Cefdinir

Limits on what this shows

• Null findings: No cefdinir mitochondrial study located: PubMed cefdinir AND mitochondria returned a fetch error read as zero hits (inference from page behavior); a Crossref search for cefdinir mitochondrial dysfunction returned 15 items, the cefdinir ones being USP monographs and the mitochondrial ones unrelated book chapters; PubMed searches pairing cephalosporins with mitochondria returned an "Invalid form" zero-count page twice, which is a tooling failure, not a null result. Kalghatgi reports that bacteriostatic antibiotics avoided the effect [17]; cefdinir is bactericidal [1], so that does not help it.
• At-risk subgroups: None identified. No susceptibility group was retrieved for cefdinir.

Regulatory status

The cefdinir label text retrieved has no mitochondrial content; the label describes cefdinir as bactericidal [1].

Population evidence

CLASS EXTRAPOLATION, Tier C. Kalghatgi 2013 [17] (PubMed record and OpenAlex abstract read; full text blocked): in cultured mammalian cells and in C57BL/6 mice, clinically relevant doses of three bactericidal classes (quinolones, aminoglycosides, beta-lactams) caused mitochondrial dysfunction and reactive oxygen species overproduction with oxidative damage to DNA, proteins and membrane lipids; N-acetyl-L-cysteine reduced the harm and bacteriostatic antibiotics avoided it. No effect sizes are in the abstract. Cohort test: the record names only drug classes; cefdinir and every other individual drug are unnamed, and the full text (PMC3760005) returned a reCAPTCHA page, so the beta-lactam or beta-lactams actually tested could not be verified. Cefdinir is treated as not in the cohort. No human data. No cefdinir-specific mitochondrial study was found.

Mechanism

Class-level only: the authors link bactericidal antibiotics to ROS generation and mitochondrial impairment in mammalian cells [17]. A cefdinir-specific mitochondrial mechanism was not identified in any source retrieved, and none is claimed.

Counter-evidence held on record

Counter-evidence and limits The class finding is from cell culture and mice, not people. Cefdinir capsule bioavailability is 16 to 21% [1], so tissue exposure relative to the tested doses is unknown. This entry shares its single source with the Oxidative stress entry (see the Overlap map) and is kept independent of ATP production and oxygen delivery (Hard Rule 7). Framing caution Not a deficiency claim and no basis for any supplement. A theoretical class flag only.

Limits on what this shows

• Null findings: Labro: superoxide generation was unchanged and other cephalosporins did not reproduce the myeloperoxidase effect [18]. A PubMed listing for cefdinir AND oxidative returned 15 records, of which 1 (Labro) concerned a biological oxidant pathway; the rest were analytical chemistry, formulation or environmental papers, including a hepatic CYP enzyme paper (PMID 14709907) whose abstract was not opened.

Regulatory status

The cefdinir label text retrieved has no oxidative stress content [1].

Population evidence

Tier B, this drug, in vitro: Labro 1994 [18] (PubMed record abstract read; no concentrations or numbers in the abstract). In human neutrophils and cell-free systems, cefdinir inhibited luminol-amplified chemiluminescence triggered by PMA and by opsonized zymosan in cytochalasin B-treated cells, and impaired responses to A23187 and FMLP; it inhibited chemiluminescence and orthodianisidine oxidation in horseradish peroxidase and myeloperoxidase-containing neutrophil extract systems; superoxide generation and degranulation were not altered; bacterial killing was not altered at concentrations that inhibited myeloperoxidase-dependent reactions; the effect was on myeloperoxidase in the extracellular medium and not in the phagolysosome. Other cephalosporins, with or without the aminothiazolyl group, did not significantly alter the neutrophil response. CLASS EXTRAPOLATION, Tier C: Kalghatgi 2013 [17] (abstract read; cefdinir not named, drug identities unverified as described under Mitochondrial burden) found raised blood oxidative stress markers, oxidative tissue damage and upregulated antioxidant defense genes in mice given bactericidal quinolones, aminoglycosides and beta-lactams. No human oxidative stress marker (malondialdehyde, superoxide dismutase, glutathione, total antioxidant capacity) in cefdinir users was found.

Mechanism

For the in vitro finding, direct inhibition of myeloperoxidase activity [18]; the abstract does not address iron binding or heme interaction. For the class flag, ROS-linked mitochondrial dysfunction [17], as in the Mitochondrial burden entry.

Direction

Mixed and unresolved. The cefdinir-specific in vitro finding is reduction of an oxidant-generating pathway (reverse direction, protective-looking in a test tube); the class finding is increased oxidative stress. Neither is a measure of antioxidant nutrient status.

Counter-evidence held on record

Counter-evidence and limits An in vitro enzyme effect at unstated concentrations is a pharmacodynamic observation, not oxidative stress status and not a nutrient deficiency (Hard Rule 2); whether plasma or tissue cefdinir levels reach the tested concentrations is unknown. The class source is cell and mouse work with cefdinir unnamed. The two entries rest on separate sources that disagree in direction, so they cannot be added into a net effect. Framing caution Not an antioxidant depletion claim and not a benefit claim. No antioxidant supplement is supported by this entry.

Limits on what this shows

• Null findings: Iron-fortified infant formula at 2.2 mg elemental iron per 6 oz: no significant effect on cefdinir absorption [2]. The label-reported 80% and 31% reductions apply to a 60 mg iron product and a 10 mg iron vitamin, so absorption loss scales with the iron dose and product, not with the word "iron" alone. Ueno's delayed-iron arm [5] suggests exposure after the 3-hour mark can still fall, so the 2-hour label interval should be read as a minimum, not a proven threshold.
• At-risk subgroups: Anyone taking iron tablets, multivitamins with minerals or iron-containing products at the same time as cefdinir; infants on iron-supplemented formula for the stool color change. Iron-deficient people prescribed iron concurrently are the group where failed antibiotic absorption and reddish stool both matter.

Regulatory status

Label, Drug Interactions: concomitant cefdinir with a therapeutic iron supplement containing 60 mg elemental iron (as FeSO4) reduced the extent of absorption by 80%, and with vitamins containing 10 mg elemental iron by 31%; take cefdinir at least 2 hours before or after iron. Foods highly fortified with iron (mainly cereals) have not been studied. Reddish stools have been reported, often in patients also taking iron-containing products, due to a non-absorbable complex between cefdinir or its breakdown products and iron in the gut [1]. The suspension label adds that iron-fortified infant formula (2.2 mg elemental iron per 6 oz) has no significant effect and that cefdinir can be given with it [2].

Population evidence

Tier A, nutrient to drug. Ueno 1993 [5] (abstract only, via a reconstructed OpenAlex record; the abstract gives no participant number, but the Wiesner review's study table lists it as a randomized crossover of 6 participants [7]): randomized three-way crossover in healthy men, cefdinir 200 mg alone, with two iron tablets at the same time, or with iron 3 hours later. AUC(0 to 12) with simultaneous iron was 0.78 (SD 0.38) versus 10.3 (SD 1.35) ug.h/mL for cefdinir alone, a reduction of about 92%. With iron given 3 hours later, AUC(0 to 3) was unchanged but AUC(3 to 12) was 4.60 (SD 1.54) versus 8.03 (SD 1.72), a reduction of about 43%. Wiesner 2024 [7] (systematic review, 166 studies, 32 beta-lactams; abstract plus part of the journal page read through a summarizer): antacids or mineral supplements significantly lowered bioavailability for 4 of 13 analysed beta-lactams, and the abstract reports the "highest negative impact for cefdinir (with iron salts)". Its table lists three cefdinir mineral-supplement entries (Ueno 1993, randomized crossover, 6 participants; Kato 2002, randomized crossover, 9 participants; a product-label entry, 12 participants), but the pooled ratio of means with CI and the doses were not in the retrieved content. The authors rated the evidence quality low. Lancaster 2008 [6] (case report, summarized from OpenAlex, full text not opened): a 9-month-old on cefdinir with iron-supplemented formula developed nonbloody red stools that cleared after stopping and recurred on re-exposure; Naranjo score "highly probable". Al Okla 2023 [22] (case series of 3 infants, abstract read from the PubMed record): red stools after cefdinir in children already receiving iron-containing preparations, stools heme-negative, reversible on stopping cefdinir; the authors cite fewer than 10 cases in the literature. Two other red-stool case reports, Eljaaly 2020 [15] and a 2024 Cureus report, were seen as titles or metadata only and are not used. Wiesner Table 1 participant counts were re-read on the publisher page (Ueno 6, Kato 9, label entry 12); the pooled ratio of means and CI were again absent from the page text, so the pooled effect size remains not retrieved.

Mechanism

Chelation in the gut lumen. Ueno and co-authors propose a cefdinir-iron chelate that limits absorption [5], and the label describes a non-absorbable complex [1]. The same complex explains the red stool.

Direction and ceiling

Nutrient affecting the drug (Hard Rule 4), filed as a timing interaction with a separation interval, not as depletion. The reverse direction (cefdinir lowering iron absorption or ferritin) is plausible from the same complex but has no measurement in any source retrieved. That is why the entry is capped at yellow despite three Tier A drug-specific sources on the interaction itself.

Counter-evidence held on record

Counter-evidence and limits The Ueno result and the label differ in size (92% versus 80%), as expected from different iron preparations and doses; neither is a human iron-status study. Reddish stool is a color change, not iron loss. The 2023 report titled as "bloody diarrhea" [22] was opened: its stools were heme-negative, so it supports the red-stool color effect rather than true bleeding. A child with red stool on cefdinir should still have heme-negative status confirmed by a clinician rather than assumed. Framing caution This is not an iron deficiency claim and not a reason to take or stop iron. Do not skip needed iron; space it from cefdinir by at least 2 hours per the label. No iron dose is recommended here.

Limits on what this shows

• Why no grade: Dual condition met: no Tier B or C source opened and no circulating copper claim found. Not a finding of safety. Kept independent of Iron (Hard Rule 7); the cefdinir-iron complex is not evidence about copper.

What was searched

First pass: PubMed listing "cefdinir AND (copper OR zinc OR magnesium)" returned 4 records, all irrelevant to copper status. Repair pass: PubMed "cefdinir AND copper" returned 1 record (PMID 32979903, bacteria in hospital surroundings, resistant to cefdinir and tolerant of toxic metals; no cefdinir-copper interaction studied); PubMed "cefdinir AND (metal OR chelate OR complex OR zinc OR cupric)" returned 30 results (19 shown), none on copper or zinc binding or trace metal status, the metal-relevant ones being iron red-stool reports and the calcium polycarbophil study [23] (iron slowed in vitro release, calcium did not, copper untested); Crossref "cefdinir copper complex" failed twice (rate limit, then a fetch error) so was not completed. No ceruloplasmin or serum copper study with cefdinir was located. The label drug-interaction section lists antacids, probenecid and iron only [1].

Channel outcomes

PubMed listing worked for three copper or metal queries; Crossref copper search incomplete; WebSearch budget exhausted; Europe PMC, Semantic Scholar and eutils not used per the network policy. Genuine gap as far as reached, with some tooling limitation on metal-complex chemistry literature.

Limits on what this shows

• Null findings: Partial null in humans: in the 7-child fecal flora study the main flora varied little in 5 of 7 children and the authors judged the effect relatively small [19]. No study reported unchanged C. difficile infection risk on cefdinir. First-pass search for a human gut composition study: a PubMed listing for cefdinir with fecal, stool or intestinal and flora, bacteria or microbiota returned 24 records; the 10 on the first page were the mouse papers [9], an animal vesicle-delivery paper, a rat probiotic paper, and older Japanese pediatric clinical or chemistry papers by title (not opened), with no identifiable human fecal composition study of cefdinir. Pages 2 and 3 were not retrieved in the first pass; the repair search found the Japanese-language fecal flora study [19]. Repair search: a PubMed listing for cefdinir AND difficile returned 9 records, all characterized; besides [8], [19], [20] and the pyelonephritis and pediatric urinary tract infection comparisons below, the rest were unrelated. Cardinale 2023 [24] (2685 children, cefdinir vs cephalexin vs SMX-TMP for urinary tract infection) lists C. difficile infection only inside a secondary outcome with no counts in the abstract, and Miesner 2026 [25] (75 cefdinir and 135 cephalexin cases) lists it only inside a composite outcome with no counts in the abstract, so neither supplies a usable second estimate. Crossref searches for cefdinir with intestinal flora and with C. difficile risk cohort found no further human cohort naming cefdinir (a Reactions Weekly note on a case of fulminant C. difficile infection with an amoxicillin, cefdinir and tebipenem pivoxil combination was seen as a title only and not used).
• At-risk subgroups: Adults aged 65 or older with a recent hospitalization or a Charlson index of 3 or more: absolute risk about 7 times the overall cefdinir figure (42.27 versus 6.22 per 10,000) [8]. The subgroup adjusted OR from Supplementary Table S3 (supplement PDF, read through a summarizing fetch tool) was 4.18 (95% CI 2.41 to 7.24) versus doxycycline, with clindamycin 4.40 (2.85 to 6.81) and cefuroxime 3.73 (2.30 to 6.06) in the same stratum; the unadjusted OR was 4.37 (2.52 to 7.56) [8].

Regulatory status

Label warning: Clostridium difficile associated diarrhea "has been reported with use of nearly all antibacterial agents" and may range from mild diarrhea to fatal colitis [1]. The warning is class-wide, not a cefdinir-specific rate.

Population evidence

Zhang 2022 [8], abstract via a reconstructed OpenAlex record and results tables via the journal full text read through a summarizing fetch tool: retrospective cohort in the IBM MarketScan databases, 2008 to 2020, 36,626,794 adults with an outpatient antibiotic prescription, 11,607 (0.03%) developed community-acquired C. difficile infection (ICD code within 90 days). Relative to doxycycline, cefdinir had an adjusted OR of 5.86 (95% CI 5.03 to 6.83), second only to clindamycin (8.81; 7.76 to 10.00) and ahead of cefuroxime (4.57; 3.87 to 5.39) and fluoroquinolones (4.05; 3.58 to 4.59). Cefdinir-specific results (Tables 2 to 4 as relayed by the summarizer): 683,161 cefdinir prescriptions, 425 cases, absolute risk 6.22 per 10,000 prescriptions over 90 days, attributable risk 5.07 per 10,000 over doxycycline, number needed to harm 1,972; unadjusted OR 5.42 (4.65 to 6.32); adjusted for age, sex, Charlson index, region, hospitalization in the prior 90 days and other antibiotics. In the high-risk subgroup (age 65 or older with a hospitalization in the prior 90 days or Charlson index of 3 or more): 5,915 prescriptions, 25 cases, 42.27 per 10,000, number needed to harm 307. Human fecal flora data: Iwata 1992 [19] (PubMed record, English abstract read; Japanese-language journal, full text not opened): 7 children aged 6 months to 12 years 7 months given cefdinir 3.0 to 3.7 mg/kg three times daily for 4 to 14 days. Fecal Enterobacteriaceae and total anaerobe counts fell markedly in 2 of the 7 and the main flora varied little in the others; C. difficile was detected in 1 child and C. difficile D-1 antigen in 4, with no relationship to fecal character; some Enterococcus and Bacteroides showed higher resistance during or after treatment; cefdinir was recovered from the feces of 2 children at 0.99 to 254 ug/g, the highest level in a child with low fecal beta-lactamase activity and marked decreases in Enterobacteriaceae and anaerobes. The authors judged the effect on intestinal flora relatively small while advising caution because of high fecal concentrations, diarrhea and microbial replacement. The abstract describes no comparator group, so the changes are not benchmarked against non-use. Human nasopharyngeal (not gut) data: Brook and Gober 2005 [10], 50 children with otitis media, 25 per arm; after therapy the total number of bacterial isolates recovered was 36 with cefdinir versus 56 with amoxicillin (about 71 and 73 respectively before therapy, per the reconstructed abstract), and potential pathogens remained in 6 isolates (5 penicillin-resistant) with cefdinir versus 27 (16 penicillin-resistant) with amoxicillin. This shows an antibacterial effect on a human mucosal community and is supporting context only.

Mechanism

Present and Tier B in animals. Cefdinir is bactericidal by inhibiting cell wall synthesis [1]. In mice infected with Streptococcus pneumoniae, 10 days of cefaclor, cefdinir or cefixime shifted gut cocci and bacilli, reduced Bifidobacterium and Lactobacillus, and increased Enterococcus and Candida, with higher serum endotoxin and cytokines [9]. Strain, sample size and dose were not stated in the retrieved abstract, and the three cephalosporins were pooled in the abstract, so the finding is not cefdinir-only. Additional cefdinir-specific animal data (Tier B, abstracts only): in a rat toxicity study of another cephalosporin, cefdinir served as a reference compound in the 1000 mg potency/kg group (its duration was not stated in the abstract); intestinal flora were decreased at the end of dosing, and at 2 weeks of withdrawal C. difficile and its D-1 toxin were highly detected in cecal contents with inflammatory changes in the cecum and colon, with flora still elevated at 4 weeks [20]. In male Sprague-Dawley rats, cefdinir changed the total amount, types and distribution of nearly all measured fecal short-chain fatty acids during dosing and after withdrawal, more than azithromycin did; animal numbers, doses and per-SCFA values were not in the abstract [21].

Counter-evidence held on record

Counter-evidence and limits Observational, with confounding by indication (sinusitis, otitis, pharyngitis and the patients who receive them differ from those given doxycycline) and the reference drug is itself an antibiotic, so the odds ratio is a comparison between antibiotics, not against non-use. C. difficile infection is a clinical outcome, so this entry is a functional-risk finding and not a measured change in microbial composition (Hard Rule 2 spirit). Why not red: no second independent human cohort naming cefdinir for C. difficile infection, and the only human gut composition source (Iwata 1992, 7 children, no comparator) showed a marked change in 2 of 7 children and was read by its authors as a relatively small effect, so direction is consistent but sample size and magnitude do not meet the red bar. The animal sources [9][20][21] are Tier B mechanism, not independent human confirmation. Framing caution This is an infection-risk prompt, not a nutrient deficiency, and it does not recommend a probiotic or any supplement. Persistent or bloody diarrhea during or after cefdinir needs clinical assessment.

Limits on what this shows

• Null findings: None located.

Regulatory status

Label, as read through a summarizing fetch tool: "hemolytic anemia" appears in Postmarketing Experience and, with aplastic anemia, in the Cephalosporin Class Adverse Events list; cephalosporins "are known to occasionally induce a positive direct Coombs' test"; US trial laboratory changes included decreased hemoglobin at 0.3% (trial population reported by the summarizer as N=3841; denominator for the laboratory item not confirmed) [1].

Population evidence

No cohort naming cefdinir for hemolysis was retrieved. Ahmed 2025 [13], a descriptive FDA adverse event reporting analysis (reconstructed abstract, no numbers), names hemolytic anemia only in its background as a class reaction and lists diarrhea, drug hypersensitivity and rash as cefdinir's most reported events. Maquet 2024 [14], a French nationwide study of drug-induced immune hemolytic anemia, did not name cefdinir in the retrieved abstract (cefdinir is not described there; excluded cohort).

Mechanism

Immune-mediated (drug-induced antibody) hemolysis, a recognized rare reaction to beta-lactams generally; not a nutrient pathway. Whether the label's postmarketing report was immune-mediated is not stated in the retrieved text.

Counter-evidence held on record

Counter-evidence and limits Anemia is an outcome, not iron or B12 deficiency (Hard Rule 2). A 0.3% laboratory decrease without a comparator is not evidence of reduced oxygen-carrying capacity attributable to cefdinir. Oxygen delivery is kept independent of ATP production (Hard Rule 7). Framing caution An adverse-event flag for clinicians, not a nutritional finding and not a reason to supplement iron.

Limits on what this shows

• Why no grade: Dual condition met on what was opened: no Tier B or C evidence about ATP was read and no circulating claim was found. This is a disclosed gap, not a finding of safety; it is a near-yellow candidate if Kalghatgi 2013 full text shows an ATP measurement for a beta-lactam. Kept independent of Mitochondrial burden and Oxygen delivery/utilization (Hard Rule 7); the shared class source is disclosed in the Overlap map.

What was searched

First pass: an ATP-containing PubMed listing returned no cefdinir records. Repair pass: PubMed "cefdinir AND (ATP OR oxidative phosphorylation OR respiration OR bioenergetic)" returned 2 records, neither measuring ATP: a clinical-trials guide that lists cefdinir and adenosine triphosphate as names (PMID 16082422) and the rat fecal short-chain fatty acid paper [21], which mentions host energy metabolism only as background. PubMed cefdinir AND mitochondria returned an error page read as zero hits. The one possibly relevant class source, Kalghatgi 2013 [17], carries the MeSH heading Adenosine Triphosphate/metabolism, but the abstract opened reports no ATP result, cefdinir is not named, and the full text was blocked by a reCAPTCHA page, so nothing about ATP could be read. No circulating "low energy" claim for cefdinir was reached; the one consumer interaction page opened lists only a multivitamin-with-minerals timing warning [16].

Channel outcomes

PubMed listing worked for the ATP query; PMC full text blocked; Science journal page returned a fetch error; OpenAlex search and WebSearch unavailable. Probable thin literature plus a tooling-limited check on the one class source.