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Interview Questions on Interprofessional Collaboration

1. How can the pharmacist help physicians and other providers in the clinical-decision making process regarding antimicrobial therapy management?
2. In what ways does the pharmacist’s approach to antimicrobial therapy management complement the physician’s?

Introduction Interview: Interprofessional practices when managing antimicrobial therapy  Click here to Show/Hide Audio.

Infections caused by drug-resistant Gram-negative bacteria (GNB) are a growing epidemic causing substantial morbidity and mortality around the United States (US) and globally. Every year in the US, there are at least 2 million drug-resistant infections and at least 23,000 deaths. In 2013, the Centers for Disease Control and Prevention (CDC) published a report, Antibiotic Resistance Threats in the United States, listing and categorizing various types of drug-resistant pathogens. (CDC 2013) Among 18 antibiotic resistance threats listed, many include GNB such as carbapenem-resistant Enterobacteriaceae (CRE), extended spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae (ESBL-E), and multidrug- resistant (MDR) Pseudomonas aeruginosa (MDR-Pa). These three types of drug-resistant infections are among the more common and most devastating infections observed, particularly as hospital-acquired infections, and represent an important area where education for the members of the care team—including pharmacists—is needed.

Epidemiology and Burden of Disease

Resistance among Enterobacteriaceae (i.e. Escherichia coli and Klebsiella spp.) has been increasing over both time (Figure 1 and 2) and space across the US with Klebsiella pneumoniae carbapenemase (KPC)-producing CRE found in all states in the US except one as of August 2017. (CDC 2017) Treatment options for these resistant organisms are limited and lead to significant excess morbidity and mortality. Estimates by the CDC demonstrate that ESBL-E and CRE combine to cause approximately 35,000 infections per year and over 2,000 deaths per year in the US. (CDC 2013) Infections caused by ESBL-E and CRE include urinary tract infections (UTI), pneumonia, intra-abdominal infections, skin and soft tissue infections (e.g. surgical-site infections or diabetic foot infections), and bloodstream infections. Patients with ESBL-E bloodstream infections are more than 50% more likely to die than patients with infections caused by non-ESBL-E bacterial strains. (CDC 2013)

MDR-Pa is designated by the CDC as a ‘Serious Threat Level’ organism that requires “prompt and sustained action” to combat this threat. (CDC 2013) Both susceptible and MDR strains of Pseudomonas aeruginosa cause healthcare-associated infections similar to those caused by ESBL-E and CRE (pneumonia, UTI, surgical-site infections, and bloodstream infections). In the US, P. aeruginosa causes over 50,000 infections per year with approximately 13% caused by MDR-Pa. (CDC 2013) Data from other sources such as the National Healthcare Safety Network (NHSN) report prevalence of MDR strains among P. aeruginosa as high as 22% in 2007. (Kallen 2010) P. aeruginosa is intrinsically resistant to commonly used antibiotics with MDR further limiting treatment options.

Treatment for serious ESBL-E infections generally involves use of carbapenems. Some emerging evidence suggests that beta-lactam/beta-lactamase inhibitors such as piperacillin-tazobactam may also be a reasonable option in some cases. (Vardakas 2012) As more carbapenems are used to treat ESBL-E infections, a rise in CRE infections can be predicted. These highly resistant infections have historically relied on less effective, more toxic second-line agents such as aminoglycosides, tigecycline, and polymyxins. (Narayanan 2016) Notably, newer agents with activity against KPC-producing CRE, such as ceftazidime/avibactam and meropenem/vaborbactam, have made it to market and are gaining experience and evidence as first-line treatment for CRE. (van Duin 2016, Zhanel 2018) Therapeutic options for MDR-Pa continue to be limited and are typically determined by in vitro antibiotic susceptibility testing. Depending on local susceptibility patterns, the options can vary but may include anti-pseudomonal beta-lactams, aminoglycosides, fluoroquinolones, or polymyxins. Newer agents with activity against MDR-Pa include ceftolozane/tazobactam and ceftazidime/avibactam. (van Duin 2016)

The development of novel antibiotics had been inadequate as seen by the steadily decreasing number of new antibiotic approvals by the FDA over the last few decades (Figure 3). (Boucher 2013) However since 2013 there have been 10 new antibiotics approved in the US with 5 specifically active against MDR GNB – ceftolozane/tazobactam, ceftazidime/avibactam, meropenem/vaborbactam, eravacycline, and plazomicin. (CenterWatch). These agents are much needed additions to the antibiotic armamentarium for the global fight against antibiotic-resistant infections. Understanding the pharmacology, anti-bacterial spectrum of activity, and clinical utility of these new antibiotics will be important for members of the care team, both new or experienced, to ensure they are appropriately prescribed for the patients most in need.

With new advances and emerging treatment options, pharmacists play an essential role in the management of infections caused by MDR GNB and can have a positive impact by optimizing patient outcomes while also adhering to antimicrobial stewardship principles and practices. Although pharmacists play a key role on the healthcare team for treating MDR infections, gaps in knowledge and practice involving current and emerging therapies may need to be addressed to optimize their potential in this therapeutic area.

DEFINING DRUG RESISTANCE

Drug resistance among GNB is of particular concern given the various resistance genes they harbor and can pass on and the resulting phenotypic mechanisms of resistance against many antibiotics we consider first-line therapy (Table 1). (Peleg 2010) GNB can both upregulate (chromosomally-mediated) and acquire (plasmid-mediated) these resistance genes. Among these many resistance mechanisms, beta-lactamases are the most common and highly concerning. As discussed earlier, ESBL and KPC production by GNB such as E. coli and Klebsiella spp. confers high-level resistance to most (and sometimes all) beta-lactam antibiotics including last line agents such as carbapenems (i.e. CRE) or polymyxins. MDR-Pa also has the ability to produce beta-lactamases along with other mechanisms such as porin loss and efflux pumps that confer resistance to multiple antibiotic drug classes. These mechanisms, especially in critically ill patients, pose a grave threat to achieving favorable clinical outcomes given the need for inferior antibiotic therapy or lack of effective active antibiotics altogether.

CASE 1 An 81-year-old male, living in a long-term care facility, with a history of benign prostatic hyperplasia, chronic kidney disease, indwelling catheter and recurrent urinary tract infections, is brought to the emergency department with fever and dysuria. On exam he is hemodynamically stable and has suprapubic tenderness. There is no costovertebral angle tenderness. Urinalysis shows a white blood cell count of 80 and is positive for nitrites and leukocyte esterase. Our patient is started on oral ciprofloxacin, which he has been treated with multiple times in the past year. He continues to have fever and dysuria 24 hours later. Urine culture is positive for Klebsiella pneumoniae. While susceptibilities are pending, what antibiotic would you start empirically? What details of the patient’s history are most relevant? What information about the breakpoints used by your microbiology lab would be important to know for antibiotic selection? What resistance mechanism is likely if the Klebsiella pneumoniae is resistant to early generation beta-lactams such as ampicillin, ampicillin-sulbactam, cefazolin, as well as aztreonam, ceftriaxone, and ceftazidime but maintains susceptibility to meropenem? Pause and reflect: Assess this case based on the activity content thus far, then listen to faculty commentary Case 1: Questions and Answers  Click here to Show/Hide Audio.

CURRENT ANTIBIOTIC TREATMENT OPTIONS FOR MDR GNB

Antibiotic treatment for drug-resistant GNB vary based on the resistance mechanism. As such, there may be some overlap of treatment options, but the approach generally differs when treating infections caused by ESBL-E, CRE, or MDR-Pa. Overall, treatment options include beta-lactam antibiotics (e.g. carbapenems or piperacillin/tazobactam), polymyxins (colistin and polymyxin B), tigecycline, aminoglycosides, fosfomycin, and combination antibiotic therapy. We will focus on the former two antibiotic classes in this section given they function as the most common drug class (e.g. for ESBL-E) or last-line resort (e.g. for CRE). The limited number of effective options underlies the need for new and better therapeutic options for treatment of MDR GNB – recently approved options will be discussed in the next section.

Beta-Lactams

Carbapenems are generally considered the treatment of choice for serious infections caused by ESBL-E. For years this has been based on clinical evidence, made up of non-randomized studies, that demonstrate a lower relative risk of mortality for carbapenems in comparison to alternative antibiotics (non-beta-lactam/beta-lactamase inhibitors [BL/BLI]) for treatment of ESBL-E bacteremia. (Vardakas 2012) There are some data that support the use of BL/BLI such as piperacillin/tazobactam for treatment of ESBL-E bacteremia with similar outcomes to carbapenems. (Rodriguez-Bano 2012, Gutierrez-Gutierrez 2016) In 2015, a retrospective cohort study published from Johns Hopkins observed inferiority of empiric piperacillin/tazobactam for treatment of ESBL-E bacteremia when compared to empiric carbapenem therapy. (Tamma 2015) As debate continues on the utility of BL/BLI (specifically piperacillin/tazobactam in the United States) versus carbapenems for serious ESBL-E infections, consideration should be given to the site of infection or source of bacteremia, in vitro susceptibility testing, and severity of illness. Lower severity bloodstream infections with urinary or biliary sources amendable to proper source control may be appropriate scenarios to implement carbapenem-sparing treatment options such as BL/BLIs (i.e. piperacillin/tazobactam).

Recently, the highly anticipated MERINO trial (randomized clinical trial of piperacillin/tazobactam versus meropenem for treatment of ceftriaxone-resistant E. coli or Klebsiella pneumoniae bloodstream infections) has been published providing high-quality evidence to address this debate. (Harris 2018) The investigators of this international study aimed to assess if definitive therapy with piperacillin-tazobactam is noninferior to meropenem. The results demonstrated that piperacillin/tazobactam as definitive therapy for presumptive ESBL-producing E. coli or Klebsiella pneumoniae (ceftriaxone resistant) bloodstream infection was not noninferior to meropenem in 30-day mortality. This trial generally reiterates carbapenems as the drug of choice and now more so than ever these data argue against the use of piperacillin/tazobactam for severe infections. 

Given the variable susceptibility of MDR-Pa, the treatment must be individualized and based on in vitro susceptibility testing. Anti-pseudomonal beta-lactams that may be active versus MDR-Pa and pose a viable option include carbapenems (except ertapenem), ceftazidime, cefepime, aztreonam, and piperacillin/tazobactam. There are no compelling data that one agent is superior to the others. Therefore, selection of beta-lactam for empiric therapy should be based on local antibiograms and for definitive therapy based on isolate-specific susceptibility testing.

Polymyxins

The emergence of MDR organisms has led to the reemergence of an older class of antibiotics— polymyxins. Colistin and polymyxin B are the two agents used clinically. They have broad-spectrum bactericidal activity against Gram-negative aerobic bacilli. This class is one of the last-line therapeutic options for MDR GNB, including Acinetobacter species, P aeruginosa, and CRE particularly with pan-drug resistance against beta-lactam antibiotics. Nephrotoxicity and neurotoxicity are the major limitations that preclude its widespread use. There are differences that are clinically important when deciding on systemic use of colistin versus polymyxin B (Table 2). Although there is more experience with colistin, polymyxin B seems to have a more favorable pharmacokinetic and safety (i.e. nephrotoxicity) profile. (Kassamali 2015) Colistin may be more useful for UTIs or urosepsis over polymyxin B. Despite the availability of newly approved antibiotics, the utility of polymyxins may continue to increase in parallel to the incidence of MDR organisms in the US and worldwide.

CASE 2 As a follow up to CASE 1, would your choice of empiric antibiotic change if the patient above became hypotensive not responsive to intravenous fluids, and was transferred to the intensive care unit? Blood cultures are positive for lactose positive Gram-negative rods. The Klebsiella pneumoniae in the urine culture is resistant to aztreonam, all cephalosporins and quinolones but susceptible to piperacillin-tazobactam and carbapenems. What is considered the drug of choice in this clinical situation? How does this impact antimicrobial stewardship? What are the implications of recent data for this type of infection? Pause and reflect: Assess this case based on the activity content thus far, then listen to faculty commentary Case 2: Questions and Answers  Click here to Show/Hide Audio.

ANTIBIOTIC TREATMENT ADVANCES

Since late 2014, three new antibiotic agents with broad activity against GNB, including MDR strains, have received FDA approval: ceftolozane/tazobactam, ceftazidime/avibactam, and meropenem/vaborbactam. In 2018, the FDA approved two additional antibiotics that can be used for infections caused by MDR GNB: eravacycline and plazomicin. These agents add valuable choices for the treatment of MDR GNB.

Ceftolozane/tazobactam is a novel cephalosporin/BLI combination FDA approved in December 2014. Its anti-bacterial spectrum of activity encompasses Streptococcus spp., various Enterobacteriaceae (including ESBL-E and AmpC beta-lactamase producers), and P. aeruginosa (including MDR strains). It has two currently approved indications including complicated intra-abdominal infections and complicated UTI (including pyelonephritis). (Zerbaxa PI) In a phase 3 randomized controlled trial (RCT) assessing ceftolozane/tazobactam versus levofloxacin for UTI, ceftolozane/tazobactam proved superior for microbiologic and clinical cure. (Wagenlehner 2015) In a phase 3 RCT evaluating efficacy against meropenem for intra-abdominal infections, ceftolozane/tazobactam was non-inferior to meropenem, including drug-resistant Gram-negative strains. (Solomkin 2015) Both phase 3 RCTs included strains of ESBL-E which offers useful insight to treatment of resistant infections. In vitro studies of ceftolozane/tazobactam activity against resistant strains of P. aeruginosa are compelling. In one study of P. aeruginosa clinical isolates from US hospitals, 84% of MDR isolates and 77% of extensively-drug resistant isolates were susceptible to ceftolozane/tazobactam while meropenem was 23% and 12% susceptible, respectively. (Shortridge 2017) The RCT data in addition to knowledge of its in vitro activity makes ceftolozane/tazobactam a clinically useful option for treatment of MDR-Pa infections and even as a potential carbapenem-sparing regimen for ESBL-E infections.

Ceftazidime/avibactam is a cephalosporin/novel BLI combination FDA approved in February 2015. It has potent broad-spectrum activity against various GNB including drug-resistant strains such as ESBL-E, CRE (KPC-producers), AmpC-producing GNB, and MDR-Pa. Indications include complicated UTIs (including pyelonephritis), complicated intra-abdominal infections, and now hospital-acquired and ventilator- associated pneumonia (HAP/VAP). (Avycaz PI) Notably, an RCT was done that evaluated ceftazidime/avibactam versus best-available therapy (mostly carbapenem monotherapy) for treatment of ceftazidime-resistant infections (mostly complicated UTI). Ceftazidime/avibactam had a similar rate of clinical cure to meropenem which provides high-quality evidence for the treatment of drug-resistant infections. (Carmeli 2016) A retrospective cohort study conducted by Shields and colleagues demonstrated the superiority of ceftazidime/avibactam versus other antibiotic therapy for CRE (specifically Klebsiella pneumoniae) bacteremia. (Shields 2017) Most recently, a prospective, multicenter, observational study was conducted by the Antibacterial Resistance Leadership Group evaluating colistin versus ceftazidime/avibactam for treatment of CRE infections. The most common site of infection was the bloodstream (46%). All-cause 30-day hospital mortality was significantly lower for ceftazidime/avibactam as compared to colistin (9% versus 32%, p=0.001). (van Duin 2018) Ceftazidime/avibactam provides a much-needed treatment option for CRE and MDR-Pa infections.

Meropenem/vaborbactam is an anti-pseudomonal carbapenem/novel BLI combination approved by the FDA in August 2017. Vaborbactam protects meropenem from degradation by certain beta-lactamases, most importantly KPC, and adds to the already broad-spectrum Gram-negative activity of meropenem. Unfortunately, meropenem/vaborbactam offers little advantage over meropenem alone against MDR isolates of P. aeruginosa. (Nguyen 2018) This latest antibiotic is FDA approved for the treatment of complicated UTI (including pyelonephritis). It was evaluated in a phase 3 RCT versus piperacillin/tazobactam and proved to be non-inferior in terms of clinical cure and microbiologic eradication. (Vabomere PI) Another phase 3 RCT (TANGO II) assessing meropenem/vaborbactam versus best available therapy for CRE infections was stopped early due to the risk-benefit consideration (in favor of meropenem/vaborbactam), therefore the decision was made that randomization to best available therapy should cease. In TANGO II, meropenem/vaborbactam was associated with decreased mortality, increased clinical cure, and lower rates of nephrotoxicity compared to best available therapy for CRE infections. (Wunderink 2018) As more experience and evidence accumulates for meropenem/vaborbactam, its utility will also increase, and we now have another effective option for the treatment of KPC-producing CRE infections.

CASE 3 A 64-year-old woman, with chronic obstructive pulmonary disease, on chronic steroids and home O2, is admitted with fever, cough and respiratory distress. Her chest X-ray shows a right lower lobe consolidation. She is intubated and started on piperacillin-tazobactam and vancomycin but continues to have fever, high oxygenation requirements, and significant purulent secretions. Respiratory culture is growing lactose negative Gram-negative rods. What are this patient’s risk factors for MDR Pseudomonas infection? Susceptibility testing for which antibiotics should be requested from the microbiology lab? What would be good empiric antibiotic choices? Pause and reflect: Assess this case based on the activity content thus far, then listen to faculty commentary Case 3: Questions and Answers  Click here to Show/Hide Audio.

Eravacycline is a synthetic tetracycline antibiotic approved by the FDA in August 2018 for the treatment of complicated intra-abdominal infection (cIAI). (Xerava PI) Like other tetracyclines, it inhibits protein synthesis by binding to the 30S ribosomal subunit but is not significantly affected by efflux pumps or other tetracycline-specific resistance mechanisms. Eravacycline, like tigecycline, is active against most Gram-negative bacteria, including some extended-spectrum beta lactamase producing organisms, some Gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE), and many anaerobes. One important exception to this broad spectrum of activity is Pseudomonas. However, eravacycline has demonstrated activity against some carbapenem-resistant strains of Gram-negative bacteria, creating interest in its potential to treat infections caused by CRE. Particularly notable is that antimicrobial susceptibility testing indicates that eravacycline is more effective against carbapenem-resistant Acinetobacter baumannii than comparable tetracyclines, levofloxacin, amikacin, tobramycin, and colistin. (Seifert 2018) While clinical data is limited, these data are promising, particularly given the limited options for infections caused by MDR Acinetobacter.

Two global, multi-center, double-blind, phase 3 studies studied eravacycline for treatment of cIAI. In IGNITE1 (Investigating Gram-Negative Infections Treated with Eravacycline), eravacycline demonstrated non-inferiority compared to ertapenem for treatment of cIAI. (Solomkin 2017) InIGNITE4, eravacycline was non-inferior to meropenem in clinical outcome of cIAI 28 days after randomization. (Newman 2018) Interestingly, the IGNITE2 phase 3 clinical trial found that eravacycline administered as an intravenous (IV) to oral transition therapy for the treatment of complicated urinary tract infections (cUTI) did not achieve its primary endpoint of statistical non-inferiority compared to levofloxacin. (Tsai 2016) As a result, eravacycline has not been approved for this indication, and is only approved in its IV formulation.

With less than 5% of patients experiencing gastrointestinal intolerance with eravacycline, the lower incidence of gastrointestinal side effects with eravacycline compared to tigecycline adds to its potential utility. But as with many of the other newly approved antibiotics, use of eravacycline should be reserved for suspected or confirmed drug-resistant bacteria. (Xerava PI)

Plazomicin is a once-daily aminoglycoside antibiotic which was engineered to overcome aminoglycoside-modifying enzymes, the most common aminoglycoside-resistance mechanism in Enterobacteriaceae. It has a relatively narrow spectrum of activity which includes several Gram-negative bacteria (e.g., E. coli, K. pneumoniae, Proteus, Enterobacter species) as well as Staphylococcus aureus, including MRSA, but has limited activity versus most P. aeruginosa and Acinetobacter baumannii isolates and lacks activity against Enterococcus species, as well as Streptococcus species, Stenotrophamonas maltophilia, and obligate anaerobes. It has demonstrated in vitro activity against ESBL-producing, aminoglycoside-resistant, and carbapenem-resistant isolates. (Zemdri PI) Plazomicin was approved by the FDA in June 2018 for the treatment of complicated urinary tract infections based on the results of the phase 3 EPIC (Evaluating Plazomicin In cUTI) trial, which demonstrated the non-inferiority of plazomicin compared to meropenem for treatment of cUTIs, including pyelonephritis. (Cloutier 2017)

While potential side effects of plazomicin include headache, nausea, vomiting and diarrhea, the most concerning are similar to those of other aminoglycosides, resulting in boxed warnings regarding nephrotoxicity, ototoxicity, neuromuscular blockade, and fetal harm in pregnant mothers. Plazomicin is eliminated primarily by renal mechanisms and requires dose adjustment for impaired renal function. Monitoring baseline and daily creatinine clearance is recommended with use of plazomicin and therapeutic drug monitoring (TDM) is recommended in patients with a creatinine clearance of less than 90 mL/min. Most of the time, increases in creatinine clearance have been minimal and reversible. However, the risk of serious nephrotoxicity is increased in patients with preexisting renal impairment, the elderly, and those on concomitant nephrotoxic agents so plazomicin should be used with particular caution in these populations. Aminoglycoside-associated ototoxicity may be irreversible, and risk is higher in patients with preexisting renal impairment, family history of hearing loss or on prolonged high doses. Neuromuscular blockade typically only occurs in patients with underlying neuromuscular blockade disorders or receiving neuromuscular blocking agents.

While these risks place limitations on the usefulness of plazomicin, it provides an alternative antibiotic for treatment of cUTIs caused by MDR GNB. Over 99% of E. coli, Klebsiella pneumoniae and Enterobacter cloacae in U.S. surveillance are susceptible to plazomicin when applying the FDA-approved breakpoint of ≤ 2 mcg/mL. (Zemdri PI)

CASE 4 A 72-year-old male, with a history of type 2 diabetes mellitus and renal transplant, presents with fever, abdominal pain and jaundice. A month ago, he traveled to India to visit family and was hospitalized with kidney stones and underwent lithotripsy. His family reports he had an indwelling catheter placed temporarily and received a broad-spectrum cephalosporin at the time. What are this patient’s risk factors for CRE infection? If susceptibility results are consistent with CRE, what additional antibiotic susceptibility testing should be requested from the microbiology lab? What would be a good empiric antibiotic choice? Pause and reflect: Assess this case based on the activity content thus far, then listen to faculty commentary Case 4: Questions and Answers  Click here to Show/Hide Audio.

All the discussed newly approved antibiotics provide much needed options to the therapeutic arsenal against MDR GNB. Caution should still be exercised despite the potency and high susceptibility rates for these new agents. Resistance will continue to emerge which require all treating clinicians to indefinitely utilize antimicrobial stewardship principles and practices to preserve the usefulness of both old and new antibiotics. For instance, reports of treatment of CRE infections with ceftazidime/avibactam which led to recurrent CRE infections and microbiologic failure are concerning. Most alarmingly, ceftazidime/avibactam resistance emerged in a substantial proportion of those with microbiological failure. (Shields 2016) This emphasizes the importance of using antibiotics judiciously to prevent emergence of resistance. 

CLINICAL PRACTICE GAP AND THE ROLES OF THE PHARMACIST AND INFECTIOUS DISEASES PHYSICIAN IN MANAGEMENT OF MDR GNB INFECTIONS

Despite the availability of active antibiotics for most cases of infections caused by MDR GNB, the options are limited or relatively ineffective and require optimal utilization to maximize clinical outcomes (e.g. proper antibiotic selection, appropriate dosing, etc.). Pharmacists and infectious diseases (ID) physicians in the hospital setting are on the frontlines of clinical care and management of antibiotic therapies and are uniquely positioned to work with other members of the healthcare team to ensure optimal utilization of antibiotics in the management of MDR GNB infections.

Whether a pharmacist is ID-trained rounding with an ID consult service, a general clinical pharmacist rounding with a general medicine team, or a staff pharmacist verifying orders for a particular unit, each has a key role in knowing the optimal therapy for treating MDR GNB. Pharmacists are readily consulted by physicians, nurse practitioners, physician assistants, or other clinicians to gain knowledge about appropriate drug selection and dosing. There is a unique opportunity on a case-by-case basis to instill knowledge in healthcare providers for the management of MDR GNB infections. In order to do so, pharmacists need the proper up-to-date education, including knowledge of the previously discussed new antibiotic agents effective against MDR GNB.

Pharmacists have a major role in management of antimicrobial stewardship programs. (Barlam 2016) Antimicrobial stewardship in hospitals around the country will become increasingly important as antimicrobial resistance grows and new antibiotic agents come to market. As presented by the CDC’s Core Elements of Hospital Antibiotic Stewardship Programs, a pharmacist leader is listed as an essential component along with an ID physician leader. (CDC 2014) While one pharmacist may lead the efforts of an antimicrobial stewardship program, pharmacists throughout the hospital are key personnel in carrying out the daily designated duties and cognitive functions. Two core components of an antimicrobial stewardship program include preauthorization and/or prospective audit and feedback. Both are areas in which every pharmacist can impact the success of a stewardship program, especially when monitoring the use of newer antibiotic agents. Other key pharmacist-led duties include but are not limited to routine education for medical teams and development of clinical guidelines/protocols to systematically improve antibiotic utilization. (Barlam 2016) Lastly, pharmacists have an important role on a hospital’s Pharmacy and Therapeutics Committee where decisions are made about formulary additions. A pharmacist’s knowledge about new and emerging antibiotics can prove to be valuable when making decisions about adding new antibiotics to the hospital formulary. Pharmacists need further education to understand these new antibiotics and the MDR GNB infections they treat in order to fulfill their potential as comprehensive medical team members.

The information provided by well-informed pharmacists can be very helpful to ID physicians. While ID specialists possess a higher level of knowledge about antimicrobials than non-ID physicians, they also more frequently encounter patients with challenging infections, including those caused by MDR organisms. Previous studies have demonstrated a mortality benefit when ID specialists are consulted in cases involving MDR bacteria. (Tissot 2014, Burnham 2018) However, as discussed above, the limitations of current antibiotic options for MDR GNB infections means the ID physician needs to make a more nuanced, complicated assessment of risks versus benefits, monitor more closely for drug toxicities, and consider antibiotic combinations, often in the absence of high-quality data. In these situations, team-based management, in particular close collaboration between pharmacist and physician, can be key to providing a patient with the best possible care. This same collaboration and dual leadership form the foundation of a successful antimicrobial stewardship program, since active interventions such as preauthorization, auditing and feedback, have been found to be more effective than passive interventions such as educational materials. (Barlam 2016) Pharmacists and ID physicians can take a “divide and conquer” approach to these more time-consuming active interventions, and find continued common ground in their goal to provide patients with carefully-selected antibiotics designed to treat the patient successfully, without contributing to the alarming rise in MDR infections. 

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