Why Resistant Urinary Infections Are Hard to Treat

A Common Infection With Growing Resistance

Urinary tract infections are among the most common bacterial infections. Most are simple to treat. Complicated UTIs, which involve the upper urinary tract (pyelonephritis), anatomical or functional problems, catheters, or recent procedures, are harder. When the bacteria are resistant to several drug classes, clinicians can run short of oral options. Some patients then need IV therapy, often in a hospital.

Why Gram-Negative Resistance Matters

Many resistant urinary pathogens are gram-negative bacteria in the Enterobacterales group, including E. coli and Klebsiella pneumoniae. These organisms can produce extended-spectrum beta-lactamases (ESBLs) or carbapenemases, enzymes that inactivate many common antibiotics. Carbapenems have long been the fallback, but overusing them drives further resistance, so clinicians need additional options.

The Aminoglycoside Problem

Aminoglycosides such as gentamicin and amikacin have been used for decades. They kill bacteria effectively, but resistance enzymes called aminoglycoside-modifying enzymes often neutralize them. Their use also carries well-known risks to the kidneys and inner ear, which led many clinicians to avoid them except when necessary.

Key Takeaways

• Zemdri (plazomicin) was approved by the FDA on June 25, 2018, for adults with complicated urinary tract infections, including pyelonephritis, caused by certain Enterobacterales.
• It is an intravenous, once-daily aminoglycoside designed to remain active against many bacteria that resist older aminoglycosides.
• The FDA did not approve Zemdri for bloodstream infections.
• The EPIC trial, the first randomized controlled study of a once-daily aminoglycoside for cUTI, found plazomicin noninferior to meropenem.
• The boxed warning covers nephrotoxicity, ototoxicity, neuromuscular blockade, and fetal harm.
• Therapeutic drug monitoring is recommended for patients with creatinine clearance below 90 mL/min.
• Zemdri is reserved for patients with limited or no alternative treatment options and should be used with susceptibility testing and specialist input.

What Is Zemdri

Brand and Generic Names

Zemdri is the brand name for plazomicin injection. It was developed by Achaogen, Inc., which launched the product in the United States after approval. Plazomicin is a next-generation aminoglycoside, a chemical modification of the older sisomicin structure designed to resist inactivation by common resistance enzymes.

Drug Class

Aminoglycosides are bactericidal antibiotics that bind to the bacterial ribosome and disrupt protein synthesis. Their killing activity depends on concentration, which is why once-daily dosing can be effective. Plazomicin shares this mechanism with the older drugs but differs in its chemical structure.

Dosage Form

Zemdri is supplied as a solution for IV infusion. It is not available as a pill, and it is given under medical supervision.

FDA Approval: June 2018

The Approval Decision

The FDA approved Zemdri on June 25, 2018, according to its approval history. The company announced the approval in a press release issued June 26, 2018. The FDA's approval covered adults with complicated urinary tract infections, including pyelonephritis, caused by certain Enterobacterales who have limited or no alternative treatment options.

Advisory Committee Support

Before approval, an FDA advisory committee voted unanimously in May 2018 in favor of plazomicin for cUTI. The committee's support helped move the application forward, although the FDA still weighed the boxed warnings and the limits of the trial data.

Limits of the Approval

The FDA did not approve plazomicin for bloodstream infections. Its use is restricted to cUTI, and the label emphasizes that the drug should be reserved for situations where other options are limited or unavailable.

How Plazomicin Works

Ribosome Targeting

Plazomicin binds to the 30S subunit of the bacterial ribosome. This binding causes errors in protein synthesis and disrupts the bacterial cell membrane. The combined effect kills susceptible bacteria.

Concentration-Dependent Killing

Aminoglycosides kill bacteria more effectively at higher peak concentrations. This is the reason for once-daily dosing: a large dose produces high peak levels, and the drug's effect persists after levels fall. Once-daily dosing also reduces the time the drug spends at higher levels in the kidneys and ear, though it does not remove the risk.

Why Once-Daily Dosing Was a Focus

Traditional aminoglycosides often require multiple daily doses or careful timing. Once-daily plazomicin is a practical advantage in hospital care, but it still requires monitoring, because drug levels can accumulate in some patients.

Why Plazomicin Was Designed Differently

Resistance to Modifying Enzymes

Many gram-negative bacteria inactivate aminoglycosides by adding chemical groups to them. Plazomicin's structure was designed to resist many of these modifying enzymes. Laboratory studies have shown that it retains activity against many organisms resistant to older aminoglycosides.

Activity Against Beta-Lactamase Producers

Plazomicin shows activity against many ESBL-producing and carbapenemase-producing Enterobacterales. This is why clinicians may consider it when other drug classes are limited. Laboratory activity does not guarantee clinical success, so susceptibility testing matters.

A Narrow Role

Plazomicin is not designed to replace first-line UTI treatment. Its role is in resistant infections where other choices are poor or unavailable.

Approved Use and Limits

Who Is Eligible

The approved population is adults with cUTI, including pyelonephritis, caused by susceptible Enterobacterales. The label emphasizes patients who have limited or no alternative treatment options.

What It Is Not Approved For

Plazomicin is not approved for bloodstream infections, uncomplicated cystitis, or infections in children. Off-label use would be a decision for the treating clinician and infectious disease team, weighing risks carefully.

Susceptibility Testing

Activity depends on the specific organism. Laboratory susceptibility testing should guide use, and results should not be assumed based on the drug class.

The EPIC Trial

Study Design

The EPIC trial, which stands for Evaluating Plazomicin in cUTI, was a randomized, double-blind, multinational noninferiority study. Adults with cUTI were randomly assigned to receive plazomicin or meropenem. The sponsor described EPIC as the first randomized controlled trial of a once-daily aminoglycoside for cUTI, including pyelonephritis.

Dosing in the Trial

In the EPIC trial, plazomicin was given at 15 mg/kg intravenously once daily. The meropenem comparator was given according to standard practice. Dosing in clinical care should follow the current prescribing information and be individualized by the care team.

Why a Noninferiority Design

A noninferiority trial asks whether a new drug is about as effective as the established comparator within a set margin. It does not prove the new drug is better. The EPIC design fits a drug intended for resistant infections, where the question is whether plazomicin is a reasonable option compared with a known standard.

Trial Results Explained

Efficacy Findings

The FDA reviewers concluded that plazomicin was noninferior to meropenem for cUTI, including acute pyelonephritis. Microbiological eradication rates were similar between groups, with eradication above 85 percent in the plazomicin arm according to a published summary of the trial. Differences were not statistically significant in the summary reviewed.

Safety Findings

Renal function-related adverse reactions were reported in 3.6 percent of patients receiving plazomicin compared with 1.3 percent receiving meropenem in one of the trials. The boxed warning reflects the drug's kidney and ear toxicity in the broader safety data.

The Trough Level Signal

Analyses across the trials found that nephrotoxicity was more common in patients whose trough levels were 3 mcg/mL or higher. This relationship is why drug-level monitoring is recommended. Keeping levels in a safer range is a central part of safe use.

Reading the Numbers Carefully

Trial populations are selected, and results may not match every real-world patient. The evidence base is limited to a small number of pivotal studies. Clinicians weigh efficacy, safety, and the availability of alternatives before choosing this drug.

Which Bacteria It Targets

Labeled Organisms

The label covers cUTI caused by susceptible Enterobacterales, including organisms such as E. coli, Klebsiella pneumoniae, Enterobacter cloacae, and Proteus mirabilis. Susceptibility to plazomicin depends on laboratory testing for each isolate.

Resistant Organisms

Laboratory studies have reported activity against many ESBL-producing and carbapenemase-producing Enterobacterales. Some studies of metallo-beta-lactamase producers found that a majority of isolates were susceptible at the FDA breakpoint, though proportions varied across collections. Testing is essential because the answer differs by organism and resistance mechanism.

Why Testing Matters

Some resistance mechanisms affect aminoglycosides, including certain methylase enzymes. Laboratory results, not assumptions about the drug class, should determine whether plazomicin is used.

Limits of Activity

Metallo-Beta-Lactamase Producers

Some clinical summaries note that plazomicin may not be effective against NDM-containing isolates, because these organisms often carry aminoglycoside resistance genes as well. Clinicians should not assume activity against these organisms without testing.

Gram-Positive and Other Organisms

Plazomicin is not a treatment for gram-positive infections such as enterococcal or staphylococcal infections. Its spectrum is centered on gram-negative Enterobacterales.

Intrinsic and Acquired Resistance

Some organisms are intrinsically resistant to aminoglycosides, and others acquire resistance over time. Resistance can emerge during therapy, which is another reason for prompt culture and follow-up testing.

Administration and Dosing Approach

IV Infusion

Zemdri is given as an intravenous infusion. Nurses and pharmacists prepare and administer it, and patients should report any discomfort at the infusion site or other reactions during the infusion.

Once-Daily Schedule

The labeled schedule is once daily. Exact dose and infusion instructions depend on kidney function and the clinical situation. Always confirm current dosing with the prescribing information and your care team, because labeling can change.

Duration of Therapy

Treatment length depends on the infection, response, and culture results. The care team sets the plan and reviews it as the infection responds.

Missed Doses

In a hospital, nursing and pharmacy staff manage missed or delayed doses. Patients should not make up doses on their own.

Monitoring Drug Levels and Kidney Function

Why Monitoring Is Essential

Plazomicin is cleared by the kidneys. When kidney function is reduced, the drug can accumulate and reach potentially toxic levels. The label recommends therapeutic drug monitoring for patients with creatinine clearance below 90 mL/min to avoid these levels.

Baseline and Ongoing Tests

Before starting treatment, clinicians typically check kidney function and may check hearing. During therapy they monitor creatinine, urine output, and drug levels, and they adjust treatment as needed. Patients with existing kidney disease need closer attention.

Trough Levels

Trough levels, measured just before the next dose, help show how much drug remains in the body. Higher trough values have been linked to more kidney injury, so the care team may adjust dosing based on results.

Coordinating Care

Monitoring works best when the infectious disease pharmacist, nephrology team, and nursing staff communicate about lab results and symptoms.

Kidney Injury Warning

What the Warning Means

Nephrotoxicity, or kidney injury, is the first item in the boxed warning. It can present as reduced urine output, rising creatinine, swelling, or fatigue, though some people have no symptoms early on. Blood and urine tests detect it most reliably.

Who Is at Higher Risk

Risk is greater in people with impaired kidney function, older adults, and those taking other nephrotoxic drugs such as certain antibiotics, diuretics, or NSAIDs. Dehydration and sepsis can also increase risk.

What to Report

Tell your care team right away about decreased urination, new swelling, unusual tiredness, nausea, or changes in how you feel. Early reporting allows dose changes or a switch of therapy.

Hearing and Balance Warning

Ototoxicity

Ototoxicity can cause hearing loss, ringing in the ears (tinnitus), or vertigo. Symptoms may not appear until after therapy ends, and the damage may be permanent. This is one of the most important reasons Zemdri is reserved for specific situations.

Baseline and Follow-Up

Care teams may check hearing at baseline or during treatment, especially for patients on longer courses or with prior hearing problems. Tell your clinician about any hearing change, even if it seems minor.

Balance Symptoms

Dizziness or unsteadiness can also signal inner-ear involvement. Report these symptoms promptly.

Neuromuscular Blockade and Pregnancy Warnings

Neuromuscular Blockade

Aminoglycosides can interfere with nerve signals to muscles. Symptoms can include muscle weakness, difficulty breathing, or trouble with swallowing. This risk is higher with certain medical conditions, neuromuscular disorders, or medications that affect neuromuscular function. Anyone with weakness or breathing trouble during treatment needs urgent evaluation.

Fetal Harm

The boxed warning includes fetal harm. Aminoglycosides can cause hearing loss in infants exposed in the womb. Zemdri should generally be avoided in pregnancy unless the potential benefit clearly outweighs the risk, and any pregnant patient should discuss options with her obstetric and infectious disease teams.

Breastfeeding

Discuss breastfeeding with your care team before treatment. Decisions depend on the drug's transfer into milk and the infant's age and health.

Other Side Effects

Common Reactions

Nausea, vomiting, headache, and changes in blood pressure have been reported in clinical summaries. Infusion-related reactions can occur. Most are manageable, but they should be reported.

Infection Risk

Like other antibiotics, Zemdri can trigger Clostridioides difficile infection, which causes persistent or bloody diarrhea. Report diarrhea promptly, because C. difficile needs its own treatment.

Allergic Reactions

Hypersensitivity reactions can occur. Rash, facial swelling, trouble breathing, or fainting are emergencies requiring immediate care.

Who Should Not Receive Zemdri

Known Allergy

People with a known allergy to plazomicin or other aminoglycosides should not receive Zemdri. Your team will review your allergy history before treatment.

Kidney or Hearing Problems

Patients with significant kidney disease or existing hearing loss need careful assessment. The benefit must be weighed against the risk of further harm, and alternatives may be preferred.

Pregnancy

Because of the fetal harm warning, pregnancy is an important consideration, and the decision requires specialist input.

Drug Interactions

Nephrotoxic Drugs

Combining Zemdri with other drugs that harm the kidneys raises the risk of kidney injury. These include certain antibiotics such as vancomycin, some diuretics, NSAIDs, and contrast agents used for imaging. Your team should review every medication.

Ototoxic and Neuromuscular Drugs

Other drugs that affect hearing or nerve-muscle function can add to Zemdri's risks. Loop diuretics and neuromuscular blocking agents are examples that clinicians consider carefully.

Medication Review

Give your care team a complete list of prescriptions, over-the-counter medicines, and supplements. Pharmacists check for interactions before starting therapy.

How Zemdri Compares With Other Options

Carbapenems

Carbapenems such as meropenem and ertapenem remain the usual choice for many resistant gram-negative infections. Zemdri was compared with meropenem in EPIC. Clinicians may consider Zemdri when carbapenems are not suitable, but overuse of either drug accelerates resistance.

Older Aminoglycosides

Gentamicin and amikacin carry similar kidney and ear risks, and many organisms resist them. Zemdri's main advantage is its activity against many isolates resistant to older aminoglycosides.

Oral Options

For uncomplicated infections, oral antibiotics are usually preferred. Newer oral options exist for some complicated UTIs, which is why clinicians choose based on culture results, severity, and patient factors.

Antibiotic Stewardship

Preserving Effectiveness

Antibiotics lose value when they are used too broadly. Zemdri is intended for resistant infections where alternatives are limited, which helps preserve its usefulness.

Culture First

Urine and blood cultures with susceptibility results should guide therapy. Clinicians should document why an aminoglycoside was chosen and review the regimen as results return.

Reporting Resistance

Unexpected resistance patterns should be reported to infection prevention teams and public health authorities.

Availability and Cost

Availability

Zemdri is intended for hospital and infusion settings, and availability depends on the facility. Your care team can confirm whether it is stocked or can be obtained.

Cost

Pricing for hospital IV antibiotics is complex, and drug prices change over time. A 2019 pharmacy analysis listed an average wholesale price of about $378 per 10 mL vial, but current prices may differ. Ask your insurer or hospital financial counselor for up-to-date figures.

Insurance Coverage

Coverage for FDA-approved indications is generally more straightforward. Prior authorization may be required, and your pharmacy team can help with the paperwork.

Questions to Ask Your Care Team

• Did my culture show a susceptibility to plazomicin, and what other options exist?
• How will my kidney function and drug levels be checked?
• Should I have a hearing test before or during treatment?
• What symptoms should make me call right away?
• Are any of my current medications a concern with this drug?
• How long will I need treatment, and what happens after I finish?

Frequently Asked Questions

Q: What is Zemdri used for?

A: Zemdri is approved for adults with complicated urinary tract infections, including pyelonephritis, caused by certain Enterobacterales when there are limited or no other options.

Q: When was Zemdri approved?

A: The FDA approved it on June 25, 2018.

Q: Is Zemdri a pill?

A: No. It is given only by IV infusion.

Q: Does Zemdri cause hearing loss?

A: It can. Ototoxicity, including hearing loss, tinnitus, or vertigo, is in the boxed warning, and it may be permanent. Report any hearing change promptly.

Q: Can Zemdri hurt my kidneys?

A: Yes. Nephrotoxicity is in the boxed warning, and risk is higher with existing kidney disease or other nephrotoxic drugs. Monitoring is essential.

Q: Is Zemdri approved for bloodstream infections?

A: No. The FDA approved it only for complicated urinary tract infections.

Q: Is Zemdri safe in pregnancy?

A: The label carries a fetal harm warning. Pregnant patients should discuss options with their care team before any decision.

Medical Disclaimer

This article is for general education only and does not provide medical advice, diagnosis, or treatment. Complicated urinary tract infections require evaluation by a qualified clinician, and Zemdri is given only in healthcare settings. Do not start, stop, or change any antibiotic without guidance from your care team. For dosing, monitoring, and safety information, consult the current U.S. prescribing information. If you have fever with chills, back or flank pain, confusion, reduced urine output, or difficulty breathing, seek emergency care immediately.

Sources and Further Reading

• ZEMDRI (plazomicin) U.S. Prescribing Information, including the boxed warning on nephrotoxicity, ototoxicity, neuromuscular blockade, and fetal harm
• Drugs.com Zemdri FDA approval history (approval date June 25, 2018)
• Achaogen press release on FDA approval of ZEMDRI, June 26, 2018
• Achaogen press release on the commercial launch of ZEMDRI, which gives the June 25, 2018 approval date
• Pennsylvania Society of Health-System Pharmacists analysis of plazomicin for cUTI (EPIC trial summary)
• Published review of plazomicin activity against metallo-beta-lactamase-producing Enterobacteriaceae
• Clinical summary of plazomicin nephrotoxicity and trough-level relationship

This article reflects information available as of October 2026. Confirm current prescribing details with your healthcare provider and the latest FDA labeling. For more on antibiotic options, visit MyOnlineMedShop blog or contact us.