Inpatient antibiotic resistance: Everyone’s problem

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Inpatient antibiotic resistance: Everyone’s problem

J Fam Pract. 2018 February;67(2):E1-E11

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From The Journal of Family Practice | 2018;67(2):E1-E11.

References

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Multi-drug resistant Pseudomonas aeruginosa

Pseudomonas aeruginosa is a gram-negative rod that can be isolated from nosocomial infections such as UTIs, bacteremias, pneumonias, skin and skin structure infections, and burn infections.²⁰ Pseudomonal infections are associated with high morbidity and mortality and can cause recurrent infections in patients with cystic fibrosis.²⁰ Multidrug-resistant P. aeruginosa (MDR-P) infections account for approximately 13% of all health care-associated pseudomonal infections nationally.¹ Both fluoroquinolone and aminoglycoside resistance has emerged, and multiple types of beta-lactamases (ESBL, AmpC, carbapenemases) have resulted in organisms that are resistant to nearly all anti-pseudomonal beta-lactams.²⁰

Treatment. For patients at risk for MDR-P, some clinical practice guidelines have recommended using an empiric therapy regimen that contains antimicrobial agents from 2 different classes with activity against P. aeruginosa to increase the likelihood of susceptibility to at least one agent.⁶ De-escalation can occur once culture and susceptibility results are available.⁶ Dose optimization based on pharmacodynamic principles is critical for ensuring clinical efficacy and minimizing resistance.³⁶ The use of high-dose, prolonged-infusion beta-lactams (piperacillin/tazobactam, cefepime, ceftazidime, and carbapenems) is becoming common practice at institutions with higher rates of resistance.^36-38

A resurgence of polymyxin (colistin) use for MDR-P isolates has occurred, and may be warranted empirically in select patients, based on local resistance patterns and patient history. Newer pharmacokinetic data are available, resulting in improved dosing strategies that may enhance efficacy while alleviating some of the nephrotoxicity concerns associated with colistin therapy.³⁹

Ceftolozane/tazobactam (Zerbaxa) and ceftazidime/avibactam (Avycaz) are options for complicated urinary tract and intra-abdominal infections caused by susceptible P. aeruginosa isolates. Given the lack of comparative efficacy data available for the management of MDR-P infections, agent selection should be based on site of infection, susceptibility data, and patient-specific factors.

Multi-drug resistant Acinetobacter baumannii

A. baumannii is a lactose-fermenting, gram-negative rod sometimes implicated in nosocomial pneumonias, line-related bloodstream infections, UTIs, and surgical site infections.²⁰ Resistance has been documented for nearly all classes of antibiotics, including carbapenems.^1,20 Over half of all health care-associated A. baumannii isolates in the United States are multidrug resistant.¹

Treatment. Therapy options for A. baumannii infections are often limited to polymyxins, tigecycline, carbapenems (except ertapenem), aminoglycosides, and high-dose ampicillin/sulbactam, depending on in vitro susceptibilities.^40,41When using ampicillin/sulbactam for A. baumannii infections, sulbactam is the active ingredient. Doses of 2 to 4 g/d of sulbactam have demonstrated efficacy in non-critically ill patients, while critically ill patients may require higher doses (up to 12 g/d).⁴⁰ Colistin is considered the mainstay of therapy for carbapenem-resistant A. baumannii. It should be used in combination with either a carbapenem, rifampin, an aminoglycoside, or tigecycline.⁴²

Drug therapies for nosocomial-resistant gram-negative infections, along with clinical pearls for use, are summarized in TABLE 3.^{20,22,23,25,27-42} Because efficacy data are limited for treating infections caused by these pathogens, appropriate antimicrobial selection is frequently guided by location of infection, susceptibility patterns, and patient-specific factors such as allergies and the risk for adverse effects.

Antimicrobial stewardship

Antibiotic misuse has been a significant driver of antibiotic resistance.⁴⁶ Efforts to improve and measure the appropriate use of antibiotics have historically focused on acute care settings. Broad interventions to reduce antibiotic use include prospective audit with intervention and feedback, formulary restriction and preauthorization, and antibiotic time-outs.^47,48

Multidrug-resistant Pseudomonas aeruginosa infections account for approximately 13% of all health care-associated pseudomonal infections nationally.

Pharmacy-driven interventions include intravenous-to-oral conversions, dose adjustments for organ dysfunction, pharmacokinetic or pharmacodynamic interventions to optimize treatment for organisms with reduced susceptibility, therapeutic duplication alerts, and automatic-stop orders.^47,48

Diagnosis-specific interventions include order sets for common infections and the use of rapid diagnostic assays (TABLE 4^49,50). Rapid diagnostic testing is increasingly being considered an essential component of stewardship programs because it permits significantly shortened time to organism identification and susceptibility testing and allows for improved antibiotic utilization and patient outcomes when coupled with other effective stewardship strategies.⁴⁹