This page shows what was measured, who it was measured in, and what that does not settle.
What Piperacillin and Tazobactam does in the body
Severe hospital infections of the abdomen, skin, lungs and pelvis, given by drip
Piperacillin is a wide-reaching penicillin that jams the tool bacteria use to build their cell wall. Many bacteria destroy penicillins with an enzyme, so the bag also contains tazobactam, a decoy that the enzyme attacks and is destroyed by. Between them they cover almost everything a hospital infection is likely to be, which is exactly why the drug is started before anyone knows what the infection is.
What happened in people
No difference in highest stage of acute kidney injury or death against cefepime in 2,511 randomised patients (OR 0.95, 95% CI 0.80 to 1.13)
✎ 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 recorded finding that sits closest to something a person would notice. Written into the record, not signed off, and it carries no population or interval.
That this combination causes acute kidney injury, particularly with vancomycin — the belief that reshaped a decade of prescribing, unconfirmed by randomisation
Where it acts
The bacterial periplasm — where tazobactam intercepts the enzyme and piperacillin reaches the wall-building machinery
Kind of result
Living longer, or avoiding a major event
Supervision
RNAWiki has not recorded a supervision or regulatory status for this substance.
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.
A limit recorded against this substance. Not signed off as a reviewed claim.
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.
All-cause mortality 30 days after randomisation
✗ The study did not show it
Who was studied
MERINO (NCT02176122)
How many people
379
Study design
Phase 4, randomised, parallel-group, non-inferiority, 26 sites in 9 countries
Compared against
Not recorded for this study
Kind of result
Living longer, or avoiding a major event
What was found
12.3% (23 of 187) against meropenem 3.7% (7 of 191); risk difference 8.6%, one-sided 97.5% CI upper bound 14.5% against a 5% margin, P=.90 for non-inferiority
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. Central retesting later showed local susceptibility results for piperacillin-tazobactam were unreliable; excluding isolates with MIC above 16 mg/L reduced the absolute risk increase from 9% to 5% with an interval crossing zero. The trial is a drug result and a diagnostic result at the same time, and it is usually quoted only as the first.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Intravenous infusion, supplied as a lyophilised fixed-ratio powder with edetate disodium and sodium citrate
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
Odds ratio 0.95 (95% CI 0.80 to 1.13), P=.56 — no excess kidney injury against cefepime; major adverse kidney events 8.8% against 10.2%, absolute difference 1.4% (95% CI -1.0 to 3.8)
Repeated elsewhere
Unreplicated
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. Single centre, 94.7% enrolled in the emergency department, unblinded. Days alive and free of delirium and coma favoured this arm, which was a secondary outcome and is the finding that changed practice more than the primary one did.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Intravenous infusion, supplied as a lyophilised fixed-ratio powder with edetate disodium and sodium citrate
Interval reported. 95% CI 0
Written into the record, not signed off as a reviewed claim.
All-cause mortality within 90 days of randomisation
✗ The study did not show it
Who was studied
BLING III (NCT03213990)
How many people
7031
Study design
Phase 4, international, open-label, randomised, 104 intensive care units
Compared against
Not recorded for this study
Kind of result
Living longer, or avoiding a major event
What was found
Continuous 24.9% (864 of 3,474) against intermittent 26.8% (939 of 3,507); absolute difference -1.9% (95% CI -4.9 to 1.1), odds ratio 0.91 (95% CI 0.81 to 1.01), P=.08
Repeated elsewhere
Partially Replicated
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. Clinical cure was higher with continuous infusion, 55.7% against 50.0% (absolute difference 5.7%, 95% CI 2.4 to 9.1), while the mortality primary endpoint missed. The authors state the confidence interval includes both no important effect and a clinically important benefit — an unusually honest way to describe P=.08.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Intravenous infusion, supplied as a lyophilised fixed-ratio powder with edetate disodium and sodium citrate
Interval reported. 95% CI -4
Written into the record, not signed off as a reviewed claim.
RNAWiki holds 3 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
Piperacillin and Tazobactam
What a person takes: Intravenous infusion, supplied as a lyophilised fixed-ratio powder with edetate disodium and sodium citrate.
The measurement behind this step
Parenteral only. The current formulation contains edetate disodium and sodium citrate, which made it compatible with lactated Ringer’s solution where the earlier formulation was not. Predominantly renally cleared, with a minor biliary route for piperacillin. It is the agent most often combined with vancomycin in empirical intensive care regimens, which is why the kidney question mattered so much.
Getting in
Two molecules in a fixed ratio, given by drip
One of the pair kills bacteria across an unusually wide range. The other kills almost nothing and exists only to absorb the enzyme that would otherwise destroy the first. They are freeze-dried together in a fixed proportion.
╌╌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
Piperacillin is a ureidopenicillin; tazobactam is a penicillanic acid sulfone with negligible intrinsic antibacterial activity. The combination is supplied lyophilised at a fixed 8:1 ratio with edetate disodium and sodium citrate, a formulation that made the product compatible with lactated Ringer’s solution.
Both cross into the periplasm, and one of them can be pumped back out
The drugs have to reach the space between a bacterium’s outer skin and its wall. Pseudomonas has pumps that push the killing molecule straight back out again, which is one of the ways it becomes resistant without changing its target at all.
╌╌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
Entry is through outer-membrane porins. In Pseudomonas aeruginosa, piperacillin is a substrate of the MexAB-OprM efflux system, so periplasmic concentration is set by the balance of influx and export. Efflux upregulation confers resistance with no change in penicillin-binding proteins and no beta-lactamase.
Resistant bacteria fill the periplasm with enzymes that cut penicillins apart. Tazobactam is shaped enough like a penicillin that the enzyme attacks it, and the reaction leaves the enzyme permanently broken.
╌╌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
Tazobactam is a mechanism-based inactivator of class A serine beta-lactamases including TEM and SHV enzymes. It has limited activity against class C AmpC cephalosporinases, none against class B metallo-beta-lactamases, and it is overwhelmed when an isolate carries an extended-spectrum enzyme alongside OXA-1 — the combination the MERINO reanalysis identified as carrying the highest excess mortality.
With the defence enzymes used up, piperacillin reaches the tools that stitch the bacterial wall together and locks onto them.
╌╌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
Piperacillin acylates bacterial DD-transpeptidases across an unusually wide range: Gram-positive cocci, Enterobacterales, anaerobes including Bacteroides fragilis, and Pseudomonas aeruginosa. Anaerobic cover in a single agent is the property that makes this the default in intra-abdominal infection.
Wall repair stops, wall demolition continues, and the bacterium bursts under its own pressure.
╌╌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 on the fraction of the dosing interval with free concentration above the minimum inhibitory concentration — the argument for prolonged infusion, supported at high certainty by pooled analysis of 18 trials and not reached by the largest single trial in that pool.
Where the reputation and the evidence part company
For years this drug was blamed for kidney damage on the basis of records rather than trials. When it was finally randomised against its main rival, kidneys came out the same and brains came out better.
──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
In 2,511 randomised patients, 77.2% of whom were also receiving vancomycin, the highest stage of acute kidney injury or death by day 14 was unchanged (OR 0.95, 95% CI 0.80 to 1.13) and major adverse kidney events at day 14 were 8.8% against cefepime’s 10.2%. Days alive and free of delirium and coma favoured piperacillin-tazobactam. Piperacillin also interferes with tubular creatinine secretion and with some creatinine assays, which can raise a measured creatinine without a fall in filtration.
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 severe infection, particularly intra-abdominal infection, hospital-acquired pneumonia and neutropenic fever.
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.
Where the result stopped carrying
It failed its own carbapenem-sparing trial, with a mortality difference of 8.6 percentage points against a 5% non-inferiority margin
Routine susceptibility testing for it proved unreliable enough to distort a multinational randomised trial
Isolates co-carrying an extended-spectrum beta-lactamase and OXA-1 had the highest excess mortality of any subgroup, 14% (95% CI 2 to 28%)
The mortality endpoint of the largest infusion trial ever conducted in this class returned P=.08 and did not meet significance
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, supplied as a lyophilised fixed-ratio powder with edetate disodium and sodium citrate
✎ 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. The current formulation contains edetate disodium and sodium citrate, which made it compatible with lactated Ringer’s solution where the earlier formulation was not. Predominantly renally cleared, with a minor biliary route for piperacillin. It is the agent most often combined with vancomycin in empirical intensive care regimens, which is why the kidney question mattered so much.
✎ 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 reputation for nephrotoxicity, particularly alongside vancomycin, was not confirmed when 2,511 patients were randomised, three-quarters of them on vancomycin. Part of the historical signal is likely analytical: piperacillin interferes with tubular creatinine secretion and with some creatinine assays. Real and documented harms include hypersensitivity as with any penicillin, Clostridioides difficile-associated diarrhoea, thrombocytopenia and other cytopenias with prolonged use, and hypokalaemia from the sodium load. Neurological toxicity is less than with cefepime in the randomised comparison. It is not reliable against extended-spectrum beta-lactamase producers and should not be inferred to be from a routine susceptibility report.
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, supplied as a lyophilised fixed-ratio powder with edetate disodium and sodium citrate
✎ 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
The current formulation contains edetate disodium and sodium citrate, which made it compatible with lactated Ringer’s solution where the earlier formulation was not. Predominantly renally cleared, with a minor biliary route for piperacillin. It is the agent most often combined with vancomycin in empirical intensive care regimens, which is why the kidney question mattered so much.
✎ 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
32 published labels name it as an active ingredient. None of them describes this substance alone, so no label text on this page can be attributed to it rather than to a combination.
US prescribing information · 68d5384d-1691-4afc-8a1a-488f8e2ef2c5 · read 2026-08-29
Those labels are classed as human prescription drug.
US prescribing information · 68d5384d-1691-4afc-8a1a-488f8e2ef2c5 · read 2026-08-29
107102 marketed supplement labels list this ingredient, classed as botanical with nutrients, multi-vitamin and mineral (mvm) and non-nutrient/non-botanical.
Those labels carry all other, nutrient and structure/function claims. A claim of that kind is written by the manufacturer and is not assessed by any regulator, so its presence says nothing about whether it is true.
Piperacillin and Tazobactam is intravenous at 3 DOSAGE FORMS AND STRENGTHS Piperacillin and tazobactam for injection is supplied as a white to off-white powder in bottles of the following sizes: Each Piperacillin and Tazobactam for Injection 40.5 g pharmacy bulk bo…, recorded as fda label in effect 2024-10-16 in the United States.
US prescribing information · e53ebafc-3afa-4a1e-9313-fecd1c1c5d7c · 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 Piperacillin and Tazobactam 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 this combination causes acute kidney injury, particularly with vancomycin — the belief that reshaped a decade of prescribing, 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 prolonged infusion reduces mortality, which pooled Bayesian analysis supports at high certainty and the largest single trial did not reach
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 susceptibility reported by a routine laboratory means the drug will work — central retesting found 6% of MERINO isolates non-susceptible, concentrated in the deaths
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 1993 combination approval implies contemporary evidence for every listed indication; most of them were approved on cure rates without mortality comparison
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 Piperacillin and Tazobactam 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.
MERINO: 12.3% mortality against meropenem’s 3.7%, and non-inferiority not met
In plain words
A nine-country trial tested whether this cheaper, more familiar drug could replace a carbapenem in serious bloodstream infections caused by resistant bacteria. Three times as many patients died on it. The trial’s own conclusion is that its findings do not support using it in that setting.
What was measured
All-cause mortality 30 days after randomisation in a non-inferiority design with a 5% margin
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
MERINO screened 1,646 patients at 26 sites in 9 countries and randomised 391 adults with at least one blood culture growing Escherichia coli or Klebsiella non-susceptible to ceftriaxone but susceptible to piperacillin-tazobactam. Among 379 in the primary analysis population, 30-day all-cause mortality was 23 of 187 (12.3%) with piperacillin-tazobactam against 7 of 191 (3.7%) with meropenem — a risk difference of 8.6% with a one-sided 97.5% confidence bound of 14.5%, against a pre-specified non-inferiority margin of 5%. P for non-inferiority was .90. The result was consistent in the per-protocol population. Non-fatal serious adverse events were 5 of 188 (2.7%) and 3 of 191 (1.6%).
Written into the record, not signed off as a reviewed claim
Much of that failure was the laboratory, not the drug — and the advice stood
In plain words
When every blood isolate was retested centrally, some had been wrongly reported as susceptible. Excluding those cut the mortality gap almost in half and its confidence interval crossed zero. The recommendation did not change, because a drug you cannot reliably test for is a drug you cannot reliably use.
What was measured
That MERINO measured the drug — a large part of what it measured was a diagnostic failure, which changes the explanation without changing the recommendation
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Central broth microdilution and whole genome sequencing covered 320 of 379 isolates. Piperacillin-tazobactam susceptibility was 94% against meropenem’s 100%. A piperacillin-tazobactam MIC above 16 mg/L was the strongest predictor of 30-day mortality after adjustment for confounders (odds ratio 14.9, 95% CI 2.8 to 87.2). The absolute risk increase for piperacillin-tazobactam was 9% (95% CI 3 to 15%) in the original primary analysis population and 8% (95% CI 2 to 15%) in the microbiologically assessable population, falling to 5% (95% CI -1 to 10%) once strains above that MIC were excluded. Isolates co-harbouring an extended-spectrum beta-lactamase and OXA-1 had elevated MICs and the highest risk increase of any subgroup, 14% (95% CI 2 to 28%). The authors concluded that poor reliability of piperacillin-tazobactam susceptibility testing, together with the high prevalence of OXA-1 alongside ESBLs, means meropenem remains preferred.
Written into the record, not signed off as a reviewed claim
It does not damage kidneys more than cefepime, in 2,511 randomised patients
In plain words
For a decade hospitals moved patients off this drug to protect their kidneys. Randomised, against the drug they moved them to, there was no difference at all.
What was measured
Highest stage of acute kidney injury or death by day 14, and days alive and free of delirium and coma
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
ACORN randomised 2,511 adults for whom antipseudomonal antibiotics were ordered within 12 hours of presenting to an emergency department or medical intensive care unit. On the five-level ordinal primary outcome of highest stage of acute kidney injury or death by day 14, 97 of 1,297 in the piperacillin-tazobactam group (7.5%) reached stage 3 acute kidney injury and 78 (6.0%) died, against 85 of 1,214 (7.0%) and 92 (7.6%) with cefepime — odds ratio 0.95 (95% CI 0.80 to 1.13), P=.56. Major adverse kidney events at day 14 were 114 (8.8%) against 124 (10.2%), absolute difference 1.4% (95% CI -1.0 to 3.8). Crucially, 77.2% of participants were receiving vancomycin at enrolment, so the trial tested the combination that generated the original concern. Days alive and free of delirium and coma favoured piperacillin-tazobactam: mean 12.2 (SD 4.3) against 11.9 (SD 4.6), odds ratio 0.79 (95% CI 0.65 to 0.95) against cefepime.
Written into the record, not signed off as a reviewed claim
The nephrotoxicity reputation came from studies that could not control for sickness
In plain words
The claim that this drug plus vancomycin wrecks kidneys came from looking back at records. In those records, the sickest patients got the combination — and the sickest patients get kidney injury. Randomisation removed the confusion and the effect vanished.
What was measured
That piperacillin-tazobactam, especially with vancomycin, causes acute kidney injury — a strongly held inference from non-randomised data that the randomised comparison did not support
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The hypothesis arose from retrospective cohorts and pharmacovigilance disproportionality analyses in which treatment was assigned by clinicians who could see how ill each patient was, a form of confounding by indication that no statistical adjustment fully removes. It changed prescribing at scale. ACORN tested it directly by randomisation, in a population where three-quarters were on vancomycin, and found the primary ordinal outcome unchanged (OR 0.95, 95% CI 0.80 to 1.13) and major adverse kidney events statistically indistinguishable. A second mechanism worth noting is measurement rather than injury: piperacillin-tazobactam interferes with creatinine secretion and some assay methods, so part of the historical signal may be a creatinine rise without a fall in glomerular filtration.
Written into the record, not signed off as a reviewed claim
Prolonged infusion: the biggest trial missed, the pooled analysis says it works
In plain words
Giving this class of antibiotic slowly rather than in short bursts should work better, because they kill in proportion to how long the level stays high. The largest trial ever run on the question, in seven thousand patients, missed statistical significance on survival. A pooled analysis published in the same journal weeks later concluded, with high certainty, that it does save lives.
What was measured
That prolonged infusion reduces mortality — supported at high certainty by a Bayesian pooling of 18 trials, and not established by the single largest trial in that pool, which returned P=.08 on its primary endpoint
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
BLING III randomised 7,031 critically ill adults with sepsis across 104 intensive care units in seven countries to an equivalent 24-hour dose of piperacillin-tazobactam or meropenem by continuous or intermittent infusion. Ninety-day all-cause mortality was 864 of 3,474 (24.9%) against 939 of 3,507 (26.8%) — absolute difference -1.9% (95% CI -4.9 to 1.1), odds ratio 0.91 (95% CI 0.81 to 1.01), P=.08. Clinical cure was higher with continuous infusion, 55.7% against 50.0%, absolute difference 5.7% (95% CI 2.4 to 9.1). Other secondary outcomes did not differ. A Bayesian systematic review of 18 randomised trials in 9,108 critically ill adults, with 17 trials contributing to the primary outcome, then estimated a risk ratio for 90-day mortality of 0.86 (95% credible interval 0.72 to 0.98, I2 21.5%, high certainty), with a 99.1% posterior probability of benefit, alongside intensive care unit mortality 0.84 (0.70 to 0.97) and clinical cure 1.16 (1.07 to 1.31). The earlier MERCY trial of continuous meropenem alone, in 607 patients, had found nothing on its composite endpoint (RR 0.96, 95% CI 0.81 to 1.13).
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What is not here
8 questions this page could not answer
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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.
How this medicine reached us — 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
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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.
An antipseudomonal penicillin paired with a beta-lactamase inhibitor that covers Gram-negatives, Gram-positives and anaerobes in one bag — the ACORN trial in 2,511 patients found it caused no more acute kidney injury or death than cefepime (OR 0.95, 95% CI 0.80 to 1.13) and less neurological dysfunction, and the MERINO trial found 30-day mortality of 12.3% against meropenem’s 3.7% in ceftriaxone-resistant bloodstream infection, missing its non-inferiority margin decisively.
Recorded evidence blocks (6)
Q1
83 registered trials of Piperacillin and Tazobactam — at which phases?
Registered studies posting no result
67 of 83
83 registered studies of Piperacillin and Tazobactam: 25 phase4, 18 phase3, 13 na or unstated, 12 phase2, 10 na, 5 phase1, 1 early phase1. CLINICALTRIALS_SNAPSHOT · 2026-09-01
23 with a PubMed record
Show the evidence
phase4
25
phase3
18
na or unstated
13
phase2
12
na
10
phase1
5
9 more recorded rows
early phase1
1
completed
40
terminated
13
recruiting
10
unknown
10
withdrawn
5
not yet recruiting
3
active not recruiting
1
suspended
1
recorded 2026-09-01 · last checked 2026-09-04
Q2
19 of Piperacillin and Tazobactam's trials stopped: safety, accrual/recruitment, funding/business, sponsor decision unspecified, other?
safety (1), accrual/recruitment (8), funding/business (1), sponsor decision unspecified (2) and other (7): Piperacillin and Tazobactam's stop wording, clustered. CLINICALTRIALS_SNAPSHOT · 2026-09-01
"difficulties by enrolling patients fundings consumed, no staff could be recruited and payed to continue enrolling patients,"; 19 of 83 registered studies
Show the evidence
Trial
NCT00435305
terminated; "difficulties by enrolling patients fundings consumed, no staff could be recruited and payed to continue enrolling patients,"
NCT00816790
terminated; "Study stopped because of study personel movement to another institution."
NCT01694069
terminated; "Recruitment was not sufficient to complete the study"
NCT01853982
terminated; "Terminated to focus on a larger study within the clinical development program."
NCT02099240
terminated; "Not enough patient enrollment and lack of staffing"
NCT02168816
terminated; "The study was stopped for feasibility (i.e., low recruitment)"
13 further recorded trials
NCT02176122
terminated; "Secondary to third interim analysis by the study DSMB."
NCT02732327
terminated; "No longer aligned with the revised clinical development plan and commercial strategy"
NCT03006679
withdrawn; "Sponsor Decision"
NCT03036826
withdrawn; "due to organisational changes"
NCT03108690
withdrawn; "Logistics"
NCT03262142
terminated; "Slow recruitment"
NCT03560232
terminated; "Unable to recruit patients in a timely fashion and unable to recruit sufficient patients"
NCT03862079
withdrawn; "Per PI's request"
NCT03922451
terminated; "COVID-19 - study and recruitment not feasible"
NCT04042077
terminated; "COVID-19 seriously affected the study execution as required by the protocol"
NCT04394182
suspended; "lack of recruitment"
NCT05355350
withdrawn; "No eligible patients"
NCT05753735
terminated; "Principal investigator left the institution."
recorded 2026-09-01 · last checked 2026-09-04
Q3
Human studies of Piperacillin and Tazobactam used Antibiotic treatment (Piperacillin/Tazobactam, 4 gram x 3), followed by 8-10 days of out-hospital oral antibiotic treatment (Ciprofloxacin 500 mgx2,Flagyl 400 mgx3). — over how long?
Human studies of Piperacillin and Tazobactam used "Antibiotic treatment (Piperacillin/Tazobactam, 4 gram x 3), followed by 8-10 days of out-hospital oral antibiotic treatment (Ciprofloxacin 500 mgx2,Flagyl 400 mgx3)." ClinicalTrials.gov · 2026-09-01
2 recorded entries; human; oral; also "Piperacillin-Tazobactam 4 g-0.5 g"
Show the evidence
human
NCT03985514
oral; Antibiotic treatment (Piperacillin/Tazobactam, 4 gram x 3), followed by 8-10 days of out-hospital oral antibiotic treatment (Ciprofloxacin 500 mgx2,Flagyl 400 mgx3).
NCT04233996
Piperacillin-Tazobactam 4 g-0.5 g
recorded 2026-09-01 · last checked 2026-09-04
Q4
Which running trial of Piperacillin and Tazobactam could settle lifespan?
NCT06977347 measures All-cause 28-day mortality, reading out 2027-02-01.
5 open trials; n 100; "Appropriateness of Antibiotic Combination Therapy for Severe Community-acquired Pneumonia in South Korea"
Show the evidence
Trial
NCT06977347
"Appropriateness of Antibiotic Combination Therapy for Severe Community-acquired Pneumonia in South Korea"; n 100; "All-cause 28-day mortality"; 2027-02-01
NCT03671967
"PipEracillin Tazobactam Versus mERoPENem for Treatment of Bloodstream Infections Caused by Cephalosporin-resistant Enterobacteriaceae (PETERPEN)"; n 1084; "All-cause mortality"; 2027-04-01
NCT02735707
"Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community- Acquired Pneumonia"; n 20000; "All-cause mortality"; 2028-02
NCT06184659
"Empirical Meropenem Versus Piperacillin/Tazobactam for Adult Patients With Sepsis"; n 5800; "All-cause mortality"; 2029-03-30
NCT06712641
"Aminoglycosides in Early Sepsis"; n 1900; "30-day mortality"; 2033-05
Q5
Which 27 trials of Piperacillin and Tazobactam posted no result?
Posted no result
27 of 27 completed trials
Registrations
NCT00044746, NCT00044759, NCT00044928, NCT00195533, NCT00438269 and NCT00195286, and 21 more
Completion dates
oldest 2003-01; newest 2024-06-30
Show the evidence
Trial
NCT00044746
2003-01
NCT00044759
2003-01
NCT00044928
2004-02
NCT00195533
2005-03
NCT00438269
2005-03
NCT00195286
2007-07
14 further recorded trials
NCT00253955
2007-11
NCT00491426
2010-11
NCT00703144
2012-08
NCT01697059
2015-05
NCT02730624
2017-01
NCT03376529
2017-12-20
NCT02619149
2018-01
NCT03441529
2018-05-03
NCT02820987
2018-10-04
NCT02473263
2019-02-09
NCT03738683
2019-10-01
NCT01431326
2019-11
NCT02795949
2020-01
NCT03687255
2020-02-15
Q6
At the median, Piperacillin and Tazobactam's trials enrolled 114.5 people — anything larger?
Median enrolment
114.5
Largest enrolment
20000
Registered trials counted
82
Where it is registeredIdentifiers, relations and other names
✗ 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: 4 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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