Abstract
Introduction
When methicillin-resistant Staphylococcus aureus (MRSA) is the causative pathogen in pneumonia, in-hospital mortality rate is approximately 31.2%. However, the occurrence of MRSA pneumonia is uncommon, with a reported incidence of approximately 4.2%. Vancomycin is often empirically used for MRSA pneumonia coverage, but can lead to serious harm. The purpose of this study was to measure the impact of a pharmacy-driven MRSA nares testing protocol on vancomycin and linezolid prescribing patterns and clinical outcomes in patients diagnosed with pneumonia after removal of immediate educational intervention.
Methods
This single-centre, quasi-experimental study evaluated the use of a MRSA nasal swab on patients diagnosed with community-acquired pneumonia, hospital-acquired pneumonia and ventilator-associated pneumonia. This study consisted of three phases, the preimplementation phase, the active/educational phase and the postimplementation phase. The primary outcome was intravenous anti-MRSA antibiotic duration of therapy. Secondary outcomes included the occurrence of acute kidney injury, duration of hospital stay, number of vancomycin levels obtained, the number of MRSA nares swabs ordered and time points in the MRSA nares collection process.
Results
The preimplementation phase (n=39), the active phase (n=45) and the postimplementation phase (n=26) demonstrated similar baseline characteristics. The primary outcome for duration of anti-MRSA therapy 0–72 hours was 61.5% vs 77.8% vs 76.9% (p=0.19). Acute kidney injury was decreased throughout the study at 25.6%, 24.4% and 16.7% (p=0.32). The number of MRSA nares swabs ordered were 23.1%, 60% and 30.8% in each of the phases, respectively (p=0.49).
Discussion
Our novel approach to measuring the impact of pharmacist education and ordering of MRSA nasal swabs has demonstrated benefits that were sustained for a short period after the intervention was removed. Additional study is required to determine the long-term impact.
Conclusion
The implementation of a hospital-wide anti-MRSA protocol in patients with confirmed or suspected pneumonia indicated sustained changes for at least 3 months after direct intervention.
Keywords: Health policy; EDUCATION, PHARMACY; PHARMACY ADMINISTRATION; MICROBIOLOGY; PHARMACY SERVICE, HOSPITAL
WHAT IS ALREADY KNOWN ON THIS TOPIC
Current literature has indicated a significant decrease in overall mean duration of anti-methicillin-resistant Staphylococcus aureus (MRSA) antibiotic therapy with the use of MRSA nares testing protocols.
However, no studies have demonstrated the benefit of such protocols to the organisation and its patients after the removal of an active educational and interventional phase.
WHAT THIS STUDY ADDS
This is significant because it introduces a novel approach to the implementation of new hospital policies that help direct the organisation’s leadership on when to alter their focus once a new policy is initiated.
HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY
This study introduces the feasibility for sustained results of new initiatives to remain in effect for up to 3 months without the need for re-education, allowing for the focus on new initiatives.
Introduction
Methicillin-resistant Staphylococcus aureus (MRSA) is a serious cause of community-acquired pneumonia (CAP), hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP). In patients being treated for MRSA pneumonia, the risk of in-hospital mortality is 31.2%.1 The incidence of MRSA pneumonia is different, depending on the classification of pneumonia. For CAP, the prevalence of S. aureus is 1.8%, whereas in HAP or VAP, S. aureus is isolated in 15%–18% of the cases.2 3 The prevalence of S. aureus being methicillin-resistant ranges from 37% to 54.4%. With the use of anti-MRSA antibiotics such as vancomycin, the patient is placed at an increased associated risk of acute kidney injury, with a relative risk of 2.45 compared with patients receiving a non-glycopeptide antibiotic.4 Therefore, the use of empirical anti-MRSA antibiotic coverage in patients with pneumonia is important, but can be harmful when unnecessary.
Depending on the patient’s risk factors, an antibiotic treatment plan could consist of an anti-MRSA antibiotic, since it can be especially difficult to determine a definitive pathogen since microbiological testing may require invasive testing and a few days’ waiting period for results. Furthermore, the resulting cultures may be affected by contamination or chronic microbial colonisation.
There have been several published studies that support the de-escalation of vancomycin therapy by a negative MRSA nares swab.5–7 In a meta-analysis of 22 studies with 5163 patients, there was clinical utility in using MRSA nasal screening for predicting MRSA pneumonia, which resulted in a 96.5% negative predictive value.8 Although many of these studies agree that a positive MRSA is not diagnostic of MRSA pneumonia, they suggest that a negative MRSA nares swab is an appropriate screening tool for early de-escalation of antibiotic therapy for pneumonia.
A 2017 single-centre, retrospective study found a significant decrease in mean duration of empirical vancomycin therapy, from 4.2 days of therapy to 2.1 days of therapy, with a MRSA nares de-escalation protocol compared with groups without an MRSA nares protocol in place.9 One study found significantly lower intensive care unit length of stay when anti-MRSA therapy was de-escalated with MRSA nares swab in patients with pneumonia.10
Patient safety with early de-escalation of antibiotic therapy has also been studied more comprehensively in patients with pneumonia. It was found that there were no significant differences in the rate of acute kidney injury, 30-day readmission or 30-day mortality between patients that had their anti-MRSA medication therapy withdrawn after the MRSA nares results compared with those in the preimplementation group.11 These results demonstrate the clinical safety and value of using MRSA nares swab to optimise anti-MRSA therapy in pneumonia.
After the clinical benefits in patient care were demonstrated, there has been increased momentum to implement hospital-wide MRSA nares protocols in patients being treated with anti-MRSA therapy for confirmed or suspected pneumonia. However, quantification of the impact of a new anti-MRSA protocol after the removal of the direct intervention has not been studied.
This three-phase study aimed to examine the effect of a novel hospital-wide MRSA nares de-escalation protocol through retrospective, active phase and postimplementation measurements to assess the impact of a brief intervention on patient outcomes and provider practice.
Methods
This was a single-centre, quasi-experimental study performed at a 600-bed community teaching hospital, located in north-eastern USA, in patients with suspected or confirmed pneumonia.
This study consisted of three phases, the preimplementation phase, the active phase and the postimplementation phase. The timing for each was 15 August 2021 through 15 November 2021, 16 November 2021 through 15 February 2022 and 16 February 2022 through 15 May 2022, respectively.
The preimplementation phase was a retrospective design intended to measure the current hospital practice of treating patients with suspected/confirmed MRSA pneumonia. During the preimplementation phase, only the patient’s provider was able to order a MRSA nares swab and there was no direct involvement of the pharmacy in the patient’s treatment regimen.
During the active phase, a Pharmacy & Therapeutics (P&T) policy was created by the pharmacy team to outline the roles and responsibilities of the pharmacist for MRSA nares swab ordering and resulting actions and subsequently approved by the interdisciplinary hospital-wide P&T committee . After P&T approval, provider teams (eg, hospitalists, geriatricians, infectious diseases) were educated on the new initiative, and the pharmacy staff were permitted to order the swab in patients. After the 4–6 hours waiting time for the MRSA nares PCR swab, a pharmacist could contact the provider team for a discussion on discontinuing intravenous anti-MRSA therapy if the result was negative.
For the postimplementation phase, direct provider team educational intervention was withheld. No pharmacist-generated orders for MRSA nares swabs were entered. No interventions to recommend discontinuation of intravenous anti-MRSA therapy were provided from the pharmacists. Prescribers were free to order the MRSA nares at their discretion. Notably, there was little turnover in staff over the course of the study and therefore it was primarily the same provider practices evaluated in each phase.
Patients were included if they were 18 years old or older, had suspected or confirmed CAP, HAP or VAP, were administered at least one dose of the anti-MRSA intravenous agent, vancomycin or linezolid. Patients were excluded if they had a MRSA infection within the previous 30 days, diagnosed with cystic fibrosis, were being treated for a concomitant infection, pregnant or breastfeeding, currently incarcerated, or were treated in the intensive care unit of the hospital during the hospital stay as routine practice for patients in the intensive care unit already includes MRSA nares testing for infection control purposes.
To accurately identify our patient population, a report from the electronic health record was generated for all patients within the hospital that were prescribed intravenous vancomycin or linezolid for the specific indication of CAP, HAP or VAP. The inclusion and exclusion criteria were applied based on a manual patient chart review.
The primary outcome of this study was duration of anti-MRSA therapy, measured categorically, as either receiving 0–72 hours of therapy or 72+ hours of therapy. The outcome was dichotomised to assess early anti-MRSA antibiotic de-escalation while eliminating the impact of any imbalances in antibiotic indications requiring long-term anti-MRSA therapy.
The secondary outcomes were the occurrence of acute kidney injury, length of hospital stay, vancomycin dosing personnel (pharmacist or provider), number of MRSA nares swabs performed, time to swab from the initiation of intravenous vancomycin or linezolid therapy, and the time from nares swab performed to the discontinuation of vancomycin or linezolid.
Acute kidney injury was defined as an increase in serum creatinine of ≥0.3 mg/dL after the initiation of the anti-MRSA antibiotic and measured up to 48 hours after the discontinuation of the antibiotic.12
Baseline data included age, gender, weight, procalcitonin, type of pneumonia, presence of COVID-19, anti-MRSA therapy used, dosing personnel (pharmacist or provider team), the obtainment of urine cultures, blood cultures, sputum cultures and respiratory pathogen panels.
The data were collected and analysed through Microsoft Excel, V.16.16.13. The primary outcome was analysed using logistic regression comparing all three phases. The secondary outcomes were analysed using a χ2 test or Student’s t-test to compare the preimplementation phase to the postimplementation phase. A value of p<0.05 was considered statistically significant.
Results
A total of 351 patients were screened. The most common patient exclusions were for admittance into an intensive care unit (33%) or treatment for a concomitant infection (32.8%). The included patient population consisted of 110 patients, with 39 patients in the preimplementation phase, 45 patients in the active phase and 26 patients in the postimplementation phase (table 1).
Table 1.
Patient baseline characteristics
| Preimplementation phase (n=39) | Active phase (n=45) | Postimplementation phase (n=26) | |
| Age, years, mean (SD) | 74.1 (13.7) | 68.8 (18.9) | 70.1 (19.1) |
| Female, N (%) | 20 (51.3) | 20 (44.4) | 18 (69.2) |
| Weight, kg, mean (SD) | 73.6 (21.02) | 71.3 (16.88) | 83.1 (17.73) |
| Procalcitonin, μmol, median (range) | 0.18 (0.05–24.3) | 0.35 (0.03–224.76) | 0.32 (0.13–2.86) |
| Pneumonia, N (%) | |||
| CAP | 27 (69.2) | 30 (66.6) | 17 (65.4) |
| HAP | 12 (30.8) | 15 (33.4) | 9 (34.6) |
| VAP | 0 (0) | 0 (0) | 0 (0) |
| COVID-19, N (%) | 1 (2.6) | 8 (17.8) | 3 (11.5) |
| Anti-MRSA therapy, N (%) | |||
| Vancomycin | 39 (100) | 42 (93.3) | 26 (100) |
| Area under the curve (AUC)-based dosing by pharmacy, N (%) | 2 (5.1) | 5 (11.9) | 4 (15.4) |
| Sputum culture (% of patients) | 23.1 | 24 | 15.4 |
| Respiratory pathogen panel | 33.3 | 33.3 | 34.6 |
| Blood cultures | 87.2 | 75 | 76.9 |
| Urine cultures | 82.1 | 73.3 | 46.1 |
CAP, community-acquired pneumonia; HAP, hospital-acquired pneumonia; MRSA, methicillin-resistant Staphylococcus aureus; VAP, ventilator-associated pneumonia.
Baseline characteristics included a majority of female patients, with a mean age for each group ranging from 68 years to 74 years. There were consistently more patients diagnosed with CAP (69.2%, 66.6% and 65.4%) than the other classifications of pneumonia when comparing the retrospective phase, active phase and postimplementation phase. Patients diagnosed with COVID-19 were 2.6%, 17.8% and 11.5%. Anti-MRSA medication dosing by pharmacy was 5.1%, 11.9% and 15.4% (p=0.16). For microbiology testing, sputum cultures were obtained on 23.1%, 24% and 15.4% of patients, a respiratory pathogen panel was performed on 33.3%, 33.3% and 34.6%, and blood cultures were performed on 87.2%, 75% and 76.9%. Urine cultures were obtained in 82.1%, 73.3% and 46.1% of patients (table 1).
During the active phase, the pharmacist reached out to the patient’s providing team 10 times and received 5 responses. Those responses varied from agreeing to discontinue the antibiotic to discussing the negative MRSA nares result on morning rounds with the attending physician. From the 27 included patients that received a MRSA nares swab, 4 patients (14.8%) were colonised with methacillin-susceptible Staphylococcus aurues and 23 patients resulted negative (table 2).
Table 2.
Active phase
| Active phase | |
| MRSA nares swabs | |
| Ordered | 27 |
| MSSA (%) | 4 (14.8) |
| Negative (%) | 23 (85.2) |
| Reached out to team | 10 |
| Response provided by team | 5 |
MRSA, methicillin-resistant Staphylococcus aureus.
The primary outcome (table 3), patient duration of intravenous anti-MRSA therapy from 0 hours to 72 hours, was 61.5%, 77.8% and 76.9%, in the preimplementation phase, active phase and postimplementation phase, respectively (p=0.19). Comparing the mean duration of therapy between the preimplementation and postimplementation phases was found to be marginally significant (p=0.053).
Table 3.
Primary outcome
| Preimplementation phase (n=39) |
Active phase (n=45) |
Postimplementation (n=26) |
P value | |
| Patient duration of intravenous anti-MRSA therapy (0–72 hours) | 61.5% | 77.8% | 76.9% | 0.19 |
MRSA, methicillin-resistant Staphylococcus aureus.
For secondary endpoints (table 4), the occurrence of acute kidney injury was 25.6%, 24.4% and 16.7% (p=0.32). The percentage of patients with 0–1 vancomycin levels obtained was 74.4%, 72.1% and 84.6%. The length of hospital stay was 8.8 days, 7.9 days and 7.6 days. The number of MRSA nares swabs ordered between the three groups was 23.1%, 60% and 30.8% (p<0.001). The median time from initiation of the anti-MRSA antibiotic to the time the MRSA nares swab was performed was 15.1 hours, 20.2 hours and 9.1 hours (p=0.13). The time from MRSA nares swab to anti-MRSA antibiotic discontinuation was 80.3 hours, 31.6 hours and 23.5 hours (p=0.27).
Table 4.
Secondary outcomes
| Preimplementation phase (n=39) | Active phase (n=45) | Postimplementation (n=26) | P value | |
| Acute kidney injury | 10 (25.6) | 11 (24.4) | 4 (16.7) | 0.32 |
| Number of vancomycin levels, N (%) | ||||
| 0–1 | 29 (74.4) | 31 (72.1) | 22 (84.6) | 0.32 |
| 2+ | 10 (25.6) | 12 (28.6) | 4 (15.4) | |
| Length of hospital stay, days, median (SD) | 8.8 (8.7) | 7.9 (8.3) | 7.5 (16.9) | 0.54 |
| MRSA nares swabs ordered | 9 (23.1) | 27 (60) | 8 (30.8) | <0.001 |
| Time to swab, hours, median (range) | 15.1 (0.9–104.7) | 20.2 (0.32–137.3) | 9.1 (1.2–26.6) | 0.13 |
| Swab taken to discontinuation, hours, median (range) | 80.3 (14.8–178.7) | 31.6 (3.5–227.4) | 23.5 (13.2–33.7) | 0.27 |
MRSA, methicillin-resistant Staphylococcus aureus.
Discussion
The use of a MRSA nares swab is increasingly used for patients treated with anti-MRSA therapy for confirmed or suspected pneumonia. However, quantifying the impact of a new anti-MRSA protocol in these patients after the removal of intervention and education has not been studied, as many protocols continue with direct intervention of pharmacy personnel.
Aligning with previous literature studying the impact of a MRSA nares protocol implementation, our intervention demonstrated beneficial effects. While many studies have found decreases in antibiotic use with similar interventions, our study is unique in that we found antibiotic use reductions that persisted beyond the duration of the intervention .7 9 13 14
This primary endpoint was not associated with any adverse clinical secondary outcomes. The occurrence of acute kidney injury between preimplementation and postimplementation of a MRSA nares protocol in pneumonia has shown that the frequency of acute kidney injury is not statistically significant.4 8 Our study findings are similar in which there was no significant difference in the percentages of acute kidney injury; however there was an observed trending decrease between the groups. This finding could potentially be explained by the increased percentage of patients having their intravenous anti-MRSA agents dosed by pharmacy. In addition, length of hospital stay in our study was not significant between groups, which is supported by a retrospective study performed in patients with CAP, HAP or VAP.14 These findings could potentially be explained by the trend of decreased length of anti-MRSA antibiotic therapy. The active phase time to MRSA nares swab was longer than each of the other phases. While the reason for this is unclear, it may be accounted for by increases in our increased hospital patient census and decreases in labour resources during a coronavirus and winter surge.
In a study by Baby et al, there was significant reduction in the number of vancomycin levels obtained when comparing the preimplementation and postimplementation periods.13 While our study did not find a significant difference in the number of vancomycin levels obtained, there was a similar trend as the postimplementation part of our study had the largest percentage of patients with only 0–1 vancomycin levels.
There were multiple limitations to this study. This study was a single-centre study with results that may interfere with external validity. The study was potentially underpowered to identify important differences in outcomes between groups since operational limitations in pharmacy resources led a 3-month study timeframe and 10 provider contacts based on negative MRSA nares results. Local prevalence is an important factor in considering the negative predictive value of the MRSA nares PCR result and therefore the appropriateness of anti-MRSA de-escalation. Sites considering implementing this process should consider their local prevalence of MRSA in order to determine how negative MRSA nares PCR results should be used to inform antibiotic therapy.
Another limitation of this study was the lack of confounder mitigation measures when quantifying acute kidney injury (AKI). Many factors that contribute to AKI, such as concomitant use of nephrotoxic medications, age and administration of iodine-based contrast media, were not accounted for. Ultimately, the study was underpowered to assess the impact on AKI. Lastly, based on the trial design, patients who had MRSA swabs tested prior to any anti-MRSA therapy were not included in the study. Therefore, the impact of this intervention may be underestimated.
Further research will be needed in order to determine the impact of a MRSA nares protocol with a longer follow-up period in order to best evaluate its lasting effects.
Conclusion
In this single-centre, quasi-experimental study performed in patients with suspected or confirmed pneumonia, the results indicated at least a 3-month sustained impact of an anti-MRSA protocol for patients. This was demonstrated by a decrease in the duration of intravenous anti-MRSA therapy, a lower occurrence of acute kidney injury, and through optimising the process of MRSA nares collection and discontinuation of antibiotic therapy.
Acknowledgments
The authors thank Dr Alison Brophy and Antai Wang for their assistance on this project.
Footnotes
Contributors: KD and SS made significant contributions to the design and implementation of this study, interpretation of the data, assisted in the development and revisions of the manuscript and, agreed on the final version to be published. KD is guarantor.
Funding: The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests: None declared.
Provenance and peer review: Not commissioned; externally peer reviewed.
Data availability statement
Data are available upon reasonable request.
Ethics statements
Patient consent for publication
Not applicable.
Ethics approval
Institutional review board (IRB) approval was obtained.
References
- 1. Sakamoto Y, Yamauchi Y, Jo T, et al. In-hospital mortality associated with community-acquired pneumonia due to methicillin-resistant staphylococcus aureus: a matched-pair cohort study. BMC Pulm Med 2021;21:345. 10.1186/s12890-021-01713-1 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2. Cukic V, Hadzic A. The most common detected bacteria in sputum of patients with community acquired pneumonia (CAP) treated in hospital. Med Arch 2016;70:354–8. 10.5455/medarh.2016.70.354-358 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3. Mazloomirad F, Hasanzadeh S, Sharifi A, et al. Identification and detection of pathogenic bacteria from patients with hospital-acquired pneumonia in southwestern Iran; evaluation of biofilm production and molecular typing of bacterial isolates. BMC Pulm Med 2021;21:408. 10.1186/s12890-021-01773-3 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4. Sinha Ray A, Haikal A, Hammoud KA, et al. Vancomycin and the risk of AKI: a systematic review and meta-analysis. Clin J Am Soc Nephrol 2016;11:2132–40. 10.2215/CJN.05920616 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5. Smith MN, Erdman MJ, Ferreira JA, et al. Clinical utility of methicillin-resistant staphylococcus aureus nasal polymerase chain reaction assay in critically ill patients with nosocomial pneumonia. J Crit Care 2017;38:168–71. 10.1016/j.jcrc.2016.11.008 [DOI] [PubMed] [Google Scholar]
- 6. Giancola SE, Nguyen AT, Le B, et al. Clinical utility of a nasal swab methicillin-resistant staphylococcus aureus polymerase chain reaction test in intensive and intermediate care unit patients with pneumonia. Diagn Microbiol Infect Dis 2016;86:307–10. 10.1016/j.diagmicrobio.2016.08.011 [DOI] [PubMed] [Google Scholar]
- 7. Woolever NL, Schomberg RJ, Cai S, et al. Pharmacist-driven MRSA nasal PCR screening and the duration of empirical vancomycin therapy for suspected MRSA respiratory tract infections. Mayo Clin Proc Innov Qual Outcomes 2020;4:550–6. 10.1016/j.mayocpiqo.2020.05.002 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8. Parente DM, Cunha CB, Mylonakis E, et al. The clinical utility of methicillin-resistant Staphylococcus aureus (MRSA) nasal screening to rule out MRSA pneumonia: a diagnostic meta-analysis with antimicrobial stewardship implications. Clin Infect Dis 2018;67:1–7. 10.1093/cid/ciy024 [DOI] [PubMed] [Google Scholar]
- 9. Willis C, Allen B, Tucker C, et al. Impact of a pharmacist-driven methicillin-resistant staphylococcus aureus surveillance protocol. Am J Health Syst Pharm 2017;74:1765–73. 10.2146/ajhp160964 [DOI] [PubMed] [Google Scholar]
- 10. Siddiqui AH, Koirala J. Methicillin resistant staphylococcus aureus. In: StatPearls. Treasure Island (FL): StatPearls Publishing, 2022. Available: https://www.ncbi.nlm.nih.gov/books/NBK482221/ [PubMed] [Google Scholar]
- 11. Pham SN, Sturm AC, Jacoby JS, et al. Impact of a pharmacist-driven MRSA nasal PCR protocol on pneumonia therapy. Hosp Pharm 2021;56:221–7. 10.1177/0018578719888906 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12. Kidney disease: improving global outcomes (KDIGO). acute kidney injury work group. KDIGO clinical practice guidelines for acute kidney injury. Kidney Int Suppl 2012;2:1. 10.1038/kisup.2012.1 [DOI] [Google Scholar]
- 13. Baby N, Faust AC, Smith T, et al. Nasal methicillin-resistant Staphylococcus aureus (MRSA) PCR testing reduces the duration of MRSA-targeted therapy in patients with suspected MRSA pneumonia. Antimicrob Agents Chemother 2017;61:e02432-16. 10.1128/AAC.02432-16 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14. Dunaway S, Orwig KW, Arbogast ZQ, et al. Evaluation of a pharmacy-driven methicillin-resistant Staphylococcus aureus surveillance protocol in pneumonia. Int J Clin Pharm 2018;40:526–32. 10.1007/s11096-018-0647-3 [DOI] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
Data are available upon reasonable request.