamase inhibitor combinations like augmentin, potentially leading to treatment failure even if initially reported as sensitive. This phenomenon, called inducible resistance, is why many infectious disease specialists avoid beta-lactams for definitive Enterobacter therapy.

Some key points to consider in the management of intra-abdominal infections and wound infections include:

• The choice of empiric antibiotic regimens should be based on the clinical condition of the patients, the individual risk for infection by resistant pathogens, and the local resistance epidemiology 1.
• In patients with uncomplicated infections, single doses or short courses of antibiotic therapy may be sufficient, but in critically ill patients, an individualized approach should be taken, considering the pathophysiological status of the patient and the pharmacokinetic properties of the employed antibiotics 1.
• The use of carbapenems should be limited to preserve the activity of this class of antibiotics due to the concern of emerging carbapenem-resistance 1.
• New antibiotics such as ceftolozone/tazobactam and ceftazidime/avibactam have been approved for the treatment of complicated intra-abdominal infections, including infections by ESBL-producing Enterobacteriaceae and P. aeruginosa 1.

If combination therapy is truly desired, ciprofloxacin plus trimethoprim-sulfamethoxazole would be a more appropriate choice if the organism is sensitive to both. Ensure adequate wound care continues during antibiotic therapy, and follow-up cultures may be warranted if the infection doesn't improve appropriately. The most recent and highest quality study 1 supports the use of ciprofloxacin alone for the treatment of Enterobacter cloacae wound infections, and this approach should be prioritized to minimize the risk of inducible resistance and treatment failure.

From the FDA Drug Label

Amoxicillin/clavulanic acid has been shown to be active against most isolates of the following bacteria, both in vitro and in clinical infections... Gram-negative bacteria... Enterobacter species The formulation of amoxicillin and clavulanate potassium tablets protects amoxicillin from degradation by some beta-lactamase enzymes and extends the antibiotic spectrum of amoxicillin to include many bacteria normally resistant to amoxicillin 1.5 Urinary Tract Infections – caused by beta-lactamase–producing isolates of E. coli, Klebsiella species, and Enterobacter species.

Augmentin (amoxicillin-clavulanate) is used to treat infections caused by beta-lactamase-producing bacteria, including Enterobacter species. The addition of clavulanic acid to amoxicillin protects amoxicillin from degradation by beta-lactamase enzymes, extending its spectrum of activity to include bacteria that would otherwise be resistant.

• The dose of Augmentin is not specified in the provided text, but it is typically administered as 500 mg/125 mg or 875 mg/125 mg tablets, every 12 hours or every 8 hours.
• The choice of Augmentin in combination with ciprofloxacin may be due to the fact that Enterobacter cloacae can produce beta-lactamases, making amoxicillin alone ineffective. The use of clavulanic acid helps to overcome this resistance. 2 2

From the Research

Rationale for Augmentin Use

• The use of Augmentin (amoxicillin-clavulanate) in treating Enterobacter cloacae infections is based on its broad antibacterial activity against gram-positive, gram-negative, and anaerobic bacteria 3.
• Although Enterobacter cloacae has shown resistance to ampicillin and amoxicillin-clavulanate in some studies, the combination of amoxicillin-clavulanate with ciprofloxacin may still be effective in treating infections caused by this bacterium 4, 5.

Dosing of Augmentin

• The dosing of Augmentin associated with its use has been revised by the Clinical and Laboratory Standards Institute (CLSI) Subcommittee on Antimicrobial Susceptibility Testing 3.
• However, the exact dosing of Augmentin for Enterobacter cloacae infections is not specified in the provided studies.

Antibiotic Resistance

• Enterobacter cloacae has been shown to exhibit resistance to various antibiotics, including ampicillin, amoxicillin-clavulanate, cephalothin, cefuroxime, and cefoxitin 4.
• The use of carbapenems, such as meropenem, imipenem, and ertapenem, may be effective in treating Enterobacter cloacae infections, but potential future resistance against these antibiotics should be considered 4, 6.

Treatment Outcomes

• The combination of ciprofloxacin with other antibiotics, such as carbapenems or cefepime, has been shown to be effective in treating Enterobacter cloacae infections 5, 6.
• The success rate of treatment for Enterobacter cloacae infections may be increased when ciprofloxacin is used in combination with other antibiotics 5.