Empirical anti-MRSA vs standard antibiotic therapy and risk of 30-day mortality in patients hospitalized for pneumonia.
Open accessAbstract
Importance: Use of empirical broad-spectrum antibiotics for pneumonia has increased owing to concern for resistant organisms, including methicillin-resistant Staphylococcus aureus (MRSA). The association of empirical anti-MRSA therapy with outcomes among patients with pneumonia is unknown, even for high-risk patients. Objective: To compare 30-day mortality among patients hospitalized for pneumonia receiving empirical anti-MRSA therapy vs standard empirical antibiotic regimens. Design, Setting, and Participants: Retrospective multicenter cohort study was conducted of all hospitalizations in which patients received either anti-MRSA or standard therapy for community-onset pneumonia in the Veterans Health Administration health care system from January 1, 2008, to December 31, 2013. Subgroups of patients analyzed were those with initial intensive care unit admission, MRSA risk factors, positive results of a MRSA surveillance test, and positive results of a MRSA admission culture. Primary analysis was an inverse probability of treatment-weighted propensity score analysis using generalized estimating equation regression; secondary analyses included an instrumental variable analysis. Statistical analysis was conducted from June 14 to November 20, 2019. Exposures: Empirical anti-MRSA therapy plus standard pneumonia therapy vs standard therapy alone within the first day of hospitalization. Main Outcomes and Measures: Risk of 30-day all-cause mortality after adjustment for patient comorbidities, vital signs, and laboratory results. Secondary outcomes included the development of kidney injury and secondary infections with Clostridioides difficile, vancomycin-resistant Enterococcus species, or gram-negative bacilli. Results: Among 88 605 hospitalized patients (86 851 men; median age, 70 years [interquartile range, 62-81 years]), empirical anti-MRSA therapy was administered to 33 632 (38%); 8929 patients (10%) died within 30 days. Compared with standard therapy alone, in weighted propensity score analysis, empirical anti-MRSA therapy plus standard therapy was significantly associated with an increased adjusted risk of death (adjusted risk ratio [aRR], 1.4 [95% CI, 1.3-1.5]), kidney injury (aRR, 1.4 [95% CI, 1.3-1.5]), and secondary C difficile infections (aRR, 1.6 [95% CI, 1.3-1.9]), vancomycin-resistant Enterococcus spp infections (aRR, 1.6 [95% CI, 1.0-2.3]), and secondary gram-negative rod infections (aRR, 1.5 [95% CI, 1.2-1.8]). Similar associations between anti-MRSA therapy use and 30-day mortality were found by instrumental variable analysis (aRR, 1.6 [95% CI, 1.4-1.9]) and among patients admitted to the intensive care unit (aRR, 1.3 [95% CI, 1.2-1.5]), those with a high risk for MRSA (aRR, 1.2 [95% CI, 1.1-1.4]), and those with MRSA detected on surveillance testing (aRR, 1.6 [95% CI, 1.3-1.9]). No significant favorable association was found between empirical anti-MRSA therapy and death among patients with MRSA detected on culture (aRR, 1.1 [95% CI, 0.8-1.4]). Conclusions and Relevance: This study suggests that empirical anti-MRSA therapy was not associated with reduced mortality for any group of patients hospitalized for pneumonia. These results contribute to a growing body of evidence that questions the value of empirical use of anti-MRSA therapy using existing risk approaches.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In undifferentiated patients with pneumonia or sepsis, broad-spectrum regimens active against MRSA are associated with higher mortality, especially in patients without MRSA.
“Among undifferentiated patients with pneumonia or sepsis, broad-spectrum regimens including agents active against MRSA were associated with higher mortality, particularly among patients without MRSA [137, 151, 155, 156].”
From Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021 (2021) · cites this paper as [155]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
A Modified Poisson Regression Approach to Prospective Studies with Binary Data
Zou, G. (2004) · American Journal of Epidemiology · doi:10.1093/aje/kwh090 · Cited by 9,767 · see citing works
Mandell, L. A., Wunderink, R. G., Anzueto, A., Bartlett, J. G., Campbell, G. D., Dean, N. C., Dowell, S. F., File, T. M., Musher, D. M., Niederman, M. S., et al. (2007) · Clinical Infectious Diseases · doi:10.1086/511159 · Cited by 6,182 · see citing works
A Prediction Rule to Identify Low-Risk Patients with Community-Acquired Pneumonia
Fine, M. J., Auble, T. E., Yealy, D. M., Hanusa, B. H., Weissfeld, L. A., Singer, D. E., Coley, C. M., Marrie, T. J., & Kapoor, W. N. (1997) · New England Journal of Medicine · doi:10.1056/nejm199701233360402 · Cited by 4,560 · see citing works
Metlay, J. P., Waterer, G. W., Long, A. C., Anzueto, A., Brozek, J., Crothers, K., Cooley, L. A., Dean, N. C., Fine, M. J., Flanders, S. A., et al. (2019) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201908-1581st · Cited by 3,657 · see citing works
A tutorial on propensity score estimation for multiple treatments using generalized boosted models
McCaffrey, D. F., Griffin, B. A., Almirall, D., Slaughter, M. E., Ramchand, R., & Burgette, L. F. (2013) · Statistics in Medicine · doi:10.1002/sim.5753 · Cited by 1,450 · see citing works
Higgins (2002) · doi:10.1002/(issn)1097-0258 · Cited by 1,248 · see citing works
Rubin, D. B. (2007) · Statistics in Medicine · doi:10.1002/sim.2739 · Cited by 1,047 · see citing works
Observational Studies Analyzed Like Randomized Experiments
Hernán, M. Á., Alonso, Á., Logan, R. W., Grodstein, F., Michels, K. B., Willett, W. C., Manson, J. E., & Robins, J. M. (2008) · Epidemiology · doi:10.1097/ede.0b013e3181875e61 · Cited by 822 · see citing works
Early, Goal-Directed Therapy for Septic Shock — A Patient-Level Meta-Analysis
The PRISM Investigators (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1701380 · Cited by 600 · see citing works
Kaplan, V., Angus, D. C., Griffin, M. F., Clermont, G., Watson, R. S., & Linde‐Zwirble, W. T. (2002) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/ajrccm.165.6.2103038 · Cited by 561 · see citing works
Bjørge, T., Tretli, S., & Engeland, A. (2004) · American Journal of Epidemiology · doi:10.1093/aje/ · Cited by 492 · see citing works
Antimicrobial Agents and Chemotherapy
Billard‐Pomares, T., Clermont, O., Castellanos, M., Magdoud, F., Royer, G., Condamine, B., Fouteau, S., Barbe, V., Roche, D., Cruveiller, S., et al. (2013) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac · Cited by 487 · see citing works
Almirall, D., Nahum-Shani, I., Sherwood, N. E., & Murphy, S. A. (2014) · Translational Behavioral Medicine · doi:10.1007/s13142-014-0265-0 · Cited by 453 · see citing works
Jeffres, M. N., Isakow, W., Doherty, J. A., Micek, S. T., & Kollef, M. H. (2007) · Clinical Therapeutics · doi:10.1016/j.clinthera.2007.06.014 · Cited by 333 · see citing works
Messacar, K., Parker, S. K., Todd, J. K., & Dominguez, S. R. (2016) · Journal of Clinical Microbiology · doi:10.1128/jcm.02264-16 · Cited by 329 · see citing works
Lindenauer, P. K., Lagu, T. C., Shieh, M., Pekow, P. S., & Rothberg, M. B. (2012) · JAMA · doi:10.1001/jama.2012.384 · Cited by 295 · see citing works
Risk Factors for Drug-Resistant Pathogens in Community-acquired and Healthcare-associated Pneumonia
Shindo, Y., Ito, R., Kobayashi, D., Ando, M., Ichikawa, M., Shiraki, A., Gotô, Y., Fukui, Y., Iwaki, M., Okumura, J., et al. (2013) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201301-0079oc · Cited by 291 · see citing works
Chakraborty, B., & Murphy, S. A. (2013) · Annual Review of Statistics and Its Application · doi:10.1146/annurev-statistics-022513-115553 · Cited by 288 · see citing works
Toolkit for Weighting and Analysis of Nonequivalent Groups: A tutorial for the twang package
Ridgeway, G. K., McCarey, D., Morral, A. R., Burgette, L. F., & Grin, B. A. (2014) · Cited by 274 · see citing works
Community‐Acquired Pneumonia Requiring Hospitalization
Marrie, T. J., Haldane, E. V., Faulkner, R. S., Durant, H., & Kwan, C. (1985) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.1985.tb01775.x · Cited by 264 · see citing works
Commentary: How to Report Instrumental Variable Analyses (Suggestions Welcome)
Swanson, S. A., & Hernán, M. A. (2013) · Epidemiology · doi:10.1097/ede.0b013e31828d0590 · Cited by 197 · see citing works
Dangerfield, B. S., Chung, A. S., Webb, B. J., & Seville, M. T. (2013) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01805-13 · Cited by 181 · see citing works
Wachter, R. M., Flanders, S. A., Fee, C. R., & Pronovost, P. J. (2008) · Annals of Internal Medicine · doi:10.7326/0003-4819-149-1-200807010-00007 · Cited by 180 · see citing works
Applying Sputum as a Diagnostic Tool in Pneumonia
Ewig, S., Schlochtermeier, M., Goïke, N., & Niederman, M. S. (2002) · CHEST Journal · doi:10.1378/chest.121.5.1486 · Cited by 165 · see citing works
Broad-spectrum antibiotic use and poor outcomes in community-onset pneumonia: A cohort study.
Webb, B. J., Sorensen, J., Jephson, A., Mecham, I., & Dean, N. C. (2019) · European Respiratory Journal · doi:10.1183/13993003.00057-2019 · Cited by 164 · see citing works
Lodise, T. P., Rosenkranz, S. L., Finnemeyer, M., Evans, S. R., Sims, M. D., Zervos, M., Creech, C. B., Patel, P. C., Keefer, M. C., Riska, P. F., et al. (2019) · Clinical Infectious Diseases · doi:10.1093/cid/ciz460 · Cited by 164 · see citing works
Cano, E. L., Haque, N. Z., Welch, V. L. L., Cely, C. M., Peyrani, P., Scerpella, E. G., Ford, K. D., Zervos, M., Ramírez, J. A., & Kett, D. H. (2012) · Clinical Therapeutics · doi:10.1016/j.clinthera.2011.12.013 · Cited by 162 · see citing works
Obituary: pulmonary artery catheter 1970 to 2013
Marik, P. (2013) · Annals of Intensive Care · doi:10.1186/2110-5820-3-38 · Cited by 158 · see citing works
Aliberti, S., Cillóniz, C., Chalmers, J. D., Zanaboni, A. M., Cosentini, R., Tarsia, P., Pesci, A., Blasi, F., & Torres, A. (2013) · Thorax · doi:10.1136/thoraxjnl-2013-203384 · Cited by 140 · see citing works
Community-Acquired Pneumonia Requiring Hospitalization
Jain, S., Self, W. H., & Wunderink, R. G. (2015) · New England Journal of Medicine · doi:10.1056/nejmc1511751 · Cited by 131 · see citing works
Guideline-concordant therapy and outcomes in healthcare-associated pneumonia
Attridge, R. T., Frei, C. R., Restrepo, M. I., Lawson, K. A., Ryan, L., Pugh, M. J., Anzueto, A., & Mortensen, E. M. (2011) · European Respiratory Journal · doi:10.1183/09031936.00141110 · Cited by 112 · see citing works
Two‐Stage Residual Inclusion Estimation in Health Services Research and Health Economics
Terza, J. V. (2017) · Health Services Research · doi:10.1111/1475-6773.12714 · Cited by 100 · see citing works
Falsification Testing of Instrumental Variables Methods for Comparative Effectiveness Research
Pizer, S. D. (2015) · Health Services Research · doi:10.1111/1475-6773.12355 · Cited by 89 · see citing works
Jones, B. E., Jones, M., Huttner, B. D., Stoddard, G. J., Brown, K. A., Stevens, V. W., Greene, T., Sauer, B. C., Madaras‐Kelly, K., Rubin, M. A., et al. (2015) · Clinical Infectious Diseases · doi:10.1093/cid/civ629 · Cited by 84 · see citing works
Self-citationRapid Detection of Methicillin-Resistant Staphylococcus aureus in BAL
Paonessa, J. R., Shah, R. D., Pickens, C. I., Lizza, B. D., Donnelly, H. K., Malczynski, M., Qi, C., & Wunderink, R. G. (2019) · Chest · doi:10.1016/j.chest.2019.02.007 · Cited by 66 · see citing works
Shorr, A. F., Zilberberg, M. D., Micek, S. T., & Kollef, M. H. (2014) · BMC Infectious Diseases · doi:10.1186/s12879-014-0572-6 · Cited by 59 · see citing works
Jones, M., Jernigan, J. A., Evans, M. E., Roselle, G. A., Hatfield, K. M., & Samore, M. H. (2019) · MMWR. Morbidity and Mortality Weekly Report · doi:10.15585/mmwr.mm6809e2 · Cited by 50 · see citing works
Self-citationDetection of respiratory pathogens in clinical samples using metagenomic shotgun sequencing
Qi, C., Hountras, P., Pickens, C. I., Walter, J. M., Kruser, J. M., Singer, B. D., Seed, P. C., Green, S. J., & Wunderink, R. G. (2019) · Journal of Medical Microbiology · doi:10.1099/jmm.0.000968 · Cited by 43 · see citing works
Jones, B. E., South, B. C., Shao, Y., Lu, C. C., Leng, J., Sauer, B. C., Gundlapalli, A., Samore, M., & Zeng, Q. (2018) · Applied Clinical Informatics · doi:10.1055/s-0038-1626725 · Cited by 42 · see citing works
Self-citationMadaras‐Kelly, K., Jones, M., Remington, R. E., Caplinger, C., Huttner, B. D., Jones, B. E., & Samore, M. H. (2015) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkv338 · Cited by 34 · see citing works
Self-citationCommunity-acquired Pneumonia versus Healthcare-associated Pneumonia. The Returning Pendulum
Wunderink, R. G. (2013) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201308-1536ed · Cited by 31 · see citing works
Jones, B. E., Brown, K. A., Jones, M., et al. (2017) · Infection Control and Hospital Epidemiology · doi:10.1017/ice.2017.98 · Cited by 30 · see citing works
Self-citationUnmet diagnostic needs in infectious disease
Blaschke, A. J., Hersh, A. L., Beekmann, S. E., İnce, D., Polgreen, P. M., & Hanson, K. E. (2014) · Diagnostic Microbiology and Infectious Disease · doi:10.1016/j.diagmicrobio.2014.10.005 · Cited by 27 · see citing works
Attridge, R. T., Frei, C. R., Pugh, M. J., Lawson, K. A., Ryan, L., Anzueto, A., Metersky, M. L., Restrepo, M. I., & Mortensen, E. M. (2016) · Journal of Critical Care · doi:10.1016/j.jcrc.2016.08.004 · Cited by 26 · see citing works
Berger, A., Edelsberg, J., Oster, G., Huang, X., & Weber, D. J. (2013) · The American Journal of the Medical Sciences · doi:10.1097/maj.0b013e318294833f · Cited by 23 · see citing works
Webb, B. J., Jones, B. E., & Dean, N. C. (2016) · Current Opinion in Infectious Diseases · doi:10.1097/qco.0000000000000254 · Cited by 23 · see citing works
Self-citationToolkit for Weighting and Analysis of Nonequivalent Groups: A Tutorial for the R TWANG Package
Ridgeway, G., McCaffrey, D. F., Morral, A. R., et al. (2014) · RAND Corporation eBooks · doi:10.7249/tl136.1 · Cited by 21 · see citing works
Jones, B. E., Haroldsen, C. L., Madaras‐Kelly, K., Goetz, M. B., Ying, J., Sauer, B. C., Jones, M., Leecaster, M. K., Greene, T., Fridkin, S. K., et al. (2018) · Medical Care · doi:10.1097/mlr.0000000000000916 · Cited by 15 · see citing works
Self-citationWithdrawal of ‘Xigris’ from the market: old and new lessons
Poole, D., Bertolini, G., & Garattini, S. K. (2012) · Journal of Epidemiology & Community Health · doi:10.1136/jech-2012-200977 · Cited by 14 · see citing works
Jones, M., Huttner, B. D., Leecaster, M. K., Huttner, A. C., Damal, K., Tanner, W. R., Nielson, C., Rubin, M. A., Goetz, M. B., Madaras‐Kelly, K., et al. (2014) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dku299 · Cited by 11 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021.
Evans, L., Rhodes, A., Alhazzani, W., Antonelli, M., Coopersmith, C. M., French, C., Machado, F. R., Mcintyre, L., Ostermann, M., Prescott, H. C., et al. (2021) · Critical Care Medicine · doi:10.1097/ccm.0000000000005337 · Cited by 2,935 · see citing works
Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021
Evans, L., Rhodes, A., Alhazzani, W., Antonelli, M., Coopersmith, C. M., French, C., Machado, F. R., Mcintyre, L., Ostermann, M., Prescott, H. C., et al. (2021) · Intensive Care Medicine · doi:10.1007/s00134-021-06506-y · Cited by 5,082 · see citing works
Antibiotic De-escalation in adults hospitalized for community-onset Sepsis
Gupta, A. B., Heath, M., Walzl, E., Ratz, D., Munroe, E., Vaughn, V. M., Horowitz, J. K., Czilok, T., Petty, L. A., Gandhi, T. N., et al. (2026) · JAMA Internal Medicine · doi:10.1001/jamainternmed.2025.6919 · Cited by 14 · see citing works
- Authors
- Jones, B. E., Ying, J., Stevens, V., Haroldsen, C., He, T., Nevers, M., Christensen, M. A., Nelson, R. E., Stoddard, G. J., Sauer, B. C., Yarbrough, P. M., Jones, M. M., Goetz, M. B., Greene, T., & Samore, M. H.
- Affiliations
- University of Utah (US)
- VA Greater Los Angeles Healthcare System (US)
- Corresponding author
- Jones, Barbara Ellen
- ORCID
- Venue
- JAMA Internal Medicine
- Publisher
- American Medical Association (AMA)
- Published
- 2020-04-01
- Volume
- 180
- Issue
- 4
- Pages
- 552
- ISSN
- 2168-6106 (ISSN-L)
- PMC
- PMC7042818
- OpenAlex
- W3005615873
- Semantic Scholar
- aa779423e5b2b385fddf89f580722b862ee01a13
- Cited by
- 122
- References
- 50
- Citations by year
- 2026: 12 · 2025: 33 · 2024: 20 · 2023: 19 · 2022: 19 · 2021: 11 · 2020: 8
- FWCI
- 10.21
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- JAMA Internal Medicine (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by-nc-nd)
- Funders
- U.S. Department of Veterans Affairs (I50 HX001240, IK2 HX001908)
- National Institutes of Health (UL1TR002538)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Epidemiology › Pneumonia and Respiratory Infections
- Life Sciences › Immunology and Microbiology › Applied Microbiology and Biotechnology › Antibiotic Use and Resistance
- Health Sciences › Medicine › Infectious Diseases › Antimicrobial Resistance in Staphylococcus
- Keywords
- methicillin-resistant Staphylococcus aureus, community-onset pneumonia, 30-day mortality, broad-spectrum antibiotics, kidney injury, Clostridium difficile infection, vancomycin-resistant enterococci, Gram-negative bacilli, secondary infection, veterans, intensive care unit admission, antibiotic stewardship, antimicrobial resistance
- MeSH terms
- Aged, Aged, 80 and over, Anti-Bacterial Agents, Female, Humans, Male, Middle Aged, Pneumonia, Staphylococcal, Retrospective Studies, Hospital Mortality, Pneumonia, Bacterial, Methicillin-Resistant Staphylococcus aureus
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
