30 compounds were read against these 5 conditions; 23 produced a graded row. The other 7 are named further down.

The ranking, and the key it uses

Ordered by the best rung the compound holds anywhere in this goal; then by what that study measured; then by how many graded rows it holds here, as a tie-break only; then by name. There is no blended score — one number mixing the rung and what was measured would invent a third scale nothing was graded against. Every rung links to the rubric that assigned it.

1. 01

   Magainins

   human RCT · direct outcome · 3 graded rows across 3 of 5 conditions

   Bacterial infection · Skin infection · Antibiotic-resistant infection

   3 graded rows, 2 sources

   1. Bacterial infection

      human RCT Direct outcome Not approved for this condition

      Who was studied

      adults with mildly infected diabetic foot ulcers; randomised, double-blind, multicentre, 14 days of twice-daily topical treatment. Enrolment total not confirmed from the abstract read.

      Pexiganan, a synthetic magainin analogue, was compared as a 0.8% cream against oral ofloxacin, with clinical improvement, microbiological eradication and wound healing as endpoints; the two arms were equivalent, and later placebo-controlled phase 3 work did not show superiority over placebo. The FDA has not approved pexiganan, and no naturally occurring magainin has been tested in humans.

      Source PubMed 2 primary sources read for this row

   2. Skin infection

      human RCT Direct outcome Not approved for this condition

      Who was studied

      adults with mildly infected diabetic foot ulcers, n=835 across two double-blind randomised trials (studies 303 and 304), topical cream twice daily versus oral ofloxacin, 14 days

      The molecule tested was pexiganan (MSI-78), a synthetic 22-residue analogue of magainin 2, not a native frog magainin. Clinical improvement was 85-90% and microbiological eradication 42-47%, statistically equivalent to oral ofloxacin; study 303 failed its equivalence test. The FDA declined approval in 1999 on the grounds of no advantage over existing treatment, and a later placebo-controlled phase 3 programme (NCT01590758 / NCT01594762, OneStep-1 and -2) separated pexiganan cream from placebo on neither clinical nor microbiological response. No regulator has approved it.

      Source PubMed 2 primary sources read for this row

   3. Antibiotic-resistant infection

      in vitro Mechanistic only Not approved for this condition

      Who was studied

      109 bacterial isolates tested by CLSI broth microdilution: 46 from diabetic foot infections (including 8 MRSA) and 63 selected for resistance mechanisms - VRSA, VISA and hVISA, VanA and VanB vancomycin-resistant enterococci, ESBL-producing Enterobacteriaceae, KPC, NDM, IMP-1 and VIM-2 carbapenemase producers, and MDR Acinetobacter and Pseudomonas. No living subject.

      Recorded, and not evidence for this condition

      Pexiganan, a synthetic magainin analogue, inhibited these resistant isolates in culture with an overall MIC50 of 16 mcg/mL and MIC90 of 32 mcg/mL, with no loss of potency against the resistant phenotypes; everything here was measured in broth. Pexiganan is the one magainin taken into people, in mildly infected diabetic foot ulcers rather than in confirmed resistant infection: two phase 3 equivalence trials against oral ofloxacin led to FDA refusal in 1999 because equivalence was not superiority, and the repeat placebo-controlled phase 3 trials OneStep-1 and OneStep-2 (NCT01590758, NCT01594762) missed their primary endpoint in 2016, so it has never been approved. No study on file measured treatment of a resistant infection in an animal or a person with any magainin.

      Source PubMed Central 3 primary sources read for this row

2. 02

   Bactericidal/Permeability-Increasing Protein (BPI)

   human RCT · direct outcome · 2 graded rows across 2 of 5 conditions

   Bacterial infection · Sepsis

   2 graded rows, 2 sources

   1. Bacterial infection

      human RCT Direct outcome Not approved for this condition

      Who was studied

      children aged 2 weeks to 18 years with severe meningococcal sepsis, n=393 (190 rBPI21, 203 placebo), 22 UK and US centres, outcomes to day 60

      A recombinant N-terminal fragment, rBPI21, was given intravenously on top of standard care and the trial measured mortality, amputations and 60-day functional outcome. Mortality was 7.4% with rBPI21 and 9.9% with placebo, a difference that did not reach statistical significance (odds ratio 1.31, 95% CI 0.62-2.74, p=0.48). No regulator has approved BPI for any infection.

      Source The Lancet 1 primary source read for this row

   2. Sepsis

      human RCT Direct outcome Not approved for this condition

      Who was studied

      children aged 2 weeks to 18 years with severe meningococcal sepsis, n=393 randomised, 22 centres in the UK and USA, outcomes to day 60; enrolment predates Sepsis-3 and used clinical meningococcaemia criteria, not a SIRS or Sepsis-3 definition

      The molecule tested was rBPI21, a recombinant 21-kDa amino-terminal fragment of human BPI, not full-length BPI. This randomised placebo-controlled trial measured mortality, amputation and paediatric overall performance category, and it did not meet its primary endpoint: mortality was 7.4% with rBPI21 versus 9.9% with placebo (p=0.48), with the authors attributing the null result partly to placebo mortality far below the 25% assumed in the power calculation. No approval for sepsis exists in any jurisdiction, and the population was paediatric meningococcal sepsis only, not adult sepsis of any cause.

      Source PubMed 2 primary sources read for this row

3. 03

   Thymosin alpha-1

   human RCT · direct outcome · 2 graded rows across 2 of 5 conditions

   Sepsis · Hepatitis C

   2 graded rows, 2 sources

   1. Sepsis

      human RCT Direct outcome In registered trials

      Who was studied

      adults aged 18-85 with sepsis, n=1106 (552 thymosin alpha-1, 554 placebo), 22 centres in China, September 2016 to December 2020, 28-day follow-up; the enrolment definition is not established from the record read here

      The TESTS trial was a multicentre, double-blind, placebo-controlled phase 3 trial measuring 28-day all-cause mortality, which occurred in 23.4% of the thymosin alpha-1 group and 24.1% of placebo (hazard ratio 0.99, 95% CI 0.77 to 1.27, p=0.93), with no secondary or safety outcome differing significantly. The earlier ETASS trial (six Chinese hospitals, severe sepsis, single-blind, no placebo) reported a mortality signal that the larger blinded trial did not reproduce, and meta-analyses lose the mortality benefit when restricted to multicentre or high-quality studies. No regulator has approved thymosin alpha-1 for sepsis.

      Source PubMed 3 primary sources read for this row

   2. Hepatitis C

      human RCT Direct outcome Not approved for this condition

      Who was studied

      adults aged 18-70 with chronic hepatitis C who had not responded to prior peginterferon plus ribavirin, n=552, 48 weeks of treatment with outcome assessed at week 72; genotype not specified in the registry record; advanced (Child-Pugh B/C) cirrhosis excluded

      Studied only as an adjunct added to peginterferon alfa-2a plus ribavirin, never as primary therapy, and not approved for hepatitis C by the FDA or EMA. This double-blind phase 3 trial in prior non-responders measured sustained virological response as its primary endpoint and the published result (J Viral Hepat 2012, doi 10.1111/j.1365-2893.2011.01524.x) reported 12.7% with thymosin alpha-1 versus 10.5% with placebo, a difference that was not statistically significant (p=0.407). No trial of thymosin alpha-1 alongside modern direct-acting antivirals is on file.

      Source ClinicalTrials.gov 1 primary source read for this row

4. 04

   Boceprevir

   human RCT · direct outcome · 1 graded row across 1 of 5 conditions

   Hepatitis C

   1 graded row, 1 source

   1. Hepatitis C

      human RCT Direct outcome Not approved for this condition

      Who was studied

      previously untreated adults with chronic HCV genotype 1, n=1097 (938 non-black, 159 black), 44-48 weeks, in the phase 3 SPRINT-2 trial

      No longer marketed. Merck discontinued manufacture and distribution in the United States during 2015, and the European marketing authorisation for Victrelis was withdrawn on 29 June 2018 at the holder's request, so there is no current approval anywhere on file. In its era SPRINT-2 measured sustained virological response and found 67-68% with boceprevir added to peginterferon/ribavirin versus 40% with peginterferon/ribavirin alone in the non-black cohort, and 42-53% versus 23% in the black cohort; anaemia occurred in 49% of boceprevir recipients versus 29% of controls.

      Source PubMed Central 2 primary sources read for this row

5. 05

   Sofosbuvir

   human RCT · direct outcome · 1 graded row across 1 of 5 conditions

   Hepatitis C

   1 graded row, 1 source

   1. Hepatitis C

      human RCT Direct outcome Approved for this condition

      Who was studied

      adults with chronic HCV, genotypes 1-4; NEUTRINO enrolled n=327 treatment-naive adults (89% genotype 1, 9% genotype 4) with or without compensated cirrhosis; FUSION enrolled previously treated genotype 2/3 patients

      FDA-approved (Sovaldi, 2013) for chronic hepatitis C genotypes 1, 2, 3 and 4 in adults without cirrhosis or with compensated cirrhosis, and for genotype 2 or 3 in children aged 3 and over, always in combination regimens. The outcome measured was sustained virological response at 12 weeks: 90% (289/320) in treatment-naive genotype 1/4 patients on the 12-week peginterferon/ribavirin combination in NEUTRINO, 95% in treatment-naive genotype 2 in FISSION, and 82% in previously treated genotype 2 in FUSION.

      Source DailyMed — the FDA label 2 primary sources read for this row

6. 06

   Telaprevir

   human RCT · direct outcome · 1 graded row across 1 of 5 conditions

   Hepatitis C

   1 graded row, 1 source

   1. Hepatitis C

      human RCT Direct outcome Not approved for this condition

      Who was studied

      adults with genotype 1 chronic hepatitis C and compensated liver disease including cirrhosis, both treatment-naive (ADVANCE) and previously interferon-treated (REALIZE)

      No longer marketed. The EU authorisation for Incivo expired on 22 September 2016 because Janssen-Cilag chose not to renew it after interferon-free regimens arrived, and the US product Incivek was withdrawn in 2014, so there is no current approval on file. Sustained virological response was the registrational outcome, reported at 75% for 12 weeks of telaprevir with peginterferon/ribavirin versus 44% for peginterferon/ribavirin alone in treatment-naive genotype 1 patients in ADVANCE; the label carried warnings on serious and fatal skin reactions and on severe anaemia.

      Source EMA 2 primary sources read for this row

7. 07

   Vasopressin

   human RCT · direct outcome · 1 graded row across 1 of 5 conditions

   Sepsis

   1 graded row, 1 source

   1. Sepsis

      human RCT Direct outcome Approved for this condition

      Who was studied

      adults with septic shock already receiving at least 5 micrograms per minute of norepinephrine, n=778 (396 vasopressin, 382 norepinephrine), 28-day and 90-day mortality

      Mortality was measured. Low-dose vasopressin, 0.01 to 0.03 units per minute, did not reduce 28-day mortality against norepinephrine (35.4% versus 39.3%, P=0.26) or 90-day mortality (43.9% versus 49.6%, P=0.11), and serious adverse event rates were the same. A pre-specified stratum of less severe shock showed lower 28-day mortality on vasopressin (26.5% versus 35.7%, P=0.05), but the test for heterogeneity between strata was not significant. A second randomised trial on a different outcome was also negative: early vasopressin titrated to 0.06 units per minute did not increase kidney failure-free days against norepinephrine (PubMed 27483065; 57.0% of survivors never developed kidney failure against 59.2%, a difference of -2.3% with a confidence interval from -13.0% to 8.5%), though renal replacement therapy was used less often, 25.4% against 35.3%. Its authors state the findings do not support replacing norepinephrine as initial treatment. Vasopressin injection is approved in the United States to raise blood pressure in adults with vasodilatory shock who remain hypotensive despite fluids and catecholamines; that approval is for the blood pressure effect, not for a survival benefit. Rung set from the study's own design wording, "randomized, double-blind trial".

      Source PubMed 2 primary sources read for this row

8. 08

   LL-37 (Cathelicidin)

   human RCT · surrogate marker · 4 graded rows across 4 of 5 conditions

   Bacterial infection · Skin infection · Sepsis · Antibiotic-resistant infection

   4 graded rows, 3 sources

   1. Bacterial infection

      human RCT Surrogate marker Not approved for this condition

      Who was studied

      adults aged 18-60 with uninfected or mildly infected diabetic foot ulcers, n=25 (13 LL-37, 12 placebo), 4 weeks

      The primary endpoint was granulation tissue formation, a wound-healing measure; aerobic bacterial colony counts on the ulcer surface were a secondary measure and LL-37 did not significantly reduce them. No trial on file measured resolution of an established infection, bacterial cure, or survival with LL-37 in humans.

      Source PubMed Central 1 primary source read for this row

   2. Skin infection

      human RCT Surrogate marker Not approved for this condition

      Who was studied

      adults with diabetic foot ulcers, n=25 (13 LL-37, 12 placebo), Jakarta; 8 of the 25 ulcers were mildly infected at baseline, the rest uninfected; topical LL-37 cream 0.5 mg/g, 0.025 mL/cm2 twice weekly for 4 weeks

      Synthetic LL-37 was actually administered, which separates it from the rest of the endogenous skin peptides here. The primary endpoint was granulation index, which improved; aerobic bacterial colonisation counts from wound swabs, the infection-related measure, did not fall, and no infection-resolution endpoint such as cure of cellulitis was assessed. The trial was not designed as an infection trial and most enrolled ulcers were uninfected.

      Source PubMed Central 1 primary source read for this row

   3. Sepsis

      animal in vivo Direct outcome Not approved for this condition

      Who was studied

      male BALB/c mice, 7-10 weeks old, caecal ligation and puncture polymicrobial sepsis; LL-37 1 or 2 mcg per mouse intravenously immediately after surgery, survival followed 7 days

      Synthetic human LL-37 was administered intravenously to septic mice and survival rose from 6.7% (untreated caecal ligation and puncture) to 36.4% at the 2 mcg dose; bacterial load and IL-1beta fell. This is a mouse mortality result at a microgram-per-mouse dose, and no human trial of administered LL-37 in sepsis is on file.

      Source PubMed Central 1 primary source read for this row

   4. Antibiotic-resistant infection

      in vitro Mechanistic only Not approved for this condition

      Who was studied

      seven clinical Acinetobacter baumannii isolates, four of them multidrug-resistant; broth MIC, time-kill and biofilm assays only, no living subject

      Recorded, and not evidence for this condition

      Native human LL-37 failed to inhibit any of the seven isolates at the highest concentration tested, with MICs above 250 mcg/mL, while the comparator peptide WAM-1 inhibited them at 166-250 mcg/mL; the authors also note that human serum diminishes LL-37's antibacterial activity. This is a negative culture result, and no study on file gave LL-37 to an animal or a person with a resistant infection - the human LL-37 trials on file are in venous leg ulcers and diabetic foot ulcers and measured healing and surface colony counts, not resistant-organism cure.

      Source Oxford Academic 1 primary source read for this row

9. 09

   Lactoferricin

   human RCT · mechanistic only · 2 graded rows across 2 of 5 conditions

   Bacterial infection · Antibiotic-resistant infection

   2 graded rows, 2 sources

   1. Bacterial infection

      human RCT Mechanistic only In registered trials

      Who was studied

      healthy volunteers (sequential randomised double-blind ascending single doses 0.005-5 mg and multiple intravenous doses 0.5-5 mg), plus open-label single 5 mg intravenous doses in autologous haematopoietic stem cell transplant recipients

      Recorded, and not evidence for this condition

      The lactoferrin-derived peptide hLF1-11 was taken into humans, but this trial measured only safety and tolerability: no infection outcome - not cure, not bacterial clearance, not survival - was measured in any living subject, and reversible transaminase elevations were the main finding. No study on file shows hLF1-11 or lactoferricin treating an infection in a person.

      Source NCBI 1 primary source read for this row

   2. Antibiotic-resistant infection

      in vitro Mechanistic only Not approved for this condition

      Who was studied

      three multidrug-resistant, ESBL-producing enteroaggregative Escherichia coli clinical isolates; broth MIC/MBC, time-kill and membrane-permeation assays, plus Galleria mellonella wax moth larvae. No mammal or human subject.

      Recorded, and not evidence for this condition

      Lactoferricin (17-30), a 14-residue fragment of lactoferricin rather than the full peptide, inhibited and killed these resistant isolates at 32 microM with under 5% haemolysis at four times that concentration. What was measured was killing in broth, plus survival of infected wax moth larvae; no study on file has given lactoferricin to a mammal or a person with a resistant infection, so nothing here measured treatment of a resistant infection and the link to it is an argument from mechanism, not a result. The one lactoferrin-derived peptide taken into humans, hLF1-11, was a safety and tolerability trial that measured no infection outcome at all.

      Source PubMed Central 2 primary sources read for this row

10. 10

    Psoriasin (S100A7)

    human observational · mechanistic only · 2 graded rows across 2 of 5 conditions

    Skin infection · Bacterial infection

    2 graded rows, 2 sources

    1. Skin infection

       human observational Mechanistic only Not approved for this condition

       Who was studied

       healthy human skin, in vivo and explant, challenged with Escherichia coli; endogenous psoriasin was neutralised with a blocking antibody rather than administered; n not reported in the abstract

       Recorded, and not evidence for this condition

       This measured what the body already makes: psoriasin secreted by keratinocytes was identified as the principal E. coli-killing activity of skin, and blocking it with an antibody removed that activity. Psoriasin was never given to anyone, and no study measured whether administering it treats a skin infection. Presence at a site, or loss of it in diseased skin, is not evidence of treatment effect.

       Source PubMed 1 primary source read for this row

    2. Bacterial infection

       in vitro Mechanistic only Not approved for this condition

       Who was studied

       cell-free growth-inhibition and microdilution assays against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Listeria monocytogenes and Lactobacillus plantarum; no living subject

       Recorded, and not evidence for this condition

       Oxidised S100A7 inhibited growth of a zinc-uptake-deficient E. coli mutant, L. monocytogenes and L. plantarum but not wild-type E. coli K-12 or P. aeruginosa, consistent with metal sequestration rather than lysis. This is an endogenous epithelial protein studied where it already occurs; nothing was administered, and no study on file measured an infection outcome in an animal or a person.

       Source PubMed Central 1 primary source read for this row

11. 11

    Defensins

    animal in vivo · direct outcome · 3 graded rows across 3 of 5 conditions

    Sepsis · Bacterial infection · Antibiotic-resistant infection

    3 graded rows, 2 sources

    1. Sepsis

       animal in vivo Direct outcome Not approved for this condition

       Who was studied

       C57BL/6 wild-type mice, caecal ligation and puncture sepsis; human neutrophil peptide 1 (HNP-1) given intraperitoneally at 0.5 or 10 mg/kg six hours after sepsis onset, mortality assessed to 48 hours and beyond

       Administered human neutrophil peptide 1 worsened outcome: 80% of mice died at 10 mg/kg versus 20% at 0.5 mg/kg and 10% in controls, with more severe liver injury and disrupted liver interendothelial junctions. Defensins is a family, not one molecule - this result belongs to HNP-1 specifically, and the separate report of improved survival with rhesus theta-defensin RTD-1 concerns a different, non-human molecule. No human trial administering any defensin in sepsis is on file.

       Source PubMed Central 2 primary sources read for this row

    2. Bacterial infection

       in vitro Mechanistic only Not approved for this condition

       Who was studied

       multidrug-resistant nosocomial clinical isolates of Staphylococcus aureus, Enterococcus faecium, Pseudomonas aeruginosa, Stenotrophomonas maltophilia and Acinetobacter baumannii; bacterial cultures only, no living subject

       Recorded, and not evidence for this condition

       Human beta-defensin 3 killed these isolates in culture within about 20 minutes, and the work also documents how salt in physiological buffers blunts defensin killing. This was measured in cultures; no study on file administered a defensin to an animal or a person and measured an infection outcome, so the link to treating an infection is an argument from mechanism, not a result.

       Source PubMed Central 1 primary source read for this row

    3. Antibiotic-resistant infection

       in vitro Mechanistic only Not approved for this condition

       Who was studied

       30 multidrug-resistant nosocomial clinical isolates - six each of Staphylococcus aureus, Enterococcus faecium, Pseudomonas aeruginosa, Stenotrophomonas maltophilia and Acinetobacter baumannii, most resistant to at least three antibiotic classes; bacterial suspensions only, no living subject

       Recorded, and not evidence for this condition

       Human beta-defensin 3 killed these resistant isolates within 1-20 minutes at 4-16 mcg/mL in low-salt buffer, but at 150 mM phosphate it needed 64 mcg/mL against A. baumannii and was inactive against S. aureus, and 20% human serum abolished its killing of the Gram-negative strains - so the killing shown here does not survive body-like conditions. Defensins is a family: the one defensin actually administered in a resistant-organism-free sepsis model, human neutrophil peptide 1, made outcomes worse (80% mortality at 10 mg/kg versus 10% in controls), the favourable survival data belong to rhesus theta-defensin RTD-1, a different molecule, and the ABSSSI trial often cited here tested brilacidin, a synthetic defensin mimetic. No study on file administered a defensin to an animal or a person with a resistant infection.

       Source PubMed Central 2 primary sources read for this row

12. 12

    Bacteriocins

    animal in vivo · direct outcome · 2 graded rows across 2 of 5 conditions

    Bacterial infection · Antibiotic-resistant infection

    2 graded rows, 2 sources

    1. Bacterial infection

       animal in vivo Direct outcome Not approved for this condition

       Who was studied

       lactating Holstein cows with subclinical mastitis, n=90 (46 nisin Z, 44 untreated control), intramammary infusion of 2,500,000 IU once daily for 3 days

       Bacteriological cure was 65.2% (30 of 46) with nisin Z against 15.9% (7 of 44) spontaneous recovery in controls, with falls in milk NAGase activity and somatic cell count. Nisin Z is the only bacteriocin on file with an infection outcome measured in a living subject, and the subject was a cow; no bacteriocin has an infection outcome measured in humans.

       Source PubMed Central 1 primary source read for this row

    2. Antibiotic-resistant infection

       animal in vivo Direct outcome Not approved for this condition

       Who was studied

       female BALB/cJRj mice aged 6 weeks, 6 mm excisional dorsal wounds inoculated with luciferase-tagged Staphylococcus aureus Xen31, derived from the multidrug-resistant clinical isolate ATCC 33591; topical gel applied daily for up to 7 days

       Bacterial burden was followed as bioluminescence and fell sharply and durably after treatment with a hydroxypropyl cellulose gel, so this is an infection outcome in a living animal against a resistant strain. The gel was a combination - garvicin KS 5 mg/mL and micrococcin P1 0.1 mg/mL together with penicillin G 5 mg/mL - so the result belongs to the mixture and not to a bacteriocin alone, systemic physiology was not assessed, and no bacteriocin has an infection outcome measured in a person.

       Source PubMed Central 1 primary source read for this row

13. 13

    Cecropins

    animal in vivo · direct outcome · 2 graded rows across 2 of 5 conditions

    Bacterial infection · Antibiotic-resistant infection

    2 graded rows, 2 sources

    1. Bacterial infection

       animal in vivo Direct outcome Not approved for this condition

       Who was studied

       female C57BL/6 mice aged 6-8 weeks, lethal intraperitoneal Escherichia coli ATCC 25922 challenge; n=6 per group for survival, n=4 per group for bacterial load

       DAN2, a designed cecropin-like peptide, was given 30 minutes after challenge and measured survival and bacterial counts in blood and peritoneal fluid: all mice given 20 mg/kg survived five days against no controls surviving 12 hours. The peptide tested was an engineered analogue rather than a natural cecropin, and no cecropin has been given to a person in any study on file.

       Source PubMed Central 1 primary source read for this row

    2. Antibiotic-resistant infection

       in vitro Mechanistic only Not approved for this condition

       Who was studied

       one polymyxin B- and colistin-resistant clinical isolate of Acinetobacter baumannii (strain L1), with a susceptible reference strain D41 as comparator; broth MIC and bactericidal assays only, no living subject

       Recorded, and not evidence for this condition

       Cecropin P1 inhibited the polymyxin- and colistin-resistant isolate at 2.0 mcg per assay (2.0 microM), a concentration close to that needed for the susceptible strain, showing the resistance mechanism did not protect the organism from this peptide. That is one isolate in broth; no cecropin has been given to an animal or a person with a resistant infection in any study on file, and the mouse work in the wider cecropin literature used engineered cecropin-like analogues against susceptible strains.

       Source PubMed Central 1 primary source read for this row

14. 14

    Dermcidin

    animal in vivo · direct outcome · 2 graded rows across 2 of 5 conditions

    Bacterial infection · Skin infection

    2 graded rows, 1 source

    1. Bacterial infection

       animal in vivo Direct outcome Not approved for this condition

       Who was studied

       female BALB/c mice aged 6-8 weeks, 18-22 g, n=5 per group; 5 mm dorsal wounds infected with Acinetobacter baumannii, topical DCD-1L at 8x MIC once daily for 10 days

       Wound bacterial counts fell by 1.15, 2.80 and 5.32 log10 CFU/mL at days 1, 5 and 10 with faster wound closure - an infection endpoint, but in mice, with the peptide applied to the wound. Dermcidin is normally an endogenous sweat peptide; the human literature describes its presence and its in vitro killing, and no study on file has administered it to a person.

       Source PubMed Central 1 primary source read for this row

    2. Skin infection

       animal in vivo Direct outcome Not approved for this condition

       Who was studied

       mice with 5 mm dorsal burn wounds infected with Acinetobacter baumannii ATCC 19606; DCD-1L applied topically at 64 ug/mL (8x MIC) once daily for 10 days; group sizes and sex not reported in the abstract

       DCD-1L, the proteolytic fragment of dermcidin, was administered rather than merely measured, and bacterial burden was the outcome: reductions of 1.15, 2.80 and 5.32 log10 CFU/mL on days 1, 5 and 10, with faster wound closure. A companion catheter model reduced biofilm formation by 33-67%. All of this is mouse work; no human study administering dermcidin or DCD-1L for a skin infection is on file.

       Source PubMed Central 1 primary source read for this row

15. 15

    Melittin

    animal in vivo · direct outcome · 2 graded rows across 2 of 5 conditions

    Bacterial infection · Antibiotic-resistant infection

    2 graded rows, 1 source

    1. Bacterial infection

       animal in vivo Direct outcome Not approved for this condition

       Who was studied

       immunosuppressed BALB/c mice with peritoneal infection by extensively drug-resistant Acinetobacter baumannii, MRSA, or KPC-producing Klebsiella pneumoniae; repeated sub-lethal melittin doses of 2.4 mg/kg

       Melittin inhibited all three pathogens in culture (MIC 8-32 ug/mL), but in infected mice repeated dosing at the highest tolerated level showed no benefit on survival or peritoneal bacterial load. The limit was toxicity: haemolysis HD50 was 0.44 ug/mL and the murine LD50 was 4.98 mg/kg, so the concentrations that kill bacteria in a dish are not reachable in a living animal.

       Source PubMed Central 1 primary source read for this row

    2. Antibiotic-resistant infection

       animal in vivo Direct outcome Not approved for this condition

       Who was studied

       immunosuppressed BALB/c mice with peritoneal infection by extensively drug-resistant Acinetobacter baumannii, MRSA, or KPC-producing Klebsiella pneumoniae; melittin 2.4 mg/kg intraperitoneally every 12 hours, the highest sub-lethal dose

       Melittin inhibited all three resistant pathogens in culture (MIC 8-16 mcg/mL for XDR A. baumannii, 8-32 for MRSA, 32 for KPC-producing K. pneumoniae), but in infected mice repeated dosing changed neither survival nor peritoneal bacterial load, while colistin and vancomycin did. The limit is toxicity: 50% haemolysis occurred at 0.44 mcg/mL and the intraperitoneal LD50 in mice was 4.95 mg/kg, so the concentrations that kill these organisms in a dish cannot be reached in a living animal.

       Source PubMed Central 1 primary source read for this row

16. 16

    Nisin

    animal in vivo · direct outcome · 2 graded rows across 2 of 5 conditions

    Bacterial infection · Antibiotic-resistant infection

    2 graded rows, 2 sources

    1. Bacterial infection

       animal in vivo Direct outcome Not approved for this condition

       Who was studied

       lactating dairy cows with clinical mastitis, intramammary nisin compared with gentamicin

       Clinical cure was 90.2% with intramammary nisin and 91.1% with gentamicin, with bacteriological cure of 60.8% and 44.6% respectively - an infection endpoint, but in cattle udders, by direct infusion. Nisin's long safety record as a food preservative is a food-additive record and is not evidence that it treats infection in a person; no human infection trial is on file.

       Source PubMed 1 primary source read for this row

    2. Antibiotic-resistant infection

       in vitro Mechanistic only Not approved for this condition

       Who was studied

       106 staphylococcal isolates from periprosthetic joint infection, including 26 MRSA and 27 methicillin-resistant Staphylococcus epidermidis; broth microdilution only, no living subject

       Recorded, and not evidence for this condition

       Native nisin A inhibited the methicillin-resistant subsets in culture at MIC50 4 and MIC90 8 mcg/mL for MRSA, and MIC50 2 and MIC90 4 mcg/mL for methicillin-resistant S. epidermidis. This was measured in broth against isolates taken from patients, not in patients; no study on file gave nisin to an animal or a person with a resistant infection, and nisin's long record as a food preservative is a food-additive safety record, not evidence of treating infection.

       Source PubMed Central 1 primary source read for this row

17. 17

    Proline-rich Antimicrobial Peptides (PrAMPs)

    animal in vivo · direct outcome · 2 graded rows across 2 of 5 conditions

    Bacterial infection · Antibiotic-resistant infection

    2 graded rows, 2 sources

    1. Bacterial infection

       animal in vivo Direct outcome Not approved for this condition

       Who was studied

       mice with systemic Salmonella typhimurium infection treated with Bac7(1-35) at 30 mg/kg

       The bovine proline-rich peptide Bac7(1-35) measured survival and organ bacterial load, raising mean survival from 10 days in untreated controls to 24.5 days, with rapid renal clearance limiting the effect. This is a mouse result; no proline-rich antimicrobial peptide has an infection outcome measured in humans on file.

       Source NCBI 1 primary source read for this row

    2. Antibiotic-resistant infection

       animal in vivo Direct outcome Not approved for this condition

       Who was studied

       mice with bacteraemia caused by multidrug-resistant Acinetobacter baumannii HUMC1, 6-8 animals per group; ARV-1502 given intravenously at 1.25, 2.5 or 5.0 mg/kg twice daily for 3 days

       Survival and tissue bacterial density were both measured: all ARV-1502 monotherapy groups survived while untreated animals and those given imipenem/cilastatin alone all died, with dose-dependent falls in organ bacterial counts and no systemic toxicity noted. ARV-1502 is an engineered analogue of the insect proline-rich peptides drosocin and pyrrhocoricin, not a natural PrAMP; the natural members - Bac7(1-35), oncocin Onc72, Api137 - have in vivo results only against antibiotic-susceptible strains, and no PrAMP has been given to a person with a resistant infection in any study on file.

       Source PubMed Central 2 primary sources read for this row

18. 18

    Temporins

    animal in vivo · direct outcome · 2 graded rows across 2 of 5 conditions

    Bacterial infection · Antibiotic-resistant infection

    2 graded rows, 2 sources

    1. Bacterial infection

       animal in vivo Direct outcome Not approved for this condition

       Who was studied

       female BALB/c mice aged 8-10 weeks, systemic Staphylococcus aureus A170 and Salmonella enterica serovar Paratyphi infection models, immediate and delayed (day 7) treatment

       Temporin A combined with a modified temporin B measured survival and bacterial load in kidneys, liver and gut: treated mice survived to day 28 while untreated mice died within 4-6 days, and organs were cleared within 3-6 days. All of this is in mice; no temporin has been given to a person in any study on file.

       Source PubMed Central 1 primary source read for this row

    2. Antibiotic-resistant infection

       in vitro Mechanistic only Not approved for this condition

       Who was studied

       20 carbapenemase-producing Klebsiella pneumoniae clinical isolates, KPC and metallo-beta-lactamase producers, plus reference strains; broth MIC assays only, no living subject

       Recorded, and not evidence for this condition

       The peptide that inhibited these carbapenem-resistant isolates at 6.25-25 microM was a lipidated temporin L analogue, and native unmodified temporin L was not tested in this work, so the result belongs to the analogue rather than to a natural temporin. Everything was measured in broth: no study on file gave any temporin, native or modified, to an animal or a person with a resistant infection.

       Source PubMed Central 2 primary sources read for this row

19. 19

    Adrenomedullin

    animal in vivo · direct outcome · 1 graded row across 1 of 5 conditions

    Sepsis

    1 graded row, 1 source

    1. Sepsis

       animal in vivo Direct outcome Not approved for this condition

       Who was studied

       BALB/c and C57BL/6 mice, 6-8 weeks old, LPS endotoxaemia and caecal ligation and puncture models; adrenomedullin given intraperitoneally at 0.05-5.0 nmol per mouse (about 6-550 mcg/kg), survival followed 96 hours to 10 days

       The only administration-and-mortality evidence on file is in mice: intraperitoneal adrenomedullin reduced lethality in LPS endotoxaemia and caecal ligation and puncture. The large human adrenomedullin literature in sepsis is not interventional - bio-ADM is measured as a prognostic marker of mortality and organ failure in septic patients, which is observational biology about a molecule the body already makes and is not evidence that giving adrenomedullin treats sepsis. The AdrenOSS-2 phase 2a trial (n=301, septic shock) tested adrecizumab, a non-neutralising anti-adrenomedullin antibody, which is a different intervention; it reported no difference in 90-day mortality, and in any case evidence about the antibody is not evidence about the peptide.

       Source PubMed Central 3 primary sources read for this row

20. 20

    Hyaluronic Acid Binding Peptide

    animal in vivo · direct outcome · 1 graded row across 1 of 5 conditions

    Skin infection

    1 graded row, 1 source

    1. Skin infection

       animal in vivo Direct outcome Not approved for this condition

       Who was studied

       Mice in a surgical wound infection model challenged with methicillin-susceptible and methicillin-resistant Staphylococcus aureus, given the hyaluronic acid-binding peptide PEP35 at onset of infection and up to four hours after

       PEP35 had no direct antimicrobial activity against any isolate tested, and still reduced bacterial burden at the wound site by recruiting neutrophils faster through local CXCL1 and CXCL2 production. Note that PEP35 and the cartilage-coating peptide above are different sequences sharing one generic name; a reader should not treat the two rows as evidence about one molecule. No human study exists for either. Rung set from the study's own design wording, "murine".

       Source PubMed 9 primary sources read for this row

21. 21

    Urocortin

    animal in vivo · direct outcome · 1 graded row across 1 of 5 conditions

    Sepsis

    1 graded row, 1 source

    1. Sepsis

       animal in vivo Direct outcome Not approved for this condition

       Who was studied

       BALB/c and C57BL/6 mice, 6-8 weeks old, LPS endotoxaemia and caecal ligation and puncture models; urocortin 1 given intraperitoneally at 0.05-5.0 nmol per mouse (about 6-550 mcg/kg), survival followed 96 hours (LPS) and 8-10 days (CLP)

       Urocortin 1 was administered to mice after LPS challenge or caecal ligation and puncture and reduced lethality, alongside falls in TNF-alpha, IL-6, IL-1beta and nitric oxide. Mortality in rodents is the outcome measured; no human study administering urocortin in sepsis is on file, and no regulator has approved it for any condition.

       Source PubMed Central 1 primary source read for this row

22. 22

    RNase 7

    in vitro · mechanistic only · 2 graded rows across 2 of 5 conditions

    Bacterial infection · Skin infection

    2 graded rows, 2 sources

    1. Bacterial infection

       in vitro Mechanistic only Not approved for this condition

       Who was studied

       cultures of Enterococcus faecium and other skin organisms, plus human skin extracts treated with an anti-RNase 7 antibody; no living subject

       Recorded, and not evidence for this condition

       Skin-derived RNase 7 killed E. faecium in culture independently of its ribonuclease activity, and blocking it with an antibody reduced the killing capacity of skin extracts. That is observational biology about a protein the skin already makes; no study on file administered RNase 7 to an animal or a person, and no infection outcome was measured in a living subject.

       Source PubMed Central 1 primary source read for this row

    2. Skin infection

       in vitro Mechanistic only Not approved for this condition

       Who was studied

       human primary keratinocytes, 3D organotypic skin equivalents and stratum corneum extracts, challenged with Corynebacterium amycolatum and C. xerosis; no human or animal subjects

       Recorded, and not evidence for this condition

       Recombinant RNase 7 inhibited bacterial growth in culture dose-dependently, and neutralising endogenous RNase 7 in stratum corneum extracts allowed bacterial outgrowth. Both are bench measurements of skin-surface biology; no study administered RNase 7 to a person or an animal, and no clinical skin infection outcome such as impetigo, infected ulcer or surgical site infection has been measured.

       Source PubMed Central 1 primary source read for this row

23. 23

    PGLa

    in vitro · mechanistic only · 1 graded row across 1 of 5 conditions

    Bacterial infection

    1 graded row, 1 source

    1. Bacterial infection

       in vitro Mechanistic only Not approved for this condition

       Who was studied

       Escherichia coli K12 cultures and model lipid bilayers; no living subject

       Recorded, and not evidence for this condition

       Equimolar PGLa with magainin 2 lowered the minimum inhibitory concentration against E. coli K12 by roughly tenfold, and the work traces this to a heterodimer forming in the membrane. Everything here was measured in culture and in synthetic membranes; no study on file gave PGLa to an animal or a person and measured an infection outcome.

       Source PubMed Central 1 primary source read for this row

Checked, and nothing on file

7 compounds were read against these conditions and produced no gradeable row. They are named here rather than left off, because a list of 23 reads identically whether 23 survived 30 or 23 were all anyone thought of.

1. Angiotensin I on sepsis

   No rung — nothing on file to grade Not approved for this condition

   The vasopressor trialled and licensed in vasodilatory shock is angiotensin II, a different compound. No study administers angiotensin I in shock, and it would be a poor choice: its conversion depends on pulmonary converting-enzyme activity, which is itself impaired in critical illness, so the delivered dose would be unpredictable.

2. C-Max

   No rung — nothing on file to grade

   Checked against bacterial infection. No study meeting the rubric was found for any of them.

3. Enfuvirtide on bacterial infection

   No rung — nothing on file to grade Not approved for this condition

   Enfuvirtide is a viral fusion inhibitor specific to HIV-1 gp41 and has no antibacterial activity; no study has tested it against a bacterial infection.

4. Enfuvirtide on antibiotic-resistant infection

   No rung — nothing on file to grade Not approved for this condition

   Same reason: no antibacterial mechanism and no study.

5. Enfuvirtide on hepatitis c

   No rung — nothing on file to grade Not approved for this condition

   Enfuvirtide appears in HIV/HCV co-infection cohorts as background antiretroviral therapy. No study has measured an HCV outcome attributable to it, and its mechanism, blocking HIV-1 gp41-mediated fusion, does not act on HCV.

6. Histatins

   No rung — nothing on file to grade

   Checked against bacterial infection, skin infection. No study meeting the rubric was found for any of them.

7. IGF-1 on sepsis

   No rung — nothing on file to grade Not approved for this condition

   IGF-I appears in critical-illness reviews alongside growth hormone, but no trial retrieved administered IGF-I to a septic population with a mortality or organ-failure endpoint. The large critical-illness mortality signal reported in that literature belongs to growth hormone, and must not be read across.

8. Simonson Alpha 1

   No rung — nothing on file to grade

   Checked against bacterial infection. No study meeting the rubric was found for any of them.

9. Thymopentin

   No rung — nothing on file to grade

   Checked against hepatitis c. No study meeting the rubric was found for any of them.

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