Safety of De-Escalating Empiric Antimicrobial Agents in Trauma Patients with Indigenous Oral Flora Ventilator-Associated Pneumonia

Abstract

Background:

Ventilator-associated pneumonia (VAP) is a frequently occurring nosocomial infection in critically ill trauma patients. When bronchoalveolar lavage (BAL) returns with indigenous oral flora (IOF), de-escalating antimicrobial therapy is challenging.

Patients and Methods:

This is a retrospective review of trauma patients who received broad-spectrum empiric antimicrobial therapy for clinical VAP, and whose BAL culture resulted with >100,000 CFU/mL of IOF from September 1, 2017 to September 1, 2020. Patients were identified using the trauma database and microbiology reports of BALs with IOF. This review evaluated the effect of antibiotic de-escalation on recurrent or persistent pneumonia.

Results:

Of 51 trauma patients with clinical VAP and IOF, 18 patients (35.3%) had antimicrobial agents de-escalated. De-escalation was driven primarily by the discontinuation of vancomycin, with the continuation of a β-lactam antibiotic as monotherapy for the remainder of the treatment course (n = 15; 86.7%). The overall rate of either persistent or recurrent VAP in the cohort was 10%, and this did not differ statistically between those who received de-escalation therapy after isolation of IOF and those who did not (16.7% vs. 6.1%; p = 0.224), however, the incidence of acute kidney injury (AKI) was higher in the non-de-escalation group (39.4% vs. 11.1%; p = 0.034). There was no statistical difference in ventilator days, intensive care unit (ICU) length of stay, or hospital length of stay between treatment groups.

Conclusions:

Trauma patients who develop VAP with isolated BAL cultures of IOF or mixed flora can safely have anti-methicilllin-resistant Staphylococcus aureus (MRSA) antimicrobial agents discontinued, and this may result in decreased rates of AKI.

Ventilator-associated pneumonia (VAP) is a frequently occurring nosocomial infection associated with substantial morbidity in critically ill patients.^1-4 Trauma patients have both earlier development of and higher incidences of VAP compared with critically ill non-trauma patients.⁵ For treatment of VAP, the Infectious Diseases Society of America (IDSA) recommends empiric antimicrobial agents targeting Pseudomonas aeruginosa and, in certain at-risk patients, methicillin-resistant Staphylococcus aureus (MRSA).⁶ De-escalation of antimicrobial agents based on microbiologic culture data is recommended, is a cornerstone of antimicrobial stewardship, and is linked to cost savings and decreases in resistant pathogens.⁶ To facilitate monitoring for appropriate treatment, microbiologic samples are typically collected prior to initiation of empiric antimicrobial therapy. Bronchoalveolar lavage (BAL) is commonly used in trauma patients to confirm the clinical diagnosis of VAP and to guide pathogen-directed therapy.⁵

Occasionally, BALs will result with growth of mixed collections of various intra-oral organisms, and the result is labeled by the microbiology laboratory as indigenous oral flora (IOF), without identification or work-up of specific organisms. These organisms include a predominance of non-pathogenic organisms such as coagulase-negative staphylococci, diphtheroids, Fusobacterium spp., and viridans streptococci.^7,8 Potential pathogens that can be part of oral flora such as Haemophilus spp., Staphylococcus aureus, and Streptococcus pneumoniae may be reported and worked up by the microbiology laboratory separately from the IOF if those potential pathogens are present in equal or greater quantity than the oral non-pathogens, or if they appear to be associated with the white blood cell count on gram stain. If intra-oral potential pathogens are present but are outnumbered by oral non-pathogens, these organisms may not necessarily be worked up and identified, and could be included under the IOF results.

Current IDSA guidelines do not provide guidance for antimicrobial treatment decisions when a sample grows IOF, and because this microbiologic definition includes both gram-positive and gram-negative organisms, tailoring antimicrobial therapy becomes complex if not impossible.⁸ As a result, treatment decisions are variable.

Continuation of empiric broad-spectrum antimicrobial agents for VAP is not without risk. One common antibiotic combination, vancomycin and piperacillin-tazobactam, has been associated with acute kidney injury (AKI).⁹ However, if used for less than 72 hours and de-escalated as cultures allow, the risk of AKI may be reduced.¹⁰ Furthermore, extended courses of broad-spectrum antimicrobial therapy can lead to Clostridioides difficile infection (CDI) and the emergence of multi-drug–resistant organisms.¹¹ The objective of this study was to determine if trauma patients with BAL results of IOF can safely have empiric anti-MRSA and/or anti-pseudomonas antimicrobial agents de-escalated.

Patients and Methods

This retrospective cohort study was performed at a level 1 trauma center and received exemption determination by the University of Louisville Institutional Review Board. Patients were included if they were admitted to the trauma service between April 1, 2016 and August 31, 2021, had a BAL that grew >100,000 CFU/mL of IOF, and received empiric anti-MRSA and anti-pseudomonas antimicrobial agents. Patients were excluded if they had a prior VAP during admission, died within four days after the BAL was obtained, had empiric antimicrobial agents for VAP started >24 hours before the BAL was obtained, had a BAL with >100,000 CFU/mL of another specific pathogen, were immunosuppressed, had a concomitant infection other than bacteremia prior to or during the VAP, or were transferred after inpatient hospitalization from an outside hospital. Patients were defined as immunosuppressed based on history of autoimmune disorder or the presence of anatomic therapeutic chemic (ATC) class L04 selective immunosuppressants, ATC class L01 antineoplastic agents, or prednisone-equivalent doses >7.5 mg in the medication history.

Demographic, respiratory, microbiologic, and laboratory data were collected via electronic medical record as well as reports generated from the institution's microbiology and trauma databases. Bronchoalveolar lavage was collected in response to clinical signs and symptoms of VAP, including new or worsening radiographic infiltrate, leukocytosis, systemic inflammatory response syndrome (SIRS), or purulent tracheal secretions. Bronchoalveolar lavage was performed by surgical residents or fellows in post-graduate years two to seven under the direction of attending surgical faculty with board certifications in critical care medicine.

Prior to the procedure, patients were sedated and chemically paralyzed at the discretion of the physician performing the procedure. A fiber-optic bronchoscope was advanced through the endotracheal or tracheostomy tube and guided into the airways. After clearing gross secretions bilaterally, the bronchoscope was withdrawn, flushed with saline, and a sterile suction trap was inserted in the suction line. The bronchoscope was navigated to the lung segment of interest and 30–50 mL of saline was instilled and gently suctioned, with return of approximately 50% of the instilled saline to the suction trap. This was sent for gram stain, quantitative culture, and sensitivity.

As described in other studies, antimicrobial agents were ranked according to spectrum of gram-negative activity as follows: rank 5, carbapenem; rank 4, antipseudomonal β-lactam (piperacillin-tazobactam or cefepime); rank 3, third-generation cephalosporin; rank 2, quinolone, ampicillin-sulbactam, or trimethoprim-sulfamethoxazole; rank 1, other β-lactam (cefazolin, ampicillin, penicillin G). By the end of day four of empiric treatment, patients who received either a decrease in total antimicrobial rank (i.e., piperacillin-tazobactam switched to ceftriaxone) or a decrease in the total number of antimicrobial agents (i.e., discontinuation of vancomycin or linezolid) were considered to have had de-escalation therapy.^12-14 Day four of treatment was chosen as it typically takes three days for the microbiology laboratory to finalize culture results from a BAL sample, and an additional day was added to allow time for culture review by the surgical team. Patients who were continued on the same empiric broad-spectrum antibiotic agents beyond day four of initiation were considered to have had non-de-escalation therapy.

The primary outcome was the combined rate of VAP persistence and VAP recurrence. Ventilator-associated pneumonia persistence was defined as having a follow-up BAL culture with >100,000 CFU/mL of organism on or after day four of VAP treatment and before end of treatment. Ventilator-associated pneumonia recurrence was defined as a subsequent BAL culture with >100,000 CFU/mL of organism within 10 days after end of antimicrobial treatment. Secondary outcomes included hospital mortality, AKI, intensive care unit (ICU) length of stay, ventilator support days, and incidents of CDI or multi-drug–resistant organism isolation post-VAP treatment. Acute kidney injury was defined as a change in serum creatinine (SCr) of 1.5 × baseline or an absolute increase by 0.3 mg/dL, which occurred during the period from the day of initiation of antibiotic agents through 72 hours after antibiotic completion.¹⁵

Data were analyzed using Microsoft Excel (Microsoft, Redmond, WA). Continuous variables were assessed utilizing Mann-Whitney U test and categorical variables were assessed using the χ² test or Fisher exact test. A p value <0.05 was considered statistically significant.

Results

During the study period, 125 trauma patients had a BAL that grew >100,000 CFU/mL of IOF. The most common reason for exclusion was having >100,000 CFU/mL of a specific pathogen also present within the BAL, in addition to IOF (n = 52). After applying exclusion criteria, 51 trauma patients with clinical VAP and IOF were included for analysis. The most common empiric antimicrobial agents were vancomycin and piperacillin-tazobactam, with 100% and 47% of patients receiving these, respectively. Of the cohort of 51 patients with IOF VAP, 18 patients (35.3%) had antimicrobial agents de-escalated and 33 patients (64.7%) continued on both broad-spectrum empiric antibiotic agents past day four of treatment. Bronchoalveolar lavages were performed secondary to clinical suspicion of VAP a mean ± standard deviation (SD) of 4.1 ± 2.4 days after intubation.

The groups were similar with no statistical differences in baseline characteristics (Table 1). De-escalation was driven primarily by the discontinuation of vancomycin, with the continuation of the same empiric beta-lactam antibiotic as monotherapy for the remainder of the treatment course (n = 15; 83.3%). Only three patients in the de-escalation group had changes to their gram-negative antimicrobial agents: one patient had both intravenous antimicrobial agents discontinued and changed to oral trimethoprim-sulfamethoxazole, whereas the other two patients had all antimicrobial agents discontinued at day three of therapy. Eight (44.4%) patients in the de-escalation group and 13 (40.6%) in the non-de-escalation group had a repeat BAL performed either during treatment or within 10 days of treatment ending.

Table 1.

Baseline Characteristics

	Non-de-escalation n = 33	De-escalation n = 18	p
Age, y, median (IQR)	51.5 (31.5–61.25)	55 (39–64)	0.575
Gender, male (%)	32 (97)	15 (83)	0.083
Weight, kg, median (IQR)	86 (74.5–101)	85.5 (78.75–104.35)	0.841
Chronic obstructive pulmonary disease, n (%)	5 (15.2)	2 (11.1)	0.637
Diabetes mellitus, n (%)	7 (21.2)	3 (16.7)	0.696
Smoker, n (%)	11 (33.3)	8 (44.4)	0.432
Injury mechanism Blunt, n (%) Penetrating, n (%)	30 (91) 3 (9)	18 (100) 0 (0)	0.544
Rib fractures, n (%)	19 (57.6)	12 (66.7)	0.525
Injury severity score, median (IQR)	27 (17–38)	22 (17.3–32.8)	0.561
Abbreviated injury scale of head, median (IQR)	2 (0–4)	0.5 (0–2.8)	0.258
Spinal cord injury, n (%)	6 (18.2)	1 (5.6)	0.398
Temperature (max) day of BAL, ^°F, median (IQR)	101.9 (100.7–102.4)	101.6 (101.1–102.7)	0.968
White blood cell count on day of BAL, × 10⁹/L, median (IQR)	11.5 (8.2–15.1)	11.1 (9.3–13.1)	0.315
PaO₂/FiO₂ ratio, median (IQR)	166 (126–210)	154.7 (133.6–177.7)	0.818
Intubation to VAP, days, median (IQR)	4 (3–5)	4 (2.25–6.25)	0.960
Baseline serum creatinine, median (IQR)	0.78 (0.69–0.95)	0.91 (0.66–1.01)	0.936
Treatment duration, days, median (IQR)	8 (7–10)	7.5 (4.5–8)	0.373
Day of de-escalation, median (IQR)	—	3 (2–3)	—
Empiric anti-MRSA antimicrobial, N (%) Vancomycin Linezolid	32 (97) 1 (3)	18 (100) 0 (0)	1
Empiric anti-pseudomonal antimicrobial, N (%) Piperacillin-tazobactam Cefepime Meropenem	20 (60.6) 13 (39.4) 0 (0)	13 (72.2) 4 (22.2) 1 (5.6)	0.201
Criteria for de-escalation, n (%) Discontinuation of vancomycin Decrease in gram-negative antimicrobial rank	—	15 (83.3) 3 (16.7)	—

PaO₂ = partial pressure of oxygen; FiO₂ = fraction of inspired oxygen; MRSA = methicillin-resistant Staphylococcus aureus IQR = interquartile range.

The overall rate of either persistent or recurrent VAP in the cohort was 10%, and this did not differ statistically between those who received de-escalation therapy after isolation of IOF and those who did not (16.7% vs. 6.1%; p = 0.224). No incidences of VAP persistence occurred in the de-escalation group compared with one incidence in the non-de-escalation group (Table 2). Two patients in both groups died while in the hospital. Incidence of AKI was higher in the non-de-escalation group (39.4% vs. 11.1%; p = 0.034; Table 3). There was no statistical difference in ventilator days, ICU length of stay, or hospital length of stay between treatment groups. Subsequent recovery of multi-drug–resistant organisms and Clostridioides difficile-associated diarrhea was rare, and rates did not differ between groups.

Table 2.

Secondary Outcomes

	Continuation n = 33	De-escalation n = 18	p
VAP persistence and/or recurrence, n (%)	2 (6.1)	3 (16.7)	0.224
VAP persistence	1 (3.2)	0 (0)	—
VAP recurrence	1 (3.2)	3 (16.7)	—

VAP = ventilator-associated pneumonia.

Table 3.

Secondary Outcomes

	Continuation n = 33	De-escalation n = 18	p
Mortality, n (%)	2 (6.1)	2 (11.1)	0.521
Acute kidney injury, n (%)	13 (39.4)	2 (11.1)	0.034
1.5 × serum creatinine, n (%)	10 (30.3)	1 (5.6)	—
Absolute increase ≥0.3 mg/dL in serum creatinine, n (%)	13 (39.4)	2 (11.1)	—
Ventilator support days, median (IQR)	11 (6.75–19)	12.5 (7.25–17.75)	0.920
ICU length of stay, median (IQR)	16 (8–22)	15.5 (10.5–22)	0.681
Hospital length of stay, median (IQR)	20 (16–31)	19 (16–28)	0.589
Clostridioides difficile, n (%)	1 (3)	0 (0)	1
Multi-drug–resistant organism, n (%)	3 (9.1)	2 (11.1)	0.816

IQR = interquartile range; ICU = intensive care unit.

Discussion

This is the first study to our knowledge to compare outcomes of de-escalating antimicrobial agents in the setting of mixed flora or IOF and VAP. Previous studies found no difference in rates of VAP recurrence or mortality when antimicrobial agents are narrowed based on culture results of targeted pathogens.^16–18 However, the non-specific bacteriologic result of mixed flora or IOF presents a difficult therapeutic challenge. Clinicians may be hesitant to deescalate antimicrobial agents because of concerns that a potential pathogen was missed in sampling or reporting. Additionally, there may be concerns that if antimicrobial agents are stopped prematurely, then organisms potentially present, but in insufficient quantity to be identified, will multiply and predominate. Indeed, absence of a documented etiologic organism has been implicated as a risk factor for inappropriate continuation of vancomycin.¹⁹ Our study found no statistical difference in rates of VAP recurrence or persistence between patients who had antimicrobial de-escalation and patients who had all broad-spectrum empiric antimicrobial agents continued beyond day four.

Patients who continued on both broad-spectrum antibiotic agents had a numerically lower percentage of VAP recurrence or persistence (6.1% vs. 16.7%). It is possible that our study was underpowered to detect a statistical difference. However, of the three patients with recurrent VAP in the de-escalation group, one patient had all antimicrobial agents discontinued, and this patient grew Acinetobacter and Serratia spp. susceptible to piperacillin-tazobactam. This suggests that this patient may have benefitted from having an anti-pseudomonal β-lactam continued for the full recommended seven days of treatment for VAP. The other two patients had head trauma (head Acute Injury Score [AIS] of 3 and 4), which likely placed them at increased risk for VAP.²⁰ Additionally, these two patients only had vancomycin discontinued (continuing therapy on an antipseudomonal β-lactam alone) and did not grow gram-positive organisms in the repeat BAL, suggesting that discontinuing anti-MRSA antimicrobial treatment did not influence the recurrence of VAP.

The overall rate of VAP recurrence or persistence in our cohort was lower than a previously published recurrence rate of 30% observed after treatment of VAP caused by specific isolated bacteria (MRSA, Escherichia coli, etc.) in critically ill surgical patients.¹⁶ This may suggest that growth of >100,000 CFU/mL of indigenous flora may be associated with lower risk of VAP recurrence or persistence than >100,000 CFU/mL of a specific causative organism, or could be due to other institutional or protocol differences.

Repeat bronchoscopy following the initial positive BAL was not uncommon in our cohort, occurring in 44.4% of de-escalated patients and 39.4% of non-deescalated patients. However only 10% of the overall cohort had a positive BAL, categorizing them as VAP persistence or recurrence. Of the five patients in the overall cohort who had VAP persistence or recurrence, four (80%) had BAL samples that grew organisms that retained in vitro susceptibility to the patient's most recent antimicrobial regimen (Table 4). This suggests that other factors outside of antimicrobial selection or discontinuation may have contributed to VAP recurrence or persistence. Importantly, no patients had a repeat BAL sample that grew MRSA in either group.

Table 4.

Patients with VAP Recurrence/Persistence after IOF VAP Treatment

Group	Age (y)	ISS	AIS (head)	Antimicrobials for index IOF VAP	Organism isolated during subsequent VAP	Microbiologic susceptibility
Non-de-escalation	57	38	0	Vancomycin × 11 days Piperacillin-tazobactam x 11 days	Pseudomonas aeruginosa	Susceptible to piperacillin-tazobactam
Non-de-escalation	52	43	5	Vancomycin × 7 days Cefepime × 7 days	Pseudomonas aeruginosa Klebsiella pneumoniae	Susceptible to cefepime
De-escalation	20	21	4	Vancomycin × 4 d Piperacillin-tazobactam × 8 d	MSSA	Susceptible to piperacillin-tazobactam
De-escalation	81	27	0	Vancomycin × 3 d Piperacillin-tazobactam × 3 d	Acinetobacter baumannii Serratia marcescens	Susceptible to piperacillin-tazobactam
De-escalation	81	22	3	Vancomycin × 2 d Piperacillin-tazobactam × 10 d	Klebsiella oxytoca	Intermediate to piperacillin-tazobactam

ISS = Injury Severity Score; AIS = Abbreviated Injury Scale; IOF = indigenous oral flora; VAP = ventilator-associated pneumonia; MSSA = methicillin-susceptible Staphylococcus aureus.

Reported rates of mortality associated with VAP vary widely in the literature.⁶ No statistical difference in mortality was found in our study, and our overall mortality rate was low at 8%. Ventilator-associated pneumonia has been demonstrated to increase ventilator days and length of hospitalization.⁶ Patients in our cohort spent a similar amount of time on mechanical ventilation and in the hospital compared with other cohorts.²¹ De-escalating antimicrobial agents in the setting of VAP with IOF did not impact ventilator days or ICU length of stay.

All patients in our study received guideline-recommended empiric antimicrobial agents. Because >20% of Staphylococcus aureus isolates from our institution are methicillin resistant, patients received either vancomycin or linezolid empirically, in combination with an anti-pseudomonal β-lactam. The most frequent intervention that met criteria for de-escalation therapy was the discontinuation of anti-MRSA antimicrobial agents. It could be reasonable to de-escalate anti-pseudomonal antimicrobial agents in clinically stable patients with IOF isolated from a BAL, however a more specific interpretation of our data would be that these patients may safely have anti-MRSA antimicrobial agents discontinued. This is supported by the fact that no patient in our cohort had a repeat BAL that grew MRSA. Staphylococcus aureus grows rapidly in culture allowing for quick identification.²² Methicilllin-resistant Staphylococcus aureus nares testing has excellent negative predictive values for MRSA in pneumonia.²³ In addition to MRSA nares testing, the growth of mixed flora may be another signal that anti-MRSA antimicrobial agents can be safely discontinued. However, patients in both groups did grow resistant gram-negative organisms such as Pseudomonas aeruginosa and Acinetobacter baumannii in repeat BAL samples.

The most utilized antimicrobial agents for empiric VAP treatment in our cohort was the combination of vancomycin and piperacillin-tazobactam, which has been previously implicated in increased risk of AKI.^9,24 In our study, a higher rate of AKI was observed in the non-de-escalation group. Overall, 15 (29.4%) patients developed an AKI during antimicrobial treatment according to our definition, with 39.4% occurring in the non-de-escalation group compared with 11% occurring in the de-escalation group. We postulate that lower AKI risk may be due to early discontinuation of vancomycin in the de-escalation group. This finding is consistent with previous studies that found no additional risk of AKI when the combination of vancomycin and piperacillin-tazobactam was used for <72 hours.¹⁰ Continued treatment with vancomycin comes with increased financial burden through both direct drug cost as well as therapeutic drug monitoring.^25,26

A major justification for antimicrobial de-escalation is the prevention of antimicrobial resistance.⁶ Additionally, use of multiple classes of antimicrobial agents has been suggested to increase the risk of CDI in surgical patients, specifically.²⁷ In our evaluation, CDI and isolation of multi-drug–resistant organisms was rare, and no difference could be found between groups. This may be explained in part by the fact that patients in the de-escalation group received anti-pseudomonal β-lactams for similar durations as patients in the non-de-escalation group. Overuse of vancomycin has been associated with the development of drug-resistant enterococcus, as well as vancomycin resistance in Staphylococcus aureus.^28,29 Although our study was not powered to detect difference in rate of gram-positive resistance, clinicians should be mindful of the downstream harms associated with continuation of anti-MRSA coverage in the absence of isolated resistant gram-positive organisms.

Only 10% of patients in our cohort had VAP recurrence and/or persistence. Other studies assessing VAP recurrence and/or persistence report rates ranging from 22%–49%.^30–32 The lower event rate in our study could in part be due to having a higher threshold of >100,000 CFU/mL, however, this event rate is still half the rate of another study with the same quantitative definition.³⁰ A meta-analysis evaluating risk factors for VAP recurrence found that the presence of acute lung injury/acute respiratory distress syndrome and shock at diagnosis was associated with recurrence.³³ All patients who developed VAP recurrence/persistence in our cohort had PaO₂/FiO₂ <200, however, it is unknown if they developed acute respiratory distress syndrome.

Ventilator-associated pneumonia caused by non-fermenting gram-negative bacillus may be a risk factor for VAP persistence.³² This group of pathogens harbors virulence factors that can enable chronic infection in ventilated patients. Our cohort did not have primary VAP with non-fermenting gram-negative bacillus. Therefore, patients with IOF may be at lower risk of having recurrent pneumonia compared with patients who grow targeted, specifically non-fermenting gram-negative, pathogens >100,000 CFU/mL.

In the absence of a specific isolated pathogen, some clinicians may question the necessity of continuing any antibiotic treatment at all. The decision to withhold antibiotic agents completely in IOF may be worthy of separate investigation. Because IOF was recovered from distal airway specimens during a procedure that was initiated in response to clinical signs of pneumonia, our clinicians are less likely to withhold antimicrobial treatment completely, however there is lack of consensus on which antimicrobial agents are indicated. If antimicrobial suppression of the IOF is desired, typical β-lactam agents used for the empiric treatment of VAP (cefepime or piperacillin-tazobactam) provide activity against the majority of these organisms (Streptococcus pneumoniae, β-hemolytic streptococci, viridans strep, Haemophilus spp., and Fusobacterium spp.).

Limitations of our study include its retrospective design and small sample size. Because of the retrospective nature, we could not control for other variables that may have influenced the decision to de-escalate antimicrobial agents. We did not evaluate the impact of concomitant nephrotoxins or vasopressors that could have confounded findings regarding AKI. Although no patient in our cohort grew MRSA in a repeat BAL sample, MRSA nasal swab testing was not performed therefore it is unknown if patients were colonized with MRSA. Although our study utilized a BAL as a surrogate marker for VAP, our patient population had similar baseline characteristics suggestive of worsening respiratory status secondary to an infection, with most patients having PaO₂/FiO₂ ratios <250 and temperatures >100.6°F on the date of BAL. Indeed, in the absence of individual pathogens to guide targeted therapy, the decision to de-escalate antibiotic agents in patients whose BAL cultures grow IOF varies in large part based on attending surgeon preference.

Conclusions

In conclusion, trauma patients who develop VAP with isolated BAL cultures of IOF or mixed flora can safely have anti-MRSA antimicrobial agents discontinued. Potential benefits of discontinuation of anti-MRSA antimicrobial agents include decrease rates of AKI, decrease cost and therapeutic drug monitoring, and decrease in emergence of drug resistance and CDI. Further studies are needed to evaluate whether anti-pseudomonal antimicrobial agents can be safely de-escalated in similar scenarios.

Footnotes

Authors' Contributions

C onceptualization: Scherrer, Harbrecht. Methodology: Scherrer,

Writing–original draft preparation: Scherrer, Kaylor. W riting–review and editing: Caminiti, Harbrecht, McPheeters. D ata curation: Kaylor. Formal analysis: Kaylor. Project administration: McPheeters.

Funding Information

No funding was received for this study.

Author Disclosure Statement

No authors have any conflicts of interest to disclose.

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