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Short answer: Caveats apply to how IV (intravenous) antibiotics might influence gut microbiota,

  • Antibiotics are usually oral (peroral to be precise). Far from the norm, IV antibiotics are usually given
    • To seriously ill, usually hospitalized, people strongly suspected of having systemic bacterial infection or
    • As a precaution to patients about to undergo invasive surgery or
    • To severely ill newborns.
  • When given to the seriously ill, how to decipher if changes to gut microbiota were because the antibiotics were given IV or because the person was really sick to start with?
  • When given to severely ill newborns, is the IV antibiotic effect, whatever it may be, due to route or age?
  • Dose, another important difference, also influences how oral versus IV antibiotics could influence gut microbiota.

Study of human microbiota is in its infancy and using modern molecular biological tools to study how antibiotics affect it is of even more recent vintage. Many older studies have examined how oral antibiotics change gut microbiota but far fewer what happens after IV antibiotics. The following summarizes key features and findings of some of the few such studies as of 2016. Again, there are caveats.

  • Many are old studies that assessed change by looking at what grew out in bacterial cultures, something we now know misses accounting for the bulk of gut microbiota.
  • Some studies were observational, not randomized controlled clinical trials, i.e., subject to design bias.
  • Some were randomized, prospective clinical trials on small numbers of healthy volunteers given IV antibiotics or not.
  • None of the studies compared changes in gut microbiota of healthy people after either oral or IV antibiotics versus no antibiotics, which would be a more definitive experiment.
  • All studies but one, 3 each on sick (1, 3, 4) and healthy (5, 6, 7) people, found profound, transient to long-term changes in gut microbiota. The exception (8) was for GSK1322322, a new antibiotic.

Thus, existing human data suggest IV antibiotics tested so far (Piperacillin, Tazobactam, Ampicillin, Gentamicin, Cefazolin, Meropenem, Ciprofloxacin) don’t spare gut microbiota.

Longer answer for those interested

Intravenous (IV) Antibiotics Alter Gut Microbiota In Sick People

Long before human microbiota became a separate field of study, a 1993 Swedish study (1) found IV Piperacillin/Tazobactam reduced the numbers of Bifidobacteria, Clostridia, Enterobacteria, Eubacteria, Lactobacilli, and anaerobic Gram-positive cocci (see below from 2). Fourteen men and 6 women hospitalized for intra-abdominal infections were treated for 4 to 8 days with Piperacillin (4 grams) and Tazobactam (500mg) every 8 hours by IV for 30 minutes.

Caveat to the study: We now know assessing gut microbiota by culture misses the vast majority of gut microbiota since most aren’t yet cultivable. As well, if some bacteria grew from pre- but not post- antibiotic Rx stool samples, it could be because antibiotics altered their physiology such that they no longer grew on the culture media used, i.e., the same microbes were still present but just didn’t grow in the culture medium researchers used. Combining culture plus molecular biology would give a more definitive result.

A 2012 Irish study gave IV antibiotics to sick newborns and observed how their gut microbiota changed compared to that of similarly aged untreated healthy newborns (3). Nine newborns who got parenteral (presumably IV) Ampicillin and Gentamicin within 48 hours of birth had alterations in their gut microbiota assessed using 16S ribosomal RNA analysis.

  • Four weeks after antibiotic Rx was stopped, compared to non-antibiotic Rx healthy infants (n=9), these infants had
    • Significantly higher proportions of Proteobacteria.
    • Significantly lower proportions of Actinobacteria, including Bifidobacteria and Lactobacillus.
  • Eight weeks after antibiotic Rx was stopped,
    • Significantly higher proportions of Proteobacteria remained.
    • Actinobacteria, including Bifidobacteria and Lactobacillus, levels were similar to those in untreated infants. However, the number of Bifidobacterium species was reduced.
  • Implications? Given their health benefits, Bifidobacteria and Lactobacillus reduction could have long-term effects.

An observational 2012 German-Spanish study (4) on a 68 year old man hospitalized for an infected cardiac pacemaker and treated with IV Cefazolin for 14 days found dramatic changes in gut microbiota composition using 16S rRNA and rDNA analysis. Researchers collected stool samples before, during and 40 days post-Rx.

  • Firmicutes dominated before and during start of Rx but by day 11 of Rx, biodiversity collapsed and Firmicutes was displaced by Bacteroidetes (Bacteroides and Parabacteroides genera).
  • However, 40 days after Rx stopped, total and active intestinal bacterial composition were similar to the pre-Rx state.

Researchers also analyzed the intestinal microbiota using proteomics and metabolomics.

  • By day 6 of IV antibiotics, major metabolic changes appeared. Intestinal microbiota activated drug-detoxifying mechanisms to avoid the anti-microbial effects of the antibiotics. They started expressing beta-lactamases and multi-drug efflux pumps, and reduced the metabolism and transport of bile acids, cholesterol, hormones and vitamins.

Intravenous (IV) Antibiotics Alter Gut Microbiota In Healthy People

In a 1991 Norwegian study (5), 10 healthy young adult men got 500mg of IV Meropenem over 30 minutes 3 times daily for 7 days. Researchers collected stool samples before, during (days 2, 4, 7) and 2, 4, 7, 14 days post-Rx.

  • Bacteroides, Clostridia, Enterobacteria, Streptococci and Gram-negative cocci decreased during Rx while Enterococci increased (see below from 2).
  • Intestinal flora returned to normal within 2 weeks post-Rx.
  • Caveat to the study: Bacterial changes were assessed by culture, which we now know misses the vast majority of gut microbiota since most aren’t yet cultivable.

In a 1997 randomized German study (6), 16 healthy, young adult men and women got 400mg of IV Ciprofloxacin over 60 minutes every 12 hours for 4 days. Researchers collected stool samples before, during (every day) and post-Rx (see below from 2).

  • In all volunteers, Enterobacteriaceae counts decreased.
  • Enterococci and Lactobacilli remained unchanged.
  • Caveat to the study: Bacterial changes were assessed by culture, which we now know misses the vast majority of gut microbiota since most aren’t yet cultivable.

In a 2002 French study (7) on 24 healthy young adult men, 20 got IV Quinupristin /Dalfopristin 7.5mg/kg for 5 days in 500ml infusions over 1 hour every 12 hours while 4 got placebo infusions. Researchers collected stool samples before, at the end of (day 6) and post-Rx. During treatment

  • Anaerobes (sporulating and Gram-negative bacteria) decreased slightly.
  • Enterobacteriaceae and Enterococci increased significantly.
  • Anaerobes and Enterococci resistant to erythromycin and Quinupristin/Dalfopristin increased significantly.
  • Changes disappeared within 12 weeks of post-Rx.
  • Caveat to the study: Bacterial changes were assessed by culture, which we now know misses the vast majority of gut microbiota since most aren’t yet cultivable.

A New Intravenous (IV) Antibiotic Doesn’t Alter Gut Microbiota In Healthy People

In a 2015 US Phase I randomized, double-blinded, placebo-controlled study, 62 healthy volunteers got either placebo, IV-only or repeat oral-IV dosing of a new antibiotic, GSK1322322, for 5 to 6 days (8). Researchers collected stool samples before and post-Rx. 16S rRNA analysis showed

  • Oral-IV Rx yielded significant decreases in Firmicutes and Bacteroides and increases in Betaproteobacteria, Gammaproteobacteria and Bifidobacteriaceae.
  • IV-only was similar to placebo, no significant changes in relative abundance of GI tract OTU (Operational taxonomic unit) between pre- and post-study stool samples.

Bibliography

1. Nord, C. E., et al. “Effect of piperacillin/tazobactam treatment on human bowel microflora.” Journal of Antimicrobial Chemotherapy 31.suppl A (1993): 61-65.

2. Sullivan, Åsa, Charlotta Edlund, and Carl Erik Nord. “Effect of antimicrobial agents on the ecological balance of human microflora.” The Lancet infectious diseases 1.2 (2001): 101-114.

3. Fouhy, Fiona, et al. “High-throughput sequencing reveals the incomplete, short-term recovery of infant gut microbiota following parenteral antibiotic treatment with ampicillin and gentamicin.” Antimicrobial agents and chemotherapy 56.11 (2012): 5811-5820. High-Throughput Sequencing Reveals the Incomplete, Short-Term Recovery of Infant Gut Microbiota following Parenteral Antibiotic Treatment with Ampicillin and Gentamicin

4. Pérez-Cobas, Ana Elena, et al. “Gut microbiota disturbance during antibiotic therapy: a multi-omic approach.” Gut 62.11 (2013): 1591-1601. a multi-omic approach

5. Bergan, T., C. E. Nord, and S. B. Thorsteinsson. “Effect of meropenem on the intestinal microflora.” European Journal of Clinical Microbiology and Infectious Diseases 10.6 (1991): 524-527.

6. Krueger, W. A., G. Ruckdeschel, and K. Unertl. “Influence of intravenously administered ciprofloxacin on aerobic intestinal microflora and fecal drug levels when administered simultaneously with sucralfate.” Antimicrobial agents and chemotherapy 41.8 (1997): 1725-1730. Influence of intravenously administered ciprofloxacin on aerobic intestinal microflora and fecal drug levels when administered simultaneously with sucralfate.

7. Scanvic-Hameg, A., et al. “Impact of quinupristin/dalfopristin (RP59500) on the faecal microflora in healthy volunteers.” Journal of Antimicrobial Chemotherapy 49.1 (2002): 135-139. Impact of quinupristin/dalfopristin (RP59500) on the faecal microflora in healthy volunteers

8. Arat, Seda, et al. “Microbiome changes in healthy volunteers treated with GSK1322322, a novel antibiotic targeting bacterial peptide deformylase.” Antimicrobial agents and chemotherapy 59.2 (2015): 1182-1192. Microbiome Changes in Healthy Volunteers Treated with GSK1322322, a Novel Antibiotic Targeting Bacterial Peptide Deformylase

https://www.quora.com/Do-IV-antibiotics-spare-the-gut-microbiome/answer/Tirumalai-Kamala

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