Third generation cephalosporins and piperacillin/tazobactam have distinct impacts on the microbiota of critically ill patients
Open accessAbstract
Effective implementation of antibiotic stewardship, especially in critical care, is limited by a lack of direct comparative investigations on how different antibiotics impact the microbiota and antibiotic resistance rates. We investigated the impact of two commonly used antibiotics, third-generation cephalosporins (3GC) and piperacillin/tazobactam (TZP) on the endotracheal, perineal and faecal microbiota of intensive care patients in Australia. Patients exposed to either 3GC, TZP, or no β-lactams (control group) were sampled over time and 16S rRNA amplicon sequencing was performed to examine microbiota diversity and composition. While neither treatment significantly affected diversity, numerous changes to microbiota composition were associated with each treatment. The shifts in microbiota composition associated with 3GC exposure differed from those observed with TZP, consistent with previous reports in animal models. This included a significant increase in Enterobacteriaceae and Enterococcaceae abundance in endotracheal and perineal microbiota for those administered 3GC compared to the control group. Culture-based analyses did not identify any significant changes in the prevalence of specific pathogenic or antibiotic-resistant bacteria. Exposure to clinical antibiotics has previously been linked to reduced microbiota diversity and increased antimicrobial resistance, but our results indicate that these effects may not be immediately apparent after short-term real-world exposures.
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?
Center-specific differences in broad-spectrum antibiotic use, with cefepime only administered in US patients, could confound microbiome signatures given its narrower antimicrobial spectrum.
“Of note in our study, we observed center-specific differences in the use of broad-spectrum antibiotics. Specifically, cefepime was only administered in US patients, which could confound microbiome signatures given its narrower anti-microbial activity spectrum as compared to other high-risk antibiotics43.”
From A non-antibiotic-disrupted gut microbiome is associated with clinical responses to CD19-CAR-T cell cancer immunotherapy (2023) · cites this paper as [43]
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
QIIME allows analysis of high-throughput community sequencing data
Caporaso, J. G., Kuczynski, J., Stombaugh, J., Bittinger, K., Bushman, F. D., Costello, E. K., Fierer, N., Peña, A. G., Goodrich, J. K., Gordon, J. I., et al. (2010) · Nature Methods · doi:10.1038/nmeth.f.303 · Cited by 34,887 · see citing works
Metagenomic biomarker discovery and explanation
Segata, N., Izard, J., Waldron, L., Gevers, D., Miropolsky, L., Garrett, W. S., & Huttenhower, C. (2011) · Genome Biology · doi:10.1186/gb-2011-12-6-r60 · Cited by 16,192 · see citing works
Greengenes, a Chimera-Checked 16S rRNA Gene Database and Workbench Compatible with ARB
DeSantis, T. Z., Hugenholtz, P., Larsen, N., Rojas, M., Brodie, E. L., Keller, K., Huber, T., Dalevi, D., Hu, P., & Andersen, G. L. (2006) · Applied and Environmental Microbiology · doi:10.1128/aem.03006-05 · Cited by 10,891 · see citing works
Global patterns of 16S rRNA diversity at a depth of millions of sequences per sample
Caporaso, J. G., Lauber, C. L., Walters, W. A., Berg-Lyons, D., Lozupone, C., Turnbaugh, P. J., Fierer, N., & Knight, R. D. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1000080107 · Cited by 9,633 · see citing works
Ultra-high-throughput microbial community analysis on the Illumina HiSeq and MiSeq platforms
Caporaso, J. G., Lauber, C. L., Walters, W. A., Berg-Lyons, D., Huntley, J., Fierer, N., Owens, S. M., Betley, J., Fraser, L., Bauer, M., et al. (2012) · The ISME Journal · doi:10.1038/ismej.2012.8 · Cited by 8,839 · see citing works
Kumar, A., Roberts, D., Wood, K. E., Light, B., Parrillo, J. E., Sharma, S., Suppes, R., Feinstein, D., Zanotti, S., Taiberg, L., et al. (2006) · Critical Care Medicine · doi:10.1097/01.ccm.0000217961.75225.e9 · Cited by 6,109 · see citing works
Rinninella, E., Raoul, P., Cintoni, M., Franceschi, F., Miggiano, G. A. D., Gasbarrini, A., & Mele, M. C. (2019) · Microorganisms · doi:10.3390/microorganisms7010014 · Cited by 3,462 · see citing works
Dethlefsen, L., & Relman, D. A. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1000087107 · Cited by 2,421 · see citing works
Effect of antimicrobial agents on the ecological balance of human microflora
Sullivan, Å., Edlund, C., & Nord, C. E. (2001) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(01)00066-4 · Cited by 816 · see citing works
Metabolic Effects of Intermittent Fasting
Patterson, R. E., & Sears, D. D. (2017) · Annual Review of Nutrition · doi:10.1146/annurev-nutr-071816-064634 · Cited by 810 · see citing works
The intestinal microbiota: Antibiotics, colonization resistance, and enteric pathogens
Kim, S., Covington, A., & Pamer, E. G. (2017) · Immunological Reviews · doi:10.1111/imr.12563 · Cited by 741 · see citing works
Antibiotics as deep modulators of gut microbiota: between good and evil
Ianiro, G., Tilg, H., & Gasbarrini, A. (2016) · Gut · doi:10.1136/gutjnl-2016-312297 · Cited by 629 · see citing works
Reproducible Community Dynamics of the Gastrointestinal Microbiota following Antibiotic Perturbation
Antonopoulos, D. A., Huse, S. M., Morrison, H. G., Schmidt, T. M., Sogin, M. L., & Young, V. B. (2009) · Infection and Immunity · doi:10.1128/iai.01520-08 · Cited by 545 · see citing works
Assembly of the human intestinal microbiota
Dethlefsen, L., Eckburg, P. B., Bik, E. M., & Relman, D. A. (2006) · Trends in Ecology & Evolution · doi:10.1016/j.tree.2006.06.013 · Cited by 509 · see citing works
Strategies to Minimize Antibiotic Resistance
Lee, C.-R., Cho, I., Jeong, B. C., & Lee, S. H. (2013) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph10094274 · Cited by 456 · see citing works
Extreme Dysbiosis of the Microbiome in Critical Illness
McDonald, D., Ackermann, G., Khailova, L., Baird, C., Heyland, D., Kozar, R., Lemieux, M., Derenski, K., King, J., Vis-Kampen, C., et al. (2016) · mSphere · doi:10.1128/msphere.00199-16 · Cited by 426 · see citing works
Karanika, S., Paudel, S. R., Grigoras, C. A., Kalbasi, A., & Mylonakis, E. E. (2016) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00825-16 · Cited by 411 · see citing works
Antimicrobial Therapy in Critically Ill Patients
Pea, F., Viale, P., & Furlanut, M. (2005) · Clinical Pharmacokinetics · doi:10.2165/00003088-200544100-00002 · Cited by 329 · see citing works
Antibiotic use and microbiome function
Ferrer, M., Méndez–García, C., Rojo, D., Barbas, C., & Moyá, A. (2016) · Biochemical Pharmacology · doi:10.1016/j.bcp.2016.09.007 · Cited by 300 · see citing works
Price, R., MacLennan, G., & Glen, J. B. (2014) · BMJ · doi:10.1136/bmj.g2197 · Cited by 297 · see citing works
Probiotic and synbiotic therapy in critical illness: a systematic review and meta-analysis
Manzanares, W., Lemieux, M., Langlois, P. L., & Wischmeyer, P. E. (2016) · Critical Care · doi:10.1186/s13054-016-1434-y · Cited by 295 · see citing works
Lankelma, J. M., van Vught, L. A., Belzer, C., Schultz, M. J., van der Poll, T., de Vos, W. M., & Wiersinga, W. J. (2016) · Intensive Care Medicine · doi:10.1007/s00134-016-4613-z · Cited by 279 · see citing works
Ng, K. M., Aranda-Díaz, A., Tropini, C., Frankel, M. R., Treuren, W. V., O’Loughlin, C. T., Merrill, B. D., Yu, F. B., Pruss, K. M., Oliveira, R. A., et al. (2019) · Cell Host & Microbe · doi:10.1016/j.chom.2019.10.011 · Cited by 270 · see citing works
Sharma, N., Bhatia, S., Sodhi, A. S., & Batra, N. (2018) · AIMS Microbiology · doi:10.3934/microbiol.2018.1.42 · Cited by 263 · see citing works
Impact of antimicrobial therapy on the gut microbiome
Bhalodi, A. A., van Engelen, T. S. R., Virk, H. S., & Wiersinga, W. J. (2018) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dky530 · Cited by 198 · see citing works
Antimicrobial Resistance in the Intensive Care Unit
MacVane, S. H. (2016) · Journal of Intensive Care Medicine · doi:10.1177/0885066615619895 · Cited by 192 · see citing works
Composition and dynamics of the respiratory tract microbiome in intubated patients
Kelly, B. J., Imai, I., Bittinger, K. L., Laughlin, A. L., Fuchs, B. D., Bushman, F. D., & Collman, R. G. (2016) · Microbiome · doi:10.1186/s40168-016-0151-8 · Cited by 190 · see citing works
Dramatic Changes of the Gut Flora Immediately After Severe and Sudden Insults
Hayakawa, M., Asahara, T., Henzan, N., Murakami, H., Yamamoto, H., Mukai, N., Minami, Y., Sugano, M., Kubota, N., Uegaki, S., et al. (2011) · Digestive Diseases and Sciences · doi:10.1007/s10620-011-1649-3 · Cited by 160 · see citing works
Advances in antibiotic therapy in the critically ill
Vincent, J., Bassetti, M., François, B., Karam, G. H., Chastre, J. E., Torres, A., Roberts, J. A., Taccone, F. S., Rello, J., Calandra, T., et al. (2016) · Critical Care · doi:10.1186/s13054-016-1285-6 · Cited by 132 · see citing works
Antibiotic-induced gut microbiota disruption during human endotoxemia: a randomised controlled study
Lankelma, J. M., Cranendonk, D. R., Belzer, C., de Vos, A. F., de Vos, W. M., van der Poll, T., & Wiersinga, W. J. (2016) · Gut · doi:10.1136/gutjnl-2016-312132 · Cited by 94 · see citing works
β‐Lactam Antibiotics and Gastrointestinal Colonization with Vancomycin‐Resistant Enterococci
Rice, L. B., Hutton‐Thomas, R., Laktičová, V., Helfand, M. S., & Donskey, C. J. (2004) · The Journal of Infectious Diseases · doi:10.1086/382086 · Cited by 81 · see citing works
Hotterbeekx, A., Xavier, B. B., Bielen, K., Lammens, C., Moons, P., Schepens, T., Ieven, M. M., Jorens, P. G., Goossens, H., Kumar‐Singh, S., et al. (2016) · Scientific Reports · doi:10.1038/srep36507 · Cited by 64 · see citing works
The microbiome of the critically ill patient
Akrami, K., & Sweeney, D. A. (2017) · Current Opinion in Critical Care · doi:10.1097/mcc.0000000000000469 · Cited by 64 · see citing works
The emerging role of the microbiota in the ICU
Wolff, N. S., Hugenholtz, F., & Wiersinga, W. J. (2018) · Critical Care · doi:10.1186/s13054-018-1999-8 · Cited by 61 · see citing works
Ramos, J. R., Gordón, M., Villarreal, E., Frasquet, J., Sánchez, M. Á., Cerezuela, M. M., Castellanos, Á., & Ramírez, P. (2019) · Antimicrobial Resistance and Infection Control · doi:10.1186/s13756-019-0484-8 · Cited by 48 · see citing works
Kõljalg, S., Truusalu, K., Vainumäe, I., Štšepetova, J., Sepp, E., & Mikelsaar, M. (2008) · Journal of Clinical Microbiology · doi:10.1128/jcm.01419-08 · Cited by 43 · see citing works
Effect of piperacillin/tazobactam treatment on human bowel microflora
Nord, C. E., Brismar, B., Kasholm-Tengve, B., & Tunevall, G. (1993) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/31.suppl_a.61 · Cited by 38 · see citing works
Pérez‐Losada, M., Graham, R. J., Coquillette, M., Jafarey, A., Castro‐Nallar, E., Aira, M., Freishtat, R. J., & Mansbach, J. M. (2017) · PLoS ONE · doi:10.1371/journal.pone.0182520 · Cited by 38 · see citing works
Lu, W., Yu, J., Ai, Q., Liu, D., Song, C., & Li, L. (2014) · PLoS ONE · doi:10.1371/journal.pone.0087504 · Cited by 36 · see citing works
Nilsson-Ehle, I., Nord, C. E., & Ursing, B. (1985) · Scandinavian Journal of Infectious Diseases · doi:10.3109/00365548509070424 · Cited by 30 · see citing works
Luković, E., Moitra, V. K., & Freedberg, D. E. (2019) · Current Opinion in Anaesthesiology · doi:10.1097/aco.0000000000000734 · Cited by 30 · see citing works
The gut microbiota of critically ill patients: first steps in an unexplored world
Ruppé, É., Lisboa, T. C., & Barbier, F. (2018) · Intensive Care Medicine · doi:10.1007/s00134-018-5309-3 · Cited by 29 · see citing works
Ginn, A. N., Wiklendt, A. M., Gidding, H. F., George, N., O’Driscoll, J. S., Partridge, S. R., O’Toole, B. I., Perri, R. A., Faoagali, J., Gallagher, J. E., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0038719 · Cited by 25 · see citing works
Self-citationACSQHC – Australian Commission on Safety and Quality in Health Care
datasets, partners, & healthinsite (2016) · Cited by 24 · see citing works
Morrow, L. E., & Wischmeyer, P. E. (2016) · CHEST Journal · doi:10.1016/j.chest.2016.10.006 · Cited by 23 · see citing works
Venturini, C., Bowring, B. G., Fajardo-Lubian, A., Devine, C., & Iredell, J. R. (2020) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01504-20 · Cited by 23 · see citing works
Self-citationVogel, F., Ochs, H. R., Wettich, K., Kaiich, S., Nihson-Ehle, I., Odenholt, I., & Nord, C. E. (2001) · Clinical Microbiology and Infection · doi:10.1046/j.1198-743x.2001.00264.x · Cited by 19 · see citing works
Gorbachinsky, I., Sherertz, R. J., Russell, G. B., Krane, L. S., & Hodges, S. J. (2014) · Therapeutic Advances in Urology · doi:10.1177/1756287214542097 · Cited by 19 · see citing works
Venturini, C., Ginn, A. N., Wilson, B. E., Tsafnat, G., Paulsen, I. T., Partridge, S. R., & Iredell, J. R. (2018) · Intensive Care Medicine Experimental · doi:10.1186/s40635-018-0185-2 · Cited by 8 · see citing works
Self-citationMicrobiota in ICU, not only a gut problem
Alagna, L., Bandera, A., Patruno, A., Muscatello, A., Citerio, G., & Gori, A. (2019) · Intensive Care Medicine · doi:10.1007/s00134-018-05516-7 · Cited by 5 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Stein-Thoeringer, C. K., Saini, N. Y., Zamir, E., Blumenberg, V., Schubert, M.-L., Mor, U., Fante, M. A., Schmidt, S., Hayase, E., Hayase, T., et al. (2023) · Nature Medicine · doi:10.1038/s41591-023-02234-6 · Cited by 255 · see citing works
Antibiotics: From Mechanism of Action to Resistance and Beyond
Saikia, S., & Chetia, P. (2024) · Indian Journal of Microbiology · doi:10.1007/s12088-024-01285-8 · Cited by 38 · see citing works
Wang, J., Xiang, Q., Gu, S., Gu, Y., Yao, M., Huang, W., Wang, G. T., & Tang, L. (2022) · Infection and Drug Resistance · doi:10.2147/idr.s388687 · Cited by 27 · see citing works
Dumitru, I. G., Todor, S. B., Ichim, C., Helgiu, C., & Helgiu, A. (2025) · Journal of Clinical Medicine · doi:10.3390/jcm14092982 · Cited by 22 · see citing works
Biofilm Production in Intensive Care Units: Challenges and Implications
Taner, F., Baddal, B., Theodoridis, L., & Petrovski, S. (2024) · Pathogens · doi:10.3390/pathogens13110954 · Cited by 16 · see citing works
Vagus nerve-dependent effects of fluoxetine on anxiety- and depression-like behaviors in mice
Joo, M.-K., & Kim, D.-H. (2023) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2023.175862 · Cited by 16 · see citing works
Moderate and transient impact of antibiotic use on the gut microbiota in a rural Vietnamese cohort
Bich, V. T. N., Le, N. G., Barnett, D. J. M., Chan, J., van Best, N., Tran, T. D., Anh, N. T. H., Hoang, T. H., van Doorn, H. R., Wertheim, H. F. L., et al. (2022) · Scientific Reports · doi:10.1038/s41598-022-24488-9 · Cited by 13 · see citing works
Early reduction in gut microbiota diversity in critically ill patients is associated with mortality
Wozniak, H., Gaïa, N., Lazarević, V., Terrier, C. L., Beckmann, T. S., Balzani, E., Urner, M., Pugin, J., Schrenzel, J., Heidegger, C., et al. (2024) · Annals of Intensive Care · doi:10.1186/s13613-024-01407-x · Cited by 13 · see citing works
Cefaclor causes vagus nerve-mediated depression-like symptoms with gut dysbiosis in mice
Joo, M.-K., Shin, Y.-J., & Kim, D. (2023) · Scientific Reports · doi:10.1038/s41598-023-42690-1 · Cited by 11 · see citing works
Wang, J., Shi, C.-Y., & Ying, H. (2022) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2022.997368 · Cited by 10 · see citing works
Recent Insights into the Evolving Role of the Gut Microbiome in Critical Care
Lee, S., Wischmeyer, P. E., Mintz, C. D., & Serbanescu, M. A. (2024) · Critical Care Clinics · doi:10.1016/j.ccc.2024.11.002 · Cited by 11 · see citing works
Alfonso, A. Y. C., Lagares, L. M., Novič, M., Benfenati, E., Kumar, A., & Chayawan, C. (2022) · Toxicology in Vitro · doi:10.1016/j.tiv.2022.105332 · Cited by 8 · see citing works
McSorley, J. C. (2025) · Antibiotics · doi:10.3390/antibiotics14040399 · Cited by 7 · see citing works
Tigabu, A., & Leung, P. H. M. (2026) · Gut Pathogens · doi:10.1186/s13099-026-00795-8 · Cited by 6 · see citing works
Gut microbiota and its impact on critical illness
Battaglini, D., & Torres, A. (2025) · Current Opinion in Critical Care · doi:10.1097/mcc.0000000000001249 · Cited by 6 · see citing works
Consensus guidelines for antibacterial prophylaxis in patients with neutropenia
Lindsay, J., Yeoh, D. K., Teh, B. W., Reynolds, G. K., Henden, A. S., McQuilten, Z., Wheeler, M., Hamilton, A., Nelson, A. C., Nakagaki, M., et al. (2025) · Internal Medicine Journal · doi:10.1111/imj.70250 · Cited by 3 · see citing works
Ramos, J. R., & Ramírez, P. (2022) · Medicina Intensiva (English Edition) · doi:10.1016/j.medine.2022.09.004 · Cited by 5 · see citing works
Ramos, J. R., & Galleymore, P. R. (2022) · Medicina Intensiva · doi:10.1016/j.medin.2022.07.007 · Cited by 2 · see citing works
Rzewnicki, D. I., Chanderraj, R., Qian, E. T., Semler, M. W., Casey, J. D., Rice, T. W., Coopersmith, C. M., He, Y., Nuppnau, M., Prescott, H. C., et al. (2026) · American Journal of Respiratory and Critical Care Medicine · doi:10.1093/ajrccm/aamag257 · Cited by 1 · see citing works
Lee, Y. J., Lee, J. H., Cha, B., Shin, J., Kwon, K.-S., Shin, Y. W., Lee, K. H., & Lim, J. H. (2026) · Frontiers in Oncology · doi:10.3389/fonc.2026.1876788
- Authors
- Gamage, H. K. A. H., Venturini, C., Tetu, S. G., Kabir, M., Nayyar, V., Ginn, A. N., Roychoudhry, B., Thomas, L., Brown, M., Holmes, A., Partridge, S. R., Seppelt, I., Paulsen, I. T., & Iredell, J. R.
- Affiliations
- Macquarie University (AU)
- The University of Sydney (AU)
- NSW Health Pathology (AU)
- Corresponding author
- Paulsen, Ian T.
- Iredell, Jonathan R.
- ORCID
- Venue
- Scientific Reports
- Published
- 2021-03-31
- Volume
- 11
- Issue
- 1
- Pages
- 7252-7252
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC8012612
- OpenAlex
- W3148546398
- Cited by
- 20
- References
- 50
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 4 · 2023: 3 · 2022: 6
- FWCI
- 1.02
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Health and Medical Research Council (1046889)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Immunology and Microbiology › Applied Microbiology and Biotechnology › Antibiotic Use and Resistance
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Antibiotic Resistance in Bacteria
- Keywords
- third-generation cephalosporins, piperacillin-tazobactam, gut microbiota, critically ill patients, intensive care, antibiotic stewardship, fecal microbiota, Enterobacteriaceae, Enterococcaceae, microbiome diversity, antibiotic resistance, beta-lactam antibiotics
- MeSH terms
- Antimicrobial Stewardship, Piperacillin, Tazobactam Drug Combination, Adult, Animals, Cephalosporins, Enterobacteriaceae, Female, Humans, Male, RNA, Bacterial, RNA, Ribosomal, 16S, Critical Illness, Microbiota
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
