This page shows what was measured, who it was measured in, and what that does not settle.
What Cefepime does in the body
Serious hospital infections, including pneumonia and infection during very low white-cell counts.
Cefepime carries a positive and a negative charge at the same time, which lets it slip through the pores in a Gram-negative bacterium’s outer skin far faster than older cephalosporins. Once inside, it jams the tools the bacterium uses to build its wall, and the cell bursts. It is shaped so that one common family of bacterial defence enzymes cannot destroy it. Its own weakness is that it is cleared by the kidneys, and when it builds up it reaches the brain.
What happened in people
Kidney harm matched another common hospital antibiotic. Patients spent more time confused or unconscious.
✓ Reviewed first-read answer
Where this came from
A person wrote this and a reviewer approved it against this exact record. It carries no effect size.
A reviewer approved this against this record. The reviewed-claim record carrying the exact population and effect size does not exist yet.
No source is stored against this line.
The limit that matters most
Earlier database studies could not separate kidney risk from differences between the patients receiving each drug.
Where it acts
The bacterial cell envelope. In humans the organ that matters most for its harms is the brain, where accumulation produces encephalopathy and non-convulsive seizures.
Kind of result
The kind of result is not recorded
Supervision
RNAWiki has not recorded a supervision or regulatory status for this substance.
What the registries record it as
The substance registry classes this as chemical.
FDA substance registry · I8X1O0607P · read 2026-08-29
Where each sentence above came from
No recorded sentence describes the change this makes in a way that stands on its own. The page opens with what it is taken for instead, and the recorded explanation follows below.
Shown as the opening line on this page.
The limit a reviewer approved as the one that matters most here.
The four opening statements run to 110 words.
Words this page uses
Four words worth knowing first
Chosen from what this page shows, with each one explained before the word it depends on.
Comparator
A comparator is whatever the treatment was measured against.
A picture of it, and where the picture fails
It is like the other runner in a race.
Where that stops being true. A race has one winner. A study can show both arms improved.
What people get wrong. Results are read without asking what the other group got. Beating nothing is not beating a treatment.
The control condition against which the experimental intervention is assessed.
Randomisation
Randomisation means chance decides who gets which treatment.
A picture of it, and where the picture fails
It is like a coin toss deciding the groups.
Where that stops being true. A coin toss is fair once. Fairness here comes from doing it for everyone.
What people get wrong. It is thought to make groups identical. It makes them similar on average, including on things nobody measured.
Allocation of participants to arms by a chance process, so that unmeasured factors are balanced in expectation.
Absolute difference
An absolute difference is how many more people in a hundred were affected.
A picture of it, and where the picture fails
It is like counting heads in two rooms of a hundred.
Where that stops being true. Heads are easy to count. Study results carry a margin of error too.
What people get wrong. It is confused with a percentage change, which can look far larger.
The arithmetic difference in event rates between arms.
Confidence interval
A confidence interval is the range the true answer is likely to sit in.
A picture of it, and where the picture fails
It is like a weather forecast giving a range rather than one number.
Where that stops being true. A forecast range covers tomorrow. This one covers what the study could resolve.
What people get wrong. The middle number is read as the answer. A range crossing zero means no change is still possible.
An interval estimate that would contain the true parameter in a stated proportion of repeated studies.
What happened in people◇Read from sources, not yet reviewed
What happened in people
Each card is one study: the exact question it asked, who was in it, and whether it showed what it set out to show.
Highest stage of acute kidney injury or death by day 14, on a five-level ordinal scale
Odds ratio 0.95 (95% CI 0.80 to 1.13), P=.56 — no difference detected
Repeated elsewhere
Unreplicated
What this does not prove. A study that did not show an effect does not show that no effect exists anywhere.
The limits of this study, and where it came from
Main limit. The trial found what it was not looking for: days alive and free of delirium and coma were fewer with cefepime, odds ratio 0.79 (95% CI 0.65 to 0.95). It was run at a single academic centre, 94.7% of enrolment was in the emergency department, and 77.2% of participants were receiving vancomycin, so it tests the combination in practice rather than either drug alone.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Intravenous infusion or intramuscular injection, supplied as cefepime hydrochloride with L-arginine
Interval reported. 95% CI 0
Written into the record, not signed off as a reviewed claim.
30-day all-cause mortality, cefepime against other antibacterials
✓ The study showed what it set out to show
Who was studied
FDA cefepime mortality meta-analysis (88 trials, trial- and patient-level)
How many people
17755
Study design
Regulatory meta-analysis of published and unpublished randomised trials
Compared against
Not recorded for this study
Kind of result
Living longer, or avoiding a major event
What was found
Trial level 6.21% against 6.00%, adjusted risk difference 5.38 per 1,000 (95% CI -1.53 to 12.28); patient level 5.63% against 5.68%, 4.83 per 1,000 (95% CI -4.72 to 14.38)
Repeated elsewhere
Partially Replicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. This analysis is the answer to a published meta-analysis that reached the opposite conclusion from the same literature. It was performed by the regulator with access to unpublished trials, which is both its strength and the reason it cannot be independently reproduced from public data.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Intravenous infusion or intramuscular injection, supplied as cefepime hydrochloride with L-arginine
Interval reported. 95% CI -1
Written into the record, not signed off as a reviewed claim.
RNAWiki holds 2 written-up human studies for this substance, each with the question it asked.
How we know it
Each card names the study, the number of people and what the study set out to measure.
What this does not prove
These summaries were written by a person and have not been signed off as reviewed claims.
Why it matters
A study that failed is as informative as one that worked, and both are here.
What we still do not know
No reviewed claim exists, so no exact population, effect size or interval is published yet.
What it changes in the body◇Read from sources, not yet reviewed
The path through the body
From what a person takes to what changes. A solid line is a step measured in people. A dashed line is a step nobody has measured that way.
Start
Cefepime
What a person takes: Intravenous infusion or intramuscular injection, supplied as cefepime hydrochloride with L-arginine.
The measurement behind this step
Parenteral only; there is no oral form. Eliminated almost entirely by the kidney as unchanged drug, which is why exposure rises steeply when renal function falls and why the drug is removed by haemodialysis. Co-formulated with L-arginine as a buffer.
Getting in
Given into a vein, carrying two opposite charges at once
The molecule has a permanent positive charge at one end and a negative one at the other. That balance is deliberate, and it is what lets the drug slip through the pores of a bacterium’s outer skin faster than its predecessors.
──Measured in people. Written by a person from the study named beside the step. Not signed off as a reviewed claim.
The measurement behind this step
The quaternary N-methylpyrrolidinium group at position 3 gives cefepime a permanent cation and, with the C4 carboxylate, a zwitterionic character. Zwitterions traverse Gram-negative porin channels more rapidly than anionic cephalosporins, which raises the periplasmic concentration achieved for a given plasma concentration.
It reaches the periplasm before the defences can act
Bacteria keep their defence enzymes in the gap between the outer skin and the wall. A drug that crosses quickly is exposed to them for less time, which is part of how cefepime survives where older cephalosporins do not.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
Rapid porin flux reduces the residence time available for periplasmic beta-lactamase hydrolysis. Combined with poor affinity for AmpC enzymes, this is why derepressed AmpC producers such as Enterobacter that defeat ceftazidime often remain susceptible to cefepime.
Its ring is a poor meal for one whole enzyme family
Bacteria have several different families of enzyme that destroy this class of drug. Cefepime is built to be a bad fit for one of the most troublesome families. It remains vulnerable to the others.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
Low affinity for class C AmpC cephalosporinases is the defining resistance advantage. Class A extended-spectrum beta-lactamases including the CTX-M family, and class B and class D carbapenemases, hydrolyse cefepime efficiently, so the advantage is enzyme-specific rather than general.
Inside the periplasm it latches onto the enzymes that stitch the bacterial wall together, chiefly the one that builds the wall across the middle when the cell divides.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
Cefepime acylates PBP3 preferentially and PBP2 substantially in Gram-negative organisms, and retains meaningful activity against Gram-positive penicillin-binding proteins, which is the basis of its unusual dual-spectrum profile compared with ceftazidime.
With cross-linking blocked, the bacterium keeps cutting its own wall to grow and cannot repair it. Internal pressure does the rest.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
Killing is time-dependent, driven by the fraction of the dosing interval during which free drug concentration exceeds the minimum inhibitory concentration, and requires actively dividing organisms.
Cefepime is cleared almost entirely by the kidneys. When the kidneys are not working, it accumulates, reaches the brain, and interferes with the signal that quietens nerve cells — producing confusion, twitching, or seizures that do not look like seizures.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
Elimination is predominantly renal and unchanged. Accumulation produces concentration-dependent GABA-A receptor antagonism and the syndrome described in the label: encephalopathy, aphasia, myoclonus, seizures and non-convulsive status epilepticus, life-threatening or fatal in reported cases, mostly reversible on discontinuation or after haemodialysis. In the randomised ACORN comparison, cefepime recipients had fewer days alive and free of delirium and coma (OR 0.79, 95% CI 0.65 to 0.95).
No suggested links are held for this record, so nothing is hidden from this path.
What we know
The record describes 6 steps from taking it to an effect in a person.
How we know it
Each step names the study behind it in the technical detail beside it.
What this does not prove
A change inside the body is a reason to look. It is not a result in a person.
Why it matters
A reader can see exactly where the chain stops being measured in people.
What we still do not know
No reviewed claim binds any of these steps to a named population.
What is missing or unclear◇Read from sources, not yet reviewed
Were people like you studied?
RNAWiki cannot tell whether a study fits you. It can show who was in it, and where the result stops carrying.
Who was studied
People similar to this profile were included.
Hospitalised adults and children with serious infection, and patients with fever during chemotherapy-induced neutropenia.
Who is missing from the studies
Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
What the label states about particular groups
On pediatric, the label states: “Safety and effectiveness in pediatric patients below the age of 2 months have not been established.”
US prescribing information · d63d360a-15ec-44a4-b80d-b2a5cb5759eb · read 2026-08-30
On older people, the label states: “Of the more than 6400 adults treated with Cefepime for Injection in clinical studies, 35% were 65 years or older while 16% were 75 years or older.”
US prescribing information · d63d360a-15ec-44a4-b80d-b2a5cb5759eb · read 2026-08-30
On people who are pregnant, the label states: “Risk Summary There are no cases of Cefepime for Injection exposure during pregnancy reported from postmarketing experience or from clinical trials.”
US prescribing information · d63d360a-15ec-44a4-b80d-b2a5cb5759eb · read 2026-08-30
On people who are breastfeeding, the label states: “Risk Summary Cefepime is present in human breast milk at low concentrations (approximately 0.5 mcg/mL) following a single intravenous dose of 1000 mg.”
US prescribing information · d63d360a-15ec-44a4-b80d-b2a5cb5759eb · read 2026-08-30
On people with reduced kidney function, the label states: “Adjust the dose of Cefepime for Injection in patients with creatinine clearance less than or equal to 60 mL/min to compensate for the slower rate of renal elimination. [ See Dosage Adjustments in Patients with Renal Impairment (2.3) ]”
US prescribing information · d63d360a-15ec-44a4-b80d-b2a5cb5759eb · read 2026-08-30
Where the result stopped carrying
The 2007 meta-analysis signal was strengthened rather than weakened by restricting to higher-quality trials, and still did not replicate in patient-level data
Neurotoxicity is not confined to unadjusted dosing in renal impairment; the label states some cases occurred with appropriate adjustment
The substitution away from piperacillin-tazobactam achieved no measurable kidney benefit and produced measurable neurological harm
Only eight generic products appear in the United States acquisition-cost survey, a thin base for an empirical agent in neutropenic fever
This is a scope explorer, not a diagnosis engine.
It shows who was studied so you can see whether people similar to you were included.
RNAWiki cannot tell whether a study fits you. It can show who was in it.
What it would be like to take◇Read from sources, not yet reviewed
Why it might seem to do nothing
A real effect and a noticed effect are different things. These are the recorded reasons the two come apart.
It was studied in different people
The people in the studies were not much like the reader.
On this record: Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
The evidence may simply be wrong
Small early studies often do not hold up.
On this record: RNAWiki has not yet published a reviewed conclusion for this use.
Other reasons RNAWiki checked and found nothing for (11)
It was studied for a different goal
The studies measured something else entirely. Nothing in this record points to this reason.
A different form was studied
The studied form is not the form on the shelf. Nothing in this record points to this reason.
There was nothing to correct
Where a level is already normal, topping it up may change nothing. Nothing in this record points to this reason.
Something else had to happen too
In the studies it was paired with training, a diet or another treatment. Nothing in this record points to this reason.
The change is too small to feel
A real change can still sit below what a person notices. Nothing in this record points to this reason.
Day-to-day swing hides it
Sleep, food, stress and time of day move most numbers more than this would. Nothing in this record points to this reason.
Not enough time yet
The studies ran longer than the person has waited. Nothing in this record points to this reason.
It was not taken as studied
Missed days change the result, and studies count them. Nothing in this record points to this reason.
Something else changed at the same time
Two changes at once cannot be told apart afterwards. Nothing in this record points to this reason.
The product may not be what it says
Contents of a sold product are not always what the label states. Nothing in this record points to this reason.
No recorded reason
RNAWiki has nothing stored that would explain it. Nothing in this record points to this reason.
None of these is a reason to take more. Taking more is not a step this page ever suggests.
What it would be like to take◇Read from sources, not yet reviewed
What taking it involves
The recorded facts about getting hold of it and using it. Nothing here is a suggestion about what you should do.
How it is supplied
Given by a clinician
❝ Quoted from a source
Where this came from
Copied from a source RNAWiki stored, with the source named.
Read from the recorded approval status.
No source is stored against this line.
Form and route
Intravenous infusion or intramuscular injection, supplied as cefepime hydrochloride with L-arginine
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The form and route recorded on this substance.
No source is stored against this line.
Who oversees it
RNAWiki has not recorded a supervision or regulatory status for this substance.
❝ Quoted from a source
Where this came from
Copied from a source RNAWiki stored, with the source named.
No register row and no identity class settled the question.
No source is stored against this line.
What is in the pack
Parenteral only; there is no oral form. Eliminated almost entirely by the kidney as unchanged drug, which is why exposure rises steeply when renal function falls and why the drug is removed by haemodialysis. Co-formulated with L-arginine as a buffer.
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
Recorded notes on how this is sold and what that means for what is in the pack.
No source is stored against this line.
Where it is registered
Regulatory records are listed in the technical disclosure at the foot of this page.
# Counted from records
Where this came from
A count of rows RNAWiki holds. It describes our records, not your body.
Register entries are stored per jurisdiction and shown with their dates.
No source is stored against this line.
Why people stop
Not recorded.
∅ Nothing recorded
Where this came from
RNAWiki holds nothing here and says so rather than guessing.
No record of why people stopped taking it is stored for this substance.
No source is stored against this line.
What it would be like to take◇Read from sources, not yet reviewed
What can go wrong
Sorted by where each line came from. A regulator's label and a report somebody sent in are not the same kind of fact.
·Worth asking a clinician aboutWritten into the record from the studies named on this page
The distinctive harm is neurological: the label records life-threatening and fatal encephalopathy, aphasia, myoclonus, seizures and non-convulsive status epilepticus, mostly but not exclusively in renal impairment without appropriate dosage adjustment, and usually reversible on discontinuation or after haemodialysis. The randomised ACORN comparison quantified this as fewer days alive and free of delirium and coma than piperacillin-tazobactam. Cross-hypersensitivity among beta-lactams may occur in up to 10% of patients with a history of penicillin allergy, per the label. Clostridioides difficile-associated diarrhoea is reported as with essentially all antibacterials. The mortality question raised in 2007 was not confirmed by the regulator’s analysis of 88 trials.
Nobody counted how many people took this and were fine, so this cannot be turned into a rate.
Over a long time. No completed tested study window is recorded, so long-term effects are not established by the registry record.
Groups the studies covered thinly. Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
What is missing or unclear◇Read from sources, not yet reviewed
Does the exact form matter?
Evidence belongs to the exact thing that was tested. A different salt, a different mixture or a different preparation is a different question.
The form that was studied
Intravenous infusion or intramuscular injection, supplied as cefepime hydrochloride with L-arginine
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The form used in the studies cited on this page.
No source is stored against this line.
What is sold
Eliminated almost entirely by the kidney as unchanged drug, which is why exposure rises steeply when renal function falls and why the drug is removed by haemodialysis. Co-formulated with L-arginine as a buffer.
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
Recorded notes on which forms are sold and how they compare.
No source is stored against this line.
What is recorded as being sold
37 products list this as an active ingredient in the United States drug directory. 36 of them contain it and nothing else.
FDA National Drug Code directory · 25021-122 · read 2026-08-29
They are sold as injection, powder, for solution, injection, solution and powder, taken intramuscular and intravenous.
FDA National Drug Code directory · 25021-122 · read 2026-08-29
The regulator's established pharmacologic class for it is cephalosporin antibacterial [epc] and cephalosporins [cs].
FDA National Drug Code directory · 25021-122 · read 2026-08-29
15 published labels name it as an active ingredient. 14 of them describe this substance alone, which is where its own label text on this page comes from.
US prescribing information · d63d360a-15ec-44a4-b80d-b2a5cb5759eb · read 2026-08-29
Those labels are classed as human prescription drug.
US prescribing information · d63d360a-15ec-44a4-b80d-b2a5cb5759eb · read 2026-08-29
Cefepime is intramuscular at 3 DOSAGE FORMS AND STRENGTHS Cefepime for Injection, USP is a sterile white to pale yellow powder of cefepime in single-dose vials for reconstitution and it is available in the following strengths: • 0.5 gram per vial •…, recorded as fda label in effect 2023-05-10 in the United States.
US prescribing information · d63d360a-15ec-44a4-b80d-b2a5cb5759eb · read 2026-08-30
Evidence carries across two names for one substance. It does not carry across a salt, a mirror form or a mixture.
What it would be like to take◇Read from sources, not yet reviewed
What you could measure
This one is decided with a clinician, so this section holds questions to ask rather than a plan to run.
RNAWiki could not confidently classify this substance, so no self-experiment plan is offered.
Questions worth asking
Which of the trials of Cefepime studied people like me?
What was measured, and for how long?
Was the result a laboratory value or a health outcome?
What would we watch for, and when would we stop?
Tracking can show whether something changed for you. It cannot show what caused it.
RNAWiki records evidence. It does not say whether this substance is right for you.
What is missing or unclear◇Read from sources, not yet reviewed
Claims that go past the evidence
Things said about this substance that sound reasonable, and the exact step that is missing between the evidence and the claim.
✗Goes past the evidence
That cefepime increases mortality — a published signal of RR 1.26 that did not survive access to patient-level data from 88 trials
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That piperacillin-tazobactam damages kidneys and cefepime spares them, the inference behind a decade of substitution, unconfirmed by randomisation
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That an in vitro susceptible result predicts clinical success against ESBL producers, where cefepime shows a marked inoculum effect
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That a single-centre pragmatic trial in one American academic hospital transfers unchanged to other systems and case mixes
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
What is missing or unclear◇Read from sources, not yet reviewed
What nobody knows yet
Open questions, each with why it is open and what would close it.
Missing populations
Which groups were under-represented in the studies has not been recorded.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Missing long-term data
No completed tested study window is recorded.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
No reviewed conclusion
RNAWiki has not yet published a reviewed conclusion for this use.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Missing interaction studies
No interaction was found in the registers checked. Not finding one is not the same as showing there is none.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Formulation uncertainty
Several salts, forms or products of Cefepime are recorded. Results from one form may not transfer to another.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Mechanism not reviewed
No reviewed mechanism story exists for this substance.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
What happened in people◇Read from sources, not yet reviewed
Check any of this yourself
Every line above traced back to the study it came from. This is the technical layer, and the vocabulary changes here.
Every line above can be traced to the study named beside it. Follow the link and read it.
Accused of increasing mortality in 2007, cleared by the regulator’s data in 2010
In plain words
A pooled analysis of 57 trials reported that more people died on cefepime than on other antibiotics of the same family. It caused a genuine scare. The FDA then went back to the raw data from 88 trials, including unpublished ones, and found no significant difference.
What was measured
That cefepime increases mortality relative to other beta-lactams — a signal that survived quality-based sensitivity analysis in the published literature and did not survive access to the underlying patient-level data
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Yahav and colleagues systematically reviewed randomised trials comparing cefepime with another beta-lactam and found all-cause mortality higher with cefepime across 57 trials (risk ratio 1.26, 95% CI 1.08 to 1.49). Sensitivity analysis by methodological quality made the signal larger, not smaller: RR 1.52 (1.20 to 1.92) in trials reporting adequate allocation-sequence generation and 1.36 (1.09 to 1.70) with adequate concealment. There were no significant differences in treatment failure, superinfection or adverse events. The FDA then accessed published and unpublished trial data directly. The trial-level meta-analysis covered 88 trials, 9,467 cefepime and 8,288 comparator patients: 30-day all-cause mortality was 6.21% against 6.00%, adjusted risk difference 5.38 per 1,000 (95% CI -1.53 to 12.28). The patient-level analysis covered 35 trials, 5,058 and 3,976 patients: 5.63% against 5.68%, adjusted risk difference 4.83 per 1,000 (95% CI -4.72 to 14.38). A sensitivity analysis restricted to the 24 febrile neutropenia trials also showed no significant increase (9.67 per 1,000, 95% CI -2.87 to 22.21).
Written into the record, not signed off as a reviewed claim
No kidney difference against piperacillin-tazobactam in 2,511 randomised patients
In plain words
For years hospitals switched patients from piperacillin-tazobactam to cefepime to protect their kidneys, on the strength of database studies. When it was finally tested by randomisation, there was no kidney difference at all.
What was measured
Highest stage of acute kidney injury or death by day 14 on a five-level ordinal scale
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The ACORN trial randomised 2,511 adults for whom a clinician ordered antipseudomonal antibiotics within 12 hours of presenting to an emergency department or medical intensive care unit at a United States academic centre. The primary outcome, the highest stage of acute kidney injury or death by day 14 on a five-level ordinal scale, did not differ: 85 of 1,214 in the cefepime group (7.0%) reached stage 3 acute kidney injury and 92 (7.6%) died, against 97 of 1,297 (7.5%) and 78 (6.0%) with piperacillin-tazobactam — odds ratio 0.95 (95% CI 0.80 to 1.13), P=.56. Major adverse kidney events at day 14 were 10.2% against 8.8%, absolute difference 1.4% (95% CI -1.0 to 3.8). Median age was 58, 42.7% were female, 94.7% were enrolled in the emergency department, and 77.2% were receiving vancomycin at enrolment.
Written into the record, not signed off as a reviewed claim
The same trial found cefepime caused more delirium and coma
In plain words
The trial was designed to settle a kidney argument. It settled it, and then found the harm nobody was arguing about: patients on cefepime spent fewer days awake and clear-headed.
What was measured
Days alive and free of delirium and coma within 14 days
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
In ACORN, days alive and free of delirium and coma within 14 days were a mean 11.9 (SD 4.6) in the cefepime group against 12.2 (SD 4.3) with piperacillin-tazobactam, odds ratio 0.79 (95% CI 0.65 to 0.95). The published conclusion states it directly: treatment with cefepime resulted in more neurological dysfunction. This is consistent with the label, which records life-threatening and fatal encephalopathy, aphasia, myoclonus, seizures and non-convulsive status epilepticus, and which notes that although most cases occurred in renal impairment without appropriate dosage adjustment, some occurred in patients whose dosage was appropriately adjusted. The mechanism is concentration-dependent GABA-A receptor antagonism.
Written into the record, not signed off as a reviewed claim
A decade of substitution to protect kidneys rested on database associations
In plain words
The reason so many patients were switched to cefepime was a set of observational studies linking piperacillin-tazobactam plus vancomycin to kidney injury. Those studies could not separate the drug from the patients who received it. The randomised answer, when it came, was no difference.
What was measured
That piperacillin-tazobactam causes acute kidney injury and cefepime avoids it — an inference from non-randomised cohorts that a 2,511-patient randomised trial did not confirm, and which came with an unmeasured neurological cost
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The hypothesis that piperacillin-tazobactam causes acute kidney injury, particularly with vancomycin, came from retrospective cohorts and pharmacovigilance analyses in which treatment assignment was decided by clinicians who could see how sick each patient was. ACORN removed that by randomising, and found the primary ordinal outcome unchanged (OR 0.95, 95% CI 0.80 to 1.13) and major adverse kidney events at 14 days statistically indistinguishable. Notably 77.2% of ACORN participants were receiving vancomycin at enrolment, so the trial tested the combination that generated the concern rather than an artificial monotherapy comparison. What the substitution did buy, measurably, was more delirium and coma.
Written into the record, not signed off as a reviewed claim
A susceptible laboratory result overstates what happens in a heavy infection
In plain words
Against bacteria carrying extended-spectrum defence enzymes, cefepime can look effective in the laboratory at the standard bacterial density and much less effective when there are far more bacteria — which is the situation in a real abscess or bloodstream infection.
What was measured
Shift in minimum inhibitory concentration with increasing inoculum against ESBL-producing Enterobacterales
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
Cefepime remains stable to AmpC cephalosporinases, which is the advantage it was designed around, but it is hydrolysed by extended-spectrum beta-lactamases. Against ESBL producers it shows a pronounced inoculum effect: minimum inhibitory concentrations rise substantially when the test inoculum is raised from the standard 5x10^5 CFU/mL toward the densities found in undrained infection, so an isolate reported susceptible on a routine plate may not behave that way clinically. This is why cefepime is not the agent supported by the randomised evidence in ceftriaxone-resistant bloodstream infection, and why that evidence points to a carbapenem instead.
Written into the record, not signed off as a reviewed claim
How many documents were read
14 documents were read for this substance.
RNAWiki source record
14 of them state the same proteinBinding, and they agree.
RNAWiki source record
Where else this substance is registered
FDA substance identifier (UNII)
I8X1O0607P
RxNorm concept
1665088
Checks this page had to pass
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No registered study is classified as testing this substance.
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Canonical metadata present
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What is missing or unclear◇Read from sources, not yet reviewed
How this medicine reached us
Kept near the foot of the page. A historical event moves up only when it changes something about this substance today.
Withdrawn in United States, 2013, for "Presence of Particulate Matter: B. Braun Medical Inc. is recalling several injectable products due to visible particulate matter found in reserve sample units." (openFDA drug enforcement Class I recall)
Withdrawn in United States, 2013, for "Presence of Particulate Matter: The 1g Cefepime for Injection USP and Dextrose Injection USP lot has been found to contain visible organic particulate matter in a reserve sample unit." (openFDA drug enforcement Class I recall)
What the approval register records
14 approved applications cover products containing this substance. The earliest was NDA050679, approved 19960118 to HOSPIRA INC.
This order is fixed in code and does not count clicks or time on the page.
What is not here
7 questions this page could not answer
These sections were prepared and left out because there was nothing to put in them. They are listed rather than hidden, so the gaps in this record are visible.
What was measured, goal by goal — found nothing in the sources checked.
How close this is to real life — found nothing in the sources checked.
Felt, measured, or meaningful — found nothing in the sources checked.
How long anything takes — found nothing in the sources checked.
What it may clash with — found nothing in the sources checked.
Other ways to the same goal — found nothing in the sources checked.
What changed on this page — found nothing in the sources checked.
The record as stored
The full record, for auditing
Everything above is built from what is below. This layer keeps the technical vocabulary, record identifiers and every stored row, so a reader who wants to check the page can.
The older medicine-wide conclusion held in this record
Written for a clinical reader, and about the medicine as a whole rather than about one indication, population and set of trials. RNAWiki does not treat it as a programme conclusion and no reviewer has signed it off in that form. It is here word for word because it is what the record holds.
A fourth-generation cephalosporin whose zwitterionic charge lets it cross the Gram-negative outer membrane quickly and whose ring resists AmpC enzymes — a 2007 meta-analysis of 57 trials reported higher all-cause mortality than other beta-lactams (RR 1.26, 95% CI 1.08 to 1.49), the FDA’s own analysis of 88 trials in 17,755 patients found no significant increase, and the 2,511-patient ACORN trial in 2023 found no kidney difference against piperacillin-tazobactam but fewer days free of delirium and coma (OR 0.79, 95% CI 0.65 to 0.95).
Recorded evidence blocks (8)
Q1
On the Cefepime label: indicated for what?
"Cefepime Injection is a cephalosporin antibacterial indicated in the treatment of the following infections caused by susceptible isolates of the designated microorganisms: pneumonia ( 1.1 ); empiric therapy for febrile neutropenic patients ( 1.2 ); uncomplicated and complicated urinary tract infections ( 1.3 );…": indications and usage on Cefepime's label. DailyMed label · be5f8ca6-7232-423a-a2d5-cccb7abe7921 · 2026-06-25
Q2
34 registered trials of Cefepime — at which phases?
Registered studies posting no result
25 of 34
34 registered studies of Cefepime: 9 phase3, 9 phase4, 7 phase2, 5 na or unstated, 4 phase1, 1 early phase1. CLINICALTRIALS_SNAPSHOT · 2026-09-01
214 with a PubMed record
Show the evidence
phase3
9
phase4
9
phase2
7
na or unstated
5
phase1
4
early phase1
1
5 more recorded rows
completed
18
terminated
7
unknown
6
recruiting
2
active not recruiting
1
recorded 2026-09-01 · last checked 2026-09-04
Q3
7 of Cefepime's trials stopped: accrual/recruitment, funding/business?
"Trial terminated early per business decision"; 7 of 34 registered studies
Show the evidence
Trial
NCT01110408
terminated; "Trial terminated early per business decision"
NCT01110421
terminated; "Trial terminated early per business decision"
NCT02099240
terminated; "Not enough patient enrollment and lack of staffing"
NCT02168816
terminated; "The study was stopped for feasibility (i.e., low recruitment)"
NCT02302092
terminated; "Study was prematurely terminated due to administrative and strategic reasons"
NCT02732327
terminated; "No longer aligned with the revised clinical development plan and commercial strategy"
1 further recorded trialNCT05079620
terminated; "Under-enrollment"
recorded 2026-09-01 · last checked 2026-09-04
Q4
Human studies of Cefepime used Cefepime 2000 mg — over how long?
Human studies of Cefepime used "Cefepime 2000 mg". ClinicalTrials.gov · 2026-09-01
3 recorded entries; human; also "WCK 5107 1000/2000 mg with Cefepime 2000 mg combination", "Cefepime 1000 MG"
Show the evidence
human
NCT02532140
Cefepime 2000 mg
NCT02532140
WCK 5107 1000/2000 mg with Cefepime 2000 mg combination
NCT06048692
Cefepime 1000 MG
recorded 2026-09-01 · last checked 2026-09-04
Q5
Which 14 trials of Cefepime posted no result?
Posted no result
14 of 14 completed trials
Registrations
NCT00358202, NCT00609375, NCT00137787, NCT02123628, NCT01484015 and NCT02532140, and 8 more
Completion dates
oldest 2006-04; newest 2023-06-30
Show the evidence
Trial
NCT00358202
2006-04
NCT00609375
2007-12
NCT00137787
2010-05
NCT02123628
2012-09
NCT01484015
2012-10
NCT02532140
2015-12
8 further recorded trials
NCT02872038
2016-11-30
NCT03332732
2017-12-20
NCT02820987
2018-10-04
NCT04187755
2019-07-31
NCT05106803
2019-10-01
NCT01431326
2019-11
NCT02795949
2020-01
NCT04033029
2023-06-30
Q6
At the median, Cefepime's trials enrolled 70 people — anything larger?
Median enrolment
70
Largest enrolment
5000
Registered trials counted
33
Q7
What do 1350 spontaneous reports say about Cefepime — and not say?
These are reports people sent to a regulator. They do not show the medicine caused the reaction. Nobody counted how many people took the medicine and reported nothing. The same event can be reported more than once, and many reports are incomplete. News coverage, lawsuits and new warnings change how often people report. A count is not a rate and not a risk.
Cefepime appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 1350 reaction mentions were counted: acute kidney injury 386; encephalopathy 190; pyrexia 124; confusional state 110. FAERS via Open Targets · CHEMBL186 · 2026-06-24
Show the evidence
acute kidney injury
386
encephalopathy
190
pyrexia
124
confusional state
110
drug reaction with eosinophilia and systemic symptoms
105
thrombocytopenia
100
4 more recorded rows
neutropenia
89
myoclonus
83
tubulointerstitial nephritis
82
status epilepticus
81
recorded 2026-06-24 · last checked 2026-09-04
Q8
Which 10 reactions does Cefepime's label not list?
acute kidney injury, confusional state and drug reaction with eosinophilia and systemic symptoms and 7 more reported for Cefepime, absent from its label. FAERS via Open Targets · CHEMBL186 · 2026-06-24
2 label terms; 10 reported and unlisted; be5f8ca6-7232-423a-a2d5-cccb7abe7921
Show the evidence
acute kidney injury
count not stated
confusional state
count not stated
drug reaction with eosinophilia and systemic symptoms
count not stated
encephalopathy
count not stated
myoclonus
count not stated
neutropenia
count not stated
4 more recorded rows
pyrexia
count not stated
status epilepticus
count not stated
thrombocytopenia
count not stated
tubulointerstitial nephritis
count not stated
recorded 2026-06-24 · last checked 2026-09-04
Where it is registered
Where it’s registered
Withdrawn in United States, 2013, for "Presence of Particulate Matter: B. Braun Medical Inc. is recalling several injectable products due to visible particulate matter found in reserve sample units." (openFDA drug enforcement Class I recall)
Withdrawn in United States, 2013, for "Presence of Particulate Matter: The 1g Cefepime for Injection USP and Dextrose Injection USP lot has been found to contain visible organic particulate matter in a reserve sample unit." (openFDA drug enforcement Class I recall)
ChEMBL 37 — CC BY-SA 3.0 Unported · ChEMBL ATC CC BY-SA · ClinicalTrials.gov — US Government work · Open Targets 26.06 — CC0 · mixed register set; per-register licences in docs/specs/corpus-20k-sources.md · openFDA / DailyMed — US Government work · openFDA enforcement — US Government work
✗ required summary fields resolved: 4 required field(s) not terminal: Why people use it, Best-supported result, Biggest unanswered question, Human evidence
✓ public claims reviewed: 0 reviewed claim(s); drafts are never rendered
✓ source coverage passed: 7 source rows
✓ no critical contamination: no quarantine open
✓ canonical metadata passed: slug and display name present
✓ no raw internal fields: enforced by the copy-contract test over the rendered page
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