Cefaclor

Limits on what this shows

• Negative or null findings: PubMed "cefaclor AND (oxidative OR mitochondrial OR mitochondria OR ATP OR reactive oxygen)" (42 results, 10 read) contained no cefaclor mitochondrial study. Cephalexin, a close structural analog, produced no in vivo respiratory toxicity at the toxic dose of cephaloridine. [20][26]
• At-risk subgroups: Not defined.
• Counter-evidence on record: The cephalexin in vivo null result.

Direction

Possible mitochondrial functional impairment (class level, animal). Not a nutrient deficiency; theoretical for cefaclor.

Regulatory status

Not addressed in any cefaclor label read. [1][2][3]

Population evidence

CLASS EXTRAPOLATION. Cohort test: cefaclor is not named in any of the six records returned by a PubMed listing for cephalosporin mitochondrial respiratory toxicity; the drugs studied were cephaloglycin, cephaloridine and cephalexin (plus imipenem). Cephaloglycin reduced net succinate uptake by 70% in vivo and in vitro (Tune 1988); cephaloridine 300 mg/kg intravenously reduced succinate uptake and respiration while the same dose of cephalexin had no effect (Tune and Hsu 1990); cephalexin inhibited uptake only in vitro. Abstract-level readings; the papers were not opened. [20]

Mechanism

Named for the toxic agents: inhibition of mitochondrial uptake of anionic substrates after renal tubular accumulation. Not tested for cefaclor, which is mainly excreted unchanged in urine (60 to 85% in 8 hours) so a renal route of exposure exists [1].

Boundary

High-dose rabbit studies of agents no longer used clinically. Shares the rabbit evidence with the oxidative stress entry.

Counter-evidence held on record

Framing caution Animal class data from other drugs; it does not describe human mitochondrial function on cefaclor. Labeled class extrapolation and capped at yellow.

Limits on what this shows

• Negative or null findings: PubMed "cefaclor AND (oxidative OR mitochondrial OR mitochondria OR ATP OR reactive oxygen)" gave 42 results, 10 read: no cefaclor MDA, glutathione, SOD or catalase measurement (the others were environmental degradation chemistry, dental pastes and unrelated papers). Class level (CLASS EXTRAPOLATION, Tier C): in rabbit renal cortex cephaloridine raised malondialdehyde and conjugated dienes and cephaloglycin depleted reduced glutathione with one-fifth the oxidized glutathione of cephaloridine, while cephalexin did not reduce respiration; cefaclor was not studied (Tune 1989, abstract level) [20][26].
• At-risk subgroups: Not defined. The authors of [19] suggest relevance to patients with altered copper homeostasis; that is their inference and was not tested.
• Counter-evidence on record: The closest class analog tested in vivo (cephalexin) showed no respiratory toxicity [20].

Direction

Possible pro-oxidant chemistry in vitro. Not a nutrient deficiency, not shown in people, and not an antioxidant-capacity measurement.

Regulatory status

Not addressed in any cefaclor label read. [1][2][3]

Population evidence

None in humans. Tier B: Bozic 2018 [19], eight beta-lactams tested with Cu(2+) by UV-Vis, EPR and electrochemical methods; cefaclor reduced Cu(2+) to Cu(1+), which reacted with molecular oxygen to give hydrogen peroxide, whereas ampicillin, amoxicillin and cephalexin formed stable 1:1 copper complexes and penicillin G showed no interaction. Concentrations, rates and any cell data were not in the abstract. Read as a PubMed abstract through a summarizing fetch tool; the paper was not opened.

Mechanism

Named: copper-mediated one-electron reduction by cefaclor and re-oxidation by oxygen. Whether this occurs at physiological free copper levels is not shown.

Boundary and overlap

Abstract-level chemistry; shares the Bozic copper study with the copper entry and the rabbit class data with the mitochondrial entry (see the overlap map).

Counter-evidence held on record

Framing caution A test-tube redox reaction and class data from other drugs; it does not describe antioxidant status or any need for antioxidants in people taking cefaclor.

Limits on what this shows

• Negative or null findings: None specific to copper. No cefaclor label or monograph read contains a copper statement.
• At-risk subgroups: Not defined.
• Counter-evidence on record: No in vivo contradiction exists because no in vivo study exists.

Direction

In vitro redox interaction between the drug and copper. It is not copper depletion or excess in people.

Regulatory status

None of the three cefaclor labels read mentions copper. The consumer monograph notes cefaclor can give unusual urine glucose test results [28]; that is a laboratory artifact, not a nutrient finding. [1][2][3]

Population evidence

Tier B: Bozic 2018 [19] as above. Copper also hindered the antibacterial activity of meropenem, amoxicillin, ampicillin and ceftriaxone against E. coli and S. aureus in that study; cefaclor was not among the four named. No human or animal copper status study with cefaclor was found. PubMed "cefaclor iron" and "cefaclor carnitine OR ferritin OR zinc OR folate" listings (16 records) contained no copper measurement. [26]

Mechanism

Named: electron transfer from cefaclor to Cu(II); the product Cu(I) is reoxidized by oxygen with H2O2 formation [19].

Boundary and overlap

Single in vitro abstract, shared with the oxidative stress entry. Copper is graded here independently of iron (Hard Rule 7).

Counter-evidence held on record

Framing caution This is test-tube chemistry. It does not indicate low or high copper in people taking cefaclor, and no copper supplement or test is implied.

Limits on what this shows

• Negative or null findings: The cefaclor ER label states H2 blockers do not alter absorption and the Wiesner table has no cefaclor mineral-supplement entry; absence of a study is not evidence of no interaction.
• At-risk subgroups: People taking iron-containing products at the same time as cefaclor, by extrapolation only. Not tested.
• Counter-evidence on record: None direct.

Direction

Nutrient or supplement affects the drug (Hard Rule 4). Filed as a possible timing interaction, not an iron depletion or excess.

Regulatory status

Cefaclor capsule, suspension and ER tablet labels read mention iron only as a colorant (black iron oxide, ferrosoferric oxide in the capsule shell) and give no iron interaction. [1][2][3]

Population evidence

CLASS EXTRAPOLATION. Cohort test: the cefdinir label (Lupin) states that iron supplements and iron-containing vitamins "reduced extent of absorption by 80% and 31%, respectively" and advises separation "at least 2 hours before or after" [22]; cefaclor was not in that cohort. The 2024 Wiesner systematic review of dietary and mineral effects on beta-lactam bioavailability (166 studies, 32 drugs) reports that antacids or mineral supplements lowered bioavailability for 4 of 13 beta-lactams analyzed, and its study table lists no cefaclor mineral-supplement study [17]. PubMed "cefaclor iron" returned 6 records, all environmental chemistry, microbiology or nanoparticle papers, none measuring iron with cefaclor in people [26].

Mechanism

Not established for cefaclor. The cefdinir label text read gives no mechanism. The only cefaclor-metal chemistry found is copper redox, not iron complexation [19].

Boundary and why not higher

Class label for a different molecule; cefaclor itself untested. Iron is graded independently of copper (Hard Rule 7).

Counter-evidence held on record

Framing caution This is a possible absorption-timing question for the prescriber or pharmacist. It is not evidence that cefaclor lowers iron and no iron supplement is recommended.

Limits on what this shows

• Negative or null findings: Scand J Infect Dis 1987 [8]: 10 volunteers on cefaclor 250 mg every 8 hours for 7 days; aerobic intestinal flora unchanged, anaerobic flora changed only slightly and returned to normal within 1 week, no colonization by cefaclor-resistant organisms; cefaclor was not detected in feces; C. difficile is not mentioned in the abstract. Strasser 2020 [9]: prospective pilot of 12 infants, 7 on long-term low-dose second-generation cephalosporin prophylaxis (identified as cefaclor in the limitations section) and 5 untreated, stool sampled on days 0, 7, 14, 30 and 70; no significant differences in observed species, Shannon index, weighted UniFrac distance or short-chain fatty acids. Four large C. difficile cohorts did not report cefaclor and are Tier C for this drug and were not used for the grade: Zhang 2022 [12] (36.6 million outpatient adults; ten antibiotics listed, cefaclor not among them), Brown 2026 [13] (text read ended mid-sensitivity analysis; cefalexin OR 3.05 reported, cefaclor not in the portion read), Webb 2020 [14] (cefaclor not mentioned) and Baxter 2008 [15] (abstract only; cefaclor not named).
• At-risk subgroups: Not stratified for cefaclor. Infants aged 1 to 3 months are the only age group with grouped flora data that include cefaclor [11][9]. Hirschhorn found attack rates rose with age (P under.001) across all antibiotics [10].
• Counter-evidence on record: Two of three human stool datasets that measured flora directly found little change at usual doses [8][9], and Finegold itself found poor correlation between gastrointestinal symptoms and C. difficile [7]; the claims estimate rests on 122 exposed individuals with a wide interval and is subject to confounding by indication and healthcare exposure [6]. The label gives no cefaclor-specific incidence.

Direction

Disturbance and infection risk (an outcome entry; overgrowth and colonization). It is not a nutrient deficiency and implies no supplementation or probiotic.

Regulatory status

US labels: C. difficile-associated diarrhea "has been reported with use of nearly all antibacterial agents" and "has been reported to occur over two months after the administration of antibacterial agents"; gastrointestinal symptoms occur in about 2.5% of patients, with diarrhea 1 in 70 (capsule and suspension labels). [1][2][3]

Population evidence

Miller 2023 [6]: matched case-control study (5 controls per case by age, sex, insurance type and enrollment period) in the MarketScan commercial, Medicare and Medicaid claims data, 159,404 community-associated CDI cases and 797,020 controls; exposure in the 30 days before the index date. Cefaclor (listed as a second-generation cephalosporin in the table footnote): exposed in 62 cases and 60 controls; unadjusted OR 5.17; adjusted OR 4.16 (95% CI 2.66 to 6.52). The text calls cefaclor a "later-generation cephalosporin" with risk "comparable to first-generation cephalosporins" and does not reconcile the two labels. No cefaclor estimate is given for the 60 to 180 day sensitivity windows. Read as full text through a summarizing fetch tool. Finegold 1987 [7]: 12 healthy young men, 6 on cefaclor 250 mg three times daily for 14 days (the other 6 on cefixime); stool before treatment, on day 14 and 2 weeks after. Cefaclor mainly led to ingrowth of new flora: E. coli present in all 6 beforehand with no decrease in counts, 13 new Enterobacteriaceae strains (mostly Klebsiella, Enterobacter and Citrobacter), C. difficile absent beforehand and newly present in 3 of 6 (Results: "Ingrowth of C. difficile was noted in four subjects on cefixime and in three on cefaclor"), cytotoxin positive in only 1 of those 3 (Table 3), 2 subjects gaining S. aureus, and the abstract reports Bifidobacterium eliminated in 2 cefaclor subjects (the Results text pools both drugs: "two of five subjects with this genus present"); the B. fragilis group was present in all 6 and eliminated in none. The authors call the overall change modest, report gastrointestinal side effects as mild and infrequent with none requiring withdrawal, and note "poor correlation between the presence of gastrointestinal symptoms and the presence of C. difficile". No cefaclor P values are given (the only significant change was the E. coli decrease on cefixime, t test on log counts) and counts appear only in graphs. This is colonization and toxin detection in healthy volunteers, not clinical infection. Full text read on 2026-10-10 through a summarizing fetch tool, twice with consistent answers; Table 3 was read through the summarizer, not as a raw table. Hirschhorn 1994 [10]: retrospective HMO cohort, 51 community-acquired C. difficile-associated diarrhea cases (7.7 per 100,000 person-years), 33 cases within 42 days of 494,491 dispensed antibiotic exposures; age-adjusted attack rates were at least 10-fold higher (P under.05) for nitrofurantoin, cefuroxime, cephalexin plus dicloxacillin, ampicillin/clavulanate plus cefaclor and ampicillin/clavulanate plus cefuroxime than for ampicillin or amoxicillin. Cefaclor is in a combined group, not reported alone. Abstract only. Bennet 2002 [11]: infants aged 1 to 3 months on eight oral antibiotics including cefaclor; Bacteroides, bifidobacteria and lactobacilli were suppressed to undetectable levels in most infants on every agent except phenoxymethylpenicillin and loracarbef, with E. coli rising on cephalosporins. Cefaclor is not reported separately and group sizes were paywalled. Abstract only.

Mechanism

Named: suppression of anaerobic and commensal bacteria with outgrowth of Enterobacteriaceae and, in susceptible people, toxin-producing C. difficile (loss of colonization resistance) [7][11]. Tier B animal data with cefaclor agree on direction: oral cefaclor produced gut dysbiosis and colitis in mice [16a], reduced Bifidobacterium and Lactobacillus and raised Enterococcus, Candida and serum endotoxin in S. pneumoniae-infected mice [16b], and gave the lowest 16S OTU counts of three antibiotics in pregnant rats [16c]. Abstracts only; no doses or group sizes were visible.

Why not red

Only one cefaclor-specific C. difficile infection estimate (Miller) exists. Finegold [7] is a second, independent Tier A human dataset with cefaclor in the cohort and it points the same way (new C. difficile in 3 of 6, toxin in 1 of 6, 13 new Enterobacteriaceae strains), but it is a 6-person colonization finding with no non-use comparator and no clinical disease. The second claims cohort (Hirschhorn) pools cefaclor with amoxicillin-clavulanate. The human stool datasets disagree (Finegold ingrowth [7], versus minor change in 10 volunteers [8] and no change in 7 infants [9]), and no cefaclor study other than the claims estimate reports clinical C. difficile disease. Attempts to find a second cefaclor-specific infection cohort: Zhang, Brown, Webb, Baxter checked and negative; a PubMed "cefaclor difficile" listing (13 results, 10 read) yielded Finegold and Hirschhorn only; the pediatric Katz 2017 abstract was blocked by a reCAPTCHA page. Repair pass 2026-10-10: a PubMed listing for cefaclor with C. difficile or antibiotic-associated diarrhea (12 results, 11 with cefaclor in the abstract) again returned only Finegold and Hirschhorn as cefaclor-specific studies, plus a 2016 Balkan Med J diagnostic algorithm paper (PMID 26966622) that lists cefaclor among antibiotics used before diarrhea onset without a risk estimate (abstract level, not used); a 2020 J Pediatr pediatric case-control abstract (PMID 32171559) and a 2019 young-children case-control record name cephalosporins or antibiotics as a group, not cefaclor; a Yale thesis cohort analyzed only cefepime and ceftazidime among cephalosporins; a veteran outpatient CDI paper (PMC9614813) and a Danish general-practice case-control study could not be opened (PMC reCAPTCHA, over-long fetch URL). Tipping point: a cefaclor-alone adjusted estimate from Hirschhorn full text, or C. difficile data in the Nord volunteers, would be needed to judge whether the discordant stool studies still count against red. [26][29][33]

Boundary in the title

The orange grade covers C. difficile infection in a US insured community cohort within 30 days of cefaclor, and a stool-flora signal seen in some but not all short-course human studies; it is not a proven change in the adult gut community and not a nutrient shortfall. The label directs that diarrhea after antibiotic use be evaluated for C. difficile.

Counter-evidence held on record

Framing caution This is an infection and disturbance risk, not a nutrient deficiency. No probiotic or supplement recommendation is made or implied.

Limits on what this shows

• Why no grade: Dual condition met. (1) No Tier B or C source linking cefaclor to biotin, folate, B12 or other flora-synthesized vitamin status was found; the stool studies [7][8][9] did not measure vitamins. (2) No circulating claim: the Drugs.com interactions page lists vitamins B1, B6, B12, C, D2 and D3, zinc and coenzyme Q10 only in a "most frequently checked" list with no severity or claim, and the consumer monograph makes no vitamin claim [28]; the ODS fact sheets opened in the repair pass make none either [34]. One general consumer page on antibiotic nutrient depletion appeared in a 2026-10-10 search result list and was not opened.

Direction

Not determined.

Channels tried

PubMed "cefaclor carnitine OR cefaclor ferritin OR cefaclor zinc OR cefaclor folate" (10 records, none measuring a nutrient; one peptide-transport paper used folate as an inhibitor of ceftibuten uptake, with cefaclor only a comparator); PubMed "cefaclor AND (hypoprothrombinemia OR vitamin K OR coagulopathy OR bleeding)" (9 records); Drugs.com pages. Repair pass 2026-10-10: PubMed "cefaclor AND (biotin OR cobalamin OR folate OR thiamine OR riboflavin OR pyridoxine)" returned 5 records and the same query on the Europe PMC REST title and abstract index returned the identical 5 (two antibiotic-susceptibility panels for unusual Enterobacterales, a Serratia species study, Swedish prescribing statistics, and the ceftibuten transport paper), none measuring a B vitamin with cefaclor; PubMed "cephalosporins biotin" (9 records) and "cephalosporins vitamin B12 deficiency" (2 records) as class-level checks, none linking a cephalosporin to biotin or B12 status in people (biotin hits were bacterial biotin-ligase and probe chemistry, a cisplatin kidney protection study and a vitamin B5 and biotin pleuropericarditis case; the B12 hits were a small intestinal bacterial overgrowth review and a cephalexin absorption record with no abstract); the NIH Office of Dietary Supplements biotin, vitamin B12 and folate health-professional fact sheets were opened and contain no statement on antibiotics or cephalosporins affecting these vitamins (the biotin sheet names only anticonvulsants; the folate sheet notes colonic microbiota synthesize folate with an unclear contribution to status and names sulfasalazine only). Two more compound PubMed queries returned the home page (no results) and one simple PubMed query failed twice with fetch errors. [26][24][28][29][33][34]

Genuine gap or tooling

Now mainly a genuine gap: biotin, cobalamin and folate were searched by name on two independent indexes (PubMed and Europe PMC) with identical null results, a class-level search found nothing, and the ODS fact sheets make no antibiotic claim. Residual tooling limit: only title and abstract indexes were searched, full-text-only mentions would be missed, and no vitamin was measured in the cefaclor stool studies [7][8][9], so the absence is of measurement rather than of effect.

Counter-evidence held on record

Framing caution An ungraded entry is a disclosed absence of evidence. It is not a finding of safety.

Limits on what this shows

• Negative or null findings: The absence of cases in two PubMed listings is a limit of the search, not evidence that hemoglobin is unaffected in routine courses. The one query phrased with "Coombs" returned HTTP 429 and was not re-run.
• At-risk subgroups: Not defined by the evidence.
• Counter-evidence on record: None identified.

Direction

Adverse drug reaction (immune-mediated red-cell destruction). It is not a nutrient deficiency, not iron or B12 deficiency, and not a drug-intended effect.

Regulatory status

Capsule label: "rarely, hemolytic anemia, aplastic anemia, agranulocytosis, and reversible neutropenia of possible clinical significance"; "Pruritus, urticaria, and positive Coombs' tests each occur in less than 1 in 200 patients"; eosinophilia 1 in 50. Suspension label: positive direct Coombs tests "have been reported during treatment with the cephalosporin antibiotics"; hemolytic anemia a rare hematologic effect. ER tablet label: hemolytic anemia listed under cephalosporin-class reactions and a positive direct Coombs test under laboratory changes. [1][2][3]

Population evidence

No cohort, incidence or hemoglobin-change study with cefaclor was found. PubMed "cefaclor hemolytic anemia" returned 2 records, neither about cefaclor hemolysis (a sickle-cell outpatient fever paper with no abstract, and an in vitro verotoxin-release study). A separate listing returned Transfusion 2003 (PMID 12919436), two case reports of thrombotic thrombocytopenic purpura after cephalosporins in which cephalexin was the culprit in both and one patient had earlier TTP after cefaclor; abstract-level, a platelet and microangiopathic outcome, not used for the grade. [24][25]

Mechanism

Named in outline on labels: hypersensitivity and antibody-mediated reactions; cefaclor-specific mechanism not studied.

Boundary and why not higher

Orange would need a cohort incidence or a measured hemoglobin change in cefaclor users. A label frequency category is a regulatory estimate, not a measured effect. Anemia is an outcome here and is never filed as a nutrient finding.

Counter-evidence held on record

Framing caution Hemolysis is an uncommon allergic-type reaction to a drug. It says nothing about iron, B12 or any nutrient intake, and no supplement is indicated.

Limits on what this shows

• Negative or null findings: PubMed "cefaclor AND (mitochondria OR ATP OR membrane potential OR respiration)" returned 2 records (a metformin and Phocaeicola vulgatus paper that only proposes cefaclor as a way to suppress that bacterium, and a 1993 review of cephalosporin effects on granulocyte function); neither measured cefaclor effects on ATP or respiration. Liu 2025 (ATP, respiration and membrane potential in inner-ear cells and blood cells) tested five other antibiotic classes and no cephalosporin; Paech 2017 reduced cellular ATP with BAL30072, a monocyclic beta-lactam that is not a cephalosporin and not cefaclor. Cephalexin, the closest structural analog, did not reduce respiration in vivo at the cephaloridine toxic dose [20]. Ceftriaxone ileum respiration was unchanged [30].
• At-risk subgroups: Not defined.
• Counter-evidence on record: The cephalexin in vivo null result [20]; cefaclor is cleared mainly unchanged by the kidney with a serum half-life of 0.6 to 0.9 hour [1], and ceftriaxone is a different molecule whose tissue exposure was not compared; the ceftriaxone doses used (up to 2500 ug/mL in vitro, 15 mg/kg twice daily in rats) are not matched to cefaclor exposure.

Direction

Possible reduction in mitochondrial oxidative phosphorylation capacity (class level, animal and in vitro). Respiration is a functional surrogate for ATP output, not a measurement of it. Not a nutrient deficiency and not shown for cefaclor.

Regulatory status

Not addressed in any of the three cefaclor labels read. [1][2][3]

Population evidence

CLASS EXTRAPOLATION. Cohort test: cefaclor is in none of these studies. Barath 2022 [30] (ceftriaxone only, a third-generation cephalosporin): isolated rat liver mitochondria incubated for 1 hour with ceftriaxone 25, 250 and 2500 ug/mL gave state III (OxPhos) oxygen flux of 76.0 +/- 2.5, 66.5 +/- 5 and 63.5 +/- 4.2 pmol/s/mL against 90.8 +/- 2.7 in controls, with the respiratory control ratio at 250 ug/mL 4.2 +/- 0.2 against 5.2 +/- 0.2; in rats given ceftriaxone 15 mg/kg intraperitoneally twice daily for 3 days (n = 12 per treatment group), liver OxPhos was 245.9 +/- 11.9 against 279.0 +/- 8.3, colon OxPhos 135.9 +/- 4.2 against 170.9 +/- 10.6, and ileum showed no significant change; reported only as p under 0.05 in figure legends. ATP content and membrane potential were not found in the portion of the paper read. Browning and Lorentz 1985 [31] (cephaloglycin 200 mg/kg intravenously in rabbits, n = 6 to 10 per group): early calcium accumulation in renal cortical mitochondria with a parallel fall in succinate-supported, ADP-stimulated mitochondrial oxygen consumption; abstract only, no magnitudes visible. Tune and Fravert 1980 [32]: cephaloglycin mitochondrial toxicity persisted after isolation (abstract level, no respiration numbers). The rabbit succinate-uptake and respiration data for cephaloridine and cephalexin are recorded under mitochondrial burden [20].

Mechanism

Named for the toxic agents in the rabbit work: renal tubular accumulation, calcium overload and inhibited mitochondrial substrate uptake. Not stated for ceftriaxone in the portion read. Not tested for cefaclor.

Boundary and why not higher

Class extrapolation from other molecules, with a respiration surrogate in place of ATP, capped at yellow. Moved from ungraded on 2026-10-10 because Tier C class data with a functional energy-metabolism endpoint were found. Shares its evidence with mitochondrial burden and oxidative stress (see the overlap map).

Counter-evidence held on record

Framing caution Animal and isolated-mitochondria data from other cephalosporins; it does not describe energy production in people taking cefaclor, and no energy-related symptom or supplement is implied.