Resistant Bacterial Infections: Guidelines From the Infectious Diseases Society of America

Antimicrobial resistance is a global crisis, and resistant pathogens cause more than 2.8 million infections and 35,000 deaths annually. Even when bacterial cultures indicate resistance, choosing the most effective antibiotic can be challenging. The Infectious Diseases Society of America published guidelines for treating infections with the most common resistant gram-negative organisms. These guidelines do not apply to empiric treatment.

For this guideline, complicated urinary tract infections (UTIs) are defined as occurring in males or females with a genitourinary tract abnormality. After removal of hardware or treatment of urinary stasis, complicated UTI can be treated as uncomplicated.

Enterobacterales are gram-negative rods that are common in the gastrointestinal tract and have several common resistance patterns. Common pathogens include Escherichia coli, Proteus, Klebsiella, Salmonella, and Shigella.

ESBL-Producing Enterobacterales

Extended-spectrum beta-lactamase (ESBL)–producing Enterobacterales have enzymes that act against most penicillins, cephalosporins, and aztreonam but are generally susceptible to carbapenems. Non–beta-lactam agents (such as fluoroquinolones and trimethoprim/sulfamethoxazole [TMP/SMX]) are not inactivated unless organisms carry additional mutations. Enterobacterales that are most likely to produce this enzyme include E. coli, Klebsiella pneumoniae, Klebsiella oxytoca, and Proteus mirabilis. Ceftriaxone susceptibility is usually used as a proxy to identify ESBL-producing Enterobacterales.

Carbapenem-Resistant Enterobacterales

Carbapenem-resistant Enterobacterales (CREs) demonstrate resistance to meropenem or imipenem or isolate-producing carbapenemase enzymes. When susceptibility testing shows resistance to ertapenem, but not meropenem and imipenem, meropenem is recommended for mild infections.

AmpC Beta-Lactamase–Producing Enterobacterales

Enterobacter cloacae complex, Klebsiella aerogenes, and Citrobacter freundii are the most common Enterobacterales to have induced resistance through increased AmpC.

For infections caused by organisms at high likelihood of induced AmpC resistance, guidelines suggest treatment with cefepime. If cefepime resistance is documented, a carbapenem should be used. Ceftriaxone should not be used when these organisms are present because of high induction of AmpC. Medication combining beta-lactams and beta-lactamase inhibitors can be used in cases of carbapenem resistance, although combinations that include tazobactam should be avoided. Non–beta-lactam medications can be used for these infections.

Treating Infections Caused by Resistant Enterobacterales

Uncomplicated UTI. Nitrofurantoin and TMP/SMX are safe, effective, and preferred in uncomplicated cystitis. A single intravenous dose of an aminoglycoside is an alternative that appears to be effective with minimal toxicity. To prevent development of resistance, carbapenems, ciprofloxacin, and levofloxacin should be avoided in uncomplicated cystitis. Amoxicillin/clavulanate and doxycycline are not recommended because of a lack of clinical research on effectiveness. Colistin is an alternative treatment for CRE, although there is a risk of nephrotoxicity.