Improving Antimicrobial Stewardship in the Management of Respiratory Infections

Antimicrobial resistance is a growing threat to public health. According to the US Centers for Disease Control and Prevention, at least 2 million Americans contract an antibiotic-resistant bacterial infection each year, and about 23,000 of these patients die.¹

The antibiotic resistance crisis has arisen because of anti­biotic overuse and misuse,² and antimicrobial stewardship represents a vital initiative to help combat it. Antimicrobial stewardship is composed of coordinated strategies designed to improve the appropriateness of antimicrobial use, aiming not only to reduce resistance to antimicrobial agents but also to enhance patient care.²

Interventions are especially needed to improve antibiotic use for common indications such as lower respiratory tract infections. These infections are a major public health problem in many countries, causing significant morbidity and mortality.³ And, according to Mary A. Musgrove, PharmD, of Henry Ford Hospital, Detroit, Michigan, and colleagues, about one-third of antibiotics administered in US hospitals are used to treat lower respiratory tract infections.⁴

In an interview with Contagion®, Susan L. Davis, PharmD, also of Henry Ford Hospital, said that antimicrobial therapy in pneumonia is largely empiric. “Decisions about de-escalation can be difficult when the pathogen isn’t clear,” she said, “which creates some challenges for antimicrobial stewardship programs.”

TREATMENT DECISIONS SHOULD BE DATA DRIVEN

Antibiotic prophylaxis is an important component of antibiotic use in lower respiratory tract infections that deserves evaluation in the ongoing effort to curb antibiotic resistance. In particular, clinicians’ decisions to administer prophylactic antibiotics to patients with lower respiratory tract infections should be evidence based, to avoid exposing patients to poten­tially unnecessary antibiotics. Although often used in patients with aspiration pneumonitis, antibiotic prophylaxis has not been shown to prevent development of aspiration pneumonia or reduce mortality.⁵ However, data show that more than three-fourths of critical care physicians continue to routinely prescribe antibiotics for patients who have experienced an aspiration event but who do not have an associated infection.⁶

Although pneumonitis and pneumonia are both poten­tial sequelae of aspiration, they are different clinical syndromes. Aspiration pneumonitis represents an acute chemical-induced injury that results when reflux and inhalation of harmful fluids—most typically, sterile acidic stomach contents—cause acute inflammation in the lung. In contrast, aspiration pneumonia represents an acute lung infection that results from aspiration of a large volume of colonized oropharyngeal material.⁷

In a recent study in patients with acute aspiration pneumonitis, Jerome A. Leis, MD, MSc, of the University of Toronto, Ontario, Canada, and colleagues showed that giving prophylactic antibiotics within 48 hours of an aspi­ration event does not provide mortality benefit. Instead, this practice leads to more frequent antibiotic escalation and fewer antibiotic-free days among those patients who do go on to develop aspiration pneumonia.⁵

Dr. Leis and colleagues performed a retrospective cohort study of 200 patients with acute aspiration pneumonitis to investigate the harms and benefits of prescribing anti­biotics in these cases. They examined the patients’ clin­ical outcomes, comparing the findings among those who received prophylactic antibiotics during the first 2 days after an acute macroaspiration event, with those among patients who received standard supportive care.⁵

Of the 200 patients, 76 (38%) received prophylactic anti&shy;biotics and 124 (62%) received only supportive care. The investigators found that unadjusted in-hospital mortality was similar in both groups of patients (25% vs 25%). However, although patients receiving prophylactic antibiotics were not less likely than those receiving standard care to be transferred to critical care (5% vs 6%; P = .7), they had fewer antibiotic-free days (7.5 vs 10.9; P <.0001) and more frequently required their antimicrobial agent to be switched to a new one with a higher spectrum level (8% vs 1%; P = .002) up to 2 weeks after the aspiration event.⁵

Even when the investigators adjusted their analysis to account for patient characteristics that predicted 30-day mortality (eg, age, being admitted to the medicine service rather than to surgery), antibiotic prophylaxis still did not provide mortality benefit (odds ratio, 0.9; 95% CI, 0.4-1.7; P = .7).⁵

Overall, this study highlighted the lack of clinical benefit provided by antibiotic prophylaxis in patients with acute aspiration pneumonitis. It also showed that this practice may even create selective pressures that result in the later need to give more antibiotics—often agents with a broader spectrum of activity&mdash;to those patients who go on to develop aspiration pneumonia.⁵

Therefore, standard supportive care should “remain the mainstay of management of patients with acute aspiration pneumonitis following a macroaspiration event,” Dr. Leis and colleagues said.⁵

THE ROLE OF THE CLINICAL MICROBIOLOGY LABORATORY IN AMS

In another recent study, Dr. Musgrove and colleagues explained that the challenge of antibiotic prescribing for lower respiratory tract infections has been compounded by health care—associated pneumonia criteria defined in the 2005 Infectious Diseases Society of America and American Thoracic Society pneumonia guidelines. “These health care–associated pneumonia criteria had an unintended consequence of excessive use and continu&shy;ation of empiric antibiotics targeting methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aerugi&shy;nosa,” the authors wrote.⁴

Because microbiology results play a critical role in guiding clinicians’ antimicrobial prescribing practices, the authors stressed that clinical microbiology laboratories can thus also contribute to antimicrobial stewardship efforts.⁴

“The language of microbiology results has previously been demonstrated to influence prescriber behavior,” Dr. Musgrove and colleagues said. “Some of these changes can be implemented with few additional resources.” Such simple interventions that change clinicians’ prescribing behavior in a way that guides them to select more appropriate antimicrobial therapy are often described as nudges.⁴

With this in mind, Dr. Musgrove and colleagues performed a quasi-experimental study to investigate the effect of introducing a change in microbiology reporting on respiratory cultures growing commensal flora. They imple&shy;mented this reporting change in May 2016, after which time reports for these respiratory cultures specified “commensal respiratory flora only: No S aureus/MRSA or P aeruginosa.”⁴

The investigators evaluated data from 105 patients during a 6-month period before the intervention was introduced (preintervention group) and from an additional 105 patients during a corre&shy;sponding 6-month period after it was introduced (interven&shy;tion group).⁴

They found that including this simple comment to more clearly communicate respiratory culture results for normal flora positively affected clinicians’ prescribing practices. Clinicians more commonly de-escalated/discontinued use of unnecessary broad-spectrum antibiotics for patients in the intervention group than for those in the preinter&shy;vention group (73% vs 39%, P <.001). “[T]he intervention comment was associated with a 5.5-fold increased odds of deescalation,” the authors wrote. Post intervention, clini&shy;cians also reduced their prescribing of anti-MRSA and antipseudomonal therapy from a median of 7 days to 5 days (P <.001).⁴

Also, fewer patients in the intervention group experienced acute kidney injury (31% vs 14%, P = .003). However, intro&shy;ducing the intervention did not result in any significant difference in all-cause mortality (30% vs 18%, P = .052).⁴

“Stewardship interventions don’t have to be complicated to change behavior,” said Dr. Davis. “This was a simple change to highlight the meaning of the phrase commensal flora, which not everyone understood previously.”

“This intervention helps demonstrate the profound importance of clinical microbiologists in antimicrobial stewardship. Working with them to clearly communicate test results and interpretation can make a big impact on patient care and antibiotic prescribing,” she said.

Because improper antibiotic use can have unintended consequences, the results of these 2 studies in patients with lower respiratory tract infections highlight the importance of appropriate antimicrobial stewardship, including a collaborative approach at all levels of patient care, in tackling this major public health issue.

Dr. Parry, a board-certified veterinary pathologist, graduated from the University of Liverpool in 1997. After 13 years in academia, she founded Midwest Veterinary Pathology, LLC, where she now works as a private consultant. Dr. Parry writes regularly for veterinary organizations and publications.

References

1. Centers for Disease Control and Prevention. Antibiotic/antimicrobial resistance. CDC website. cdc.gov/drugresistance/index.html. Published August 18, 2017. Updated March 29, 2018. Accessed September 4, 2018.
2. Ventola CL. The antibiotic resistance crisis: part 2: management strategies and new agents. P T. 2015;40(5):344-35
3. Malosh RE, Martin ET, Ortiz JR, Monto AS. The risk of lower respiratory tract infection following influenza virus infection: a systematic and narrative review. Vaccine. 2018;36(1):141-147. doi: 10.1016/j.vaccine.2017.11.018.
4. Musgrove MA, Kenney RM, Kendall RE, et al. Microbiology comment nudge improves pneumonia prescribing. Open Forum Infect Dis. 2018;5(7):ofy162. doi: 10.1093/ofid/ofy162.
5. Dragan V, Wei L, Elligsen M, Kiss A, Walker SAN, Leis JA. Prophylactic antimicrobial therapy for acute aspiration pneumonitis [published online February 9, 2018]. Clin Infect Dis. doi: 10.1093/cid/ciy120.
6. Rebuck JA, Rasmussen JR, Olsen KM. Clinical aspiration-related practice patterns in the intensive care unit: a physician survey. Crit Care Med. 2001;29(12):2239-2244.
7. Son YG, Shin J, Ryu HG. Pneumonitis and pneumonia after aspiration. J Dent Anesth Pain Med. 2017;17(1):1-12. doi: 10.17245/jdapm.20117.1.1.