Background

Colistin, also known as polymyxin E, is a polypeptide antibiotic that has regained clinical importance in recent years due to the increasing prevalence of carbapenem-resistant Gram-negative bacterial (CR-GNB) infections. Polymyxin B is a close agent in the same polymyxin class, but is pharmacokinetically and structurally distinct. Unlike colistin, which is administered as an inactive prodrug, polymyxin B is given in its active form and achieves rapid peak plasma concentrations and is widely used in clinical practice in China.1 These pharmacokinetic differences are clinically relevant.2 Colistin methanesulfonate requires in vivo conversion to the active form, and both the prodrug and the active drug are primarily cleared by the kidneys, resulting in delayed and variable exposure.3 In contrast, polymyxin B is predominantly cleared by non-renal pathways, leading to more predictable plasma concentrations.1 Both agents exhibit potent activity against carbapenem-resistant Acinetobacter baumannii (CRAB) infections. However, adverse drug reactions associated with polymyxins, particularly nephrotoxicity and neurotoxicity, remain significant limitations to their clinical use.4,5

In addition to these well-recognized adverse effects, polymyxin therapy has been associated with muscle injury. The proposed mechanism involves the polycationic nature of polymyxins, which may interact with eukaryotic cell membranes, disrupt mitochondrial function, and increase membrane permeability, leading to the release of intracellular contents such as MB.6,7 This type of drug-induced muscle injury can present with a wide range of CK levels, from normal to markedly elevated, and MB may be a more sensitive early marker than CK.8 Although the exact incidence is unknown, cases of polymyxin B-associated muscle injury remain rarely reported, and clinical awareness of this adverse reaction is limited.9,10

Here, we report a case of polymyxin B-associated muscle injury with marked MB elevation, aiming to enhance clinical awareness of this rare adverse reaction.

Case Presentation

A 63-year-old woman, with a history of hypertension, type 2 diabetes mellitus, rheumatic heart disease, valvular heart disease and auricular fibrillation, was admitted to our hospital.

On October 7, 2025, she presented with sudden loss of consciousness lasting one hour and was diagnosed with cerebral embolism. She underwent mechanical thrombectomy for acute cerebral infarction at an outside hospital. Postoperatively, she developed intracerebral hemorrhage, which required subsequent decompressive craniectomy and right ventricular drainage. Following this, she developed a progressively worsening pulmonary infection accompanied by recurrent high fever. Due to poor sputum drainage and difficulty maintaining oxygen saturation, a tracheotomy was performed. Sputum culture showed extensive drug resistant Acinetobacter baumannii (XDR-AB), susceptible to tigecycline and colistin and blood culture revealed Bacillus cereus, susceptible to vancomycin. Her condition improved after treatment with vancomycin, polymyxin B and tigecycline.

On October 23, 2025, the patient was transferred to our hospital for further rehabilitation. At admission, she was unconscious and in a tracheostomized state. The cranial surgical wound showed poor healing, with a 3×2 cm ulcerated area covered with purulent secretions. Laboratory tests revealed elevated inflammatory markers: white blood cell (WBC) count 16 × 109/L (reference range 3.5–9.5 × 109/L), neutrophil percentage 89.9% (reference range 40–75%), C-reactive protein (CRP) 29.76 mg/L (reference range<10 mg/L), and procalcitonin (PCT) 0.50 ng/mL (reference range<0.1ng/mL). Baseline serum creatinine (SCr) was 70 μmol/L (reference range 44–106 μmol/L). CK and MB levels were mildly elevated: CK 180 U/L (reference range 40–200 U/L), MB 391 μg/L (reference range <70 μg/L). Coagulation parameters showed fibrinogen 3.84 g/L (reference range 2–4 g/L), prothrombin time (PT) 15.20 s (reference range 9–12.5 s) and activated partial thromboplastin time (APTT) 40.80 s (reference range 25–34 s).

On the second day after admission (October 24), the patient developed a high fever (38.9°C) with prominent pulmonary crackles. Based on previous microbiological findings and antimicrobial susceptibility results, the antimicrobial regimen was continued as follows: tigecycline 50 mg intravenously every 12 h (loading dose 100 mg), polymyxin B 75 mg (750,000 IU) intravenously every 12 h combined with polymyxin B inhalation 25 mg (750,000 IU) every 12 h, and vancomycin 1 g intravenously every 12 h. The antimicrobial susceptibility testing results for the hospitalized patients are presented in Table 1.

Table 1 Antimicrobial Susceptibility Results of Acinetobacter baumannii Isolated at Our Hospital

During treatment, body temperature gradually decreased, WBC count dropped, and CRP slightly increased to 50.27 mg/L, while PCT rose to 4.68 ng/mL. Blood cultures became negative. However, renal function and muscle injury markers progressively worsened. On hospital day 15 (November 6), SCr increased to 178 μmol/L, CK increased to 332 U/L, and MB markedly increased to 9002.40 μg/L. Coagulation abnormalities were also observed, including a decrease in fibrinogen to 1.57 g/L (a 59.1% decrease from baseline), prolonged PT of 16.50 s, and prolonged APTT of 60.8 s. These findings suggested muscle injury, accompanied by acute kidney injury and coagulation abnormalities.

After excluding trauma, worsening infection, and the independent effects of other medications, and considering the temporal relationship with drug exposure, as well as the Naranjo adverse drug reaction probability scale and the WHO-Uppsala Monitoring Centre (WHO-UMC) causality categories, polymyxin B-induced rhabdomyolysis with drug-related kidney injury was regarded as the probable diagnosis.11 The decrease in fibrinogen was likely associated with tigecycline therapy.

On November 7, Polymyxin B, tigecycline and vancomycin were immediately discontinued, and the antimicrobial regimen was adjusted to meropenem 2 g intravenously every 8 hours via extended infusion (over 2 hours). Following the discontinuation, MB and CK levels began to decline. Supportive treatment was initiated, including aggressive isotonic crystalloid fluid resuscitation (maintaining urine output >3000 mL/d), sodium bicarbonate infusion for urine alkalinization and correction of electrolyte imbalance.

On November 14, eight days after polymyxin B discontinuation, laboratory results showed a decrease in MB to 1550 μg/L, CK to 101 U/L, SCr to 112 μmol/L. Two weeks later, on November 21, laboratory tests revealed further improvements: MB decreased to 171 μg/L, CK to 45 U/L, and SCr to 76 μmol/L. No severe complications, such as acute renal failure or arrhythmia, occurred, and the infection was effectively controlled. The temporal trends of CK and MB levels are shown in Figure 1.

Figure 1 Temporal trends of MB and CK levels during polymyxin B therapy.

Abbreviations: CK, creatine kinase; MB, myoglobin.

Discussion

We describe a case of polymyxin B-associated muscle injury in a critically ill patient treated for XDR-AB infection. After receiving polymyxin B in combination with vancomycin and tigecycline, the patient developed marked MB elevation (peak 9002.4 μg/L) with only a modest rise in CK (332 U/L) and progressive renal dysfunction (creatinine 70 to 178 μmol/L). Following drug discontinuation, these abnormalities gradually resolved. Similar cases of polymyxin B-associated muscle injury have been reported in both the English and Chinese literature.9,10

The key laboratory finding in this case was the discordance between MB (9002.4 μg/L) and CK (332 U/L). MB (~17.8 kDa) is a small cytoplasmic protein, whereas CK (~82 kDa) is a larger dimeric enzyme. In acute, reversible membrane injury rather than full necrosis, small proteins can leak out through transient membrane pores while larger enzymes remain intracellular.12,13 Ostrowski et al noted that MB may be a more sensitive marker of drug-induced muscle injury than CK.8 Valiyil et al also observed that CK levels in drug-induced myopathies span a wide range, and a normal CK does not rule out muscle injury.6 Polymyxin B interacts with eukaryotic cell membranes due to its polycationic nature. It causes mitochondrial fragmentation, loss of membrane potential, and reactive oxygen species generation.7 These effects may increase muscle cell membrane permeability and allow preferential release of small molecules such as MB. This may explain why MB reached 128 times the upper limit of normal while CK rose only modestly. Even without a marked CK elevation, MB can trigger acute kidney injury through renal vasoconstriction, intratubular cast formation, and direct cytotoxicity.14,15 In this case, the parallel changes in creatinine and MB after drug withdrawal support this relationship.

Several factors could have contributed to muscle injury and renal dysfunction. Prolonged immobilization following cerebral embolism surgery may have caused background muscle catabolism. The patient also had severe polymicrobial infections with high fever, but infection markers improved while MB continued to rise until polymyxin B was stopped, suggesting infection alone was not the primary cause. Vancomycin does not cause direct muscle damage, but its nephrotoxicity is well documented and may have contributed to the overall AKI risk when combined with polymyxin B.4,16 It is possible that vancomycin-induced kidney injury further reduced MB clearance and slowed polymyxin B elimination, creating a cascade that amplified muscle toxicity. Fibrinogen declined from 3.84 g/L to 1.57 g/L during tigecycline therapy, a pattern commonly seen with this drug.17 However, the addition of tigecycline to polymyxin B does not increase the risk of AKI beyond polymyxin B alone, suggesting tigecycline is not an independent contributor to nephrotoxicity.18 In summary, the muscle injury was multifactorial, with polymyxin B as a modifiable trigger rather than the sole cause. The causality assessment using the Naranjo scale and WHO-UMC criteria indicated that polymyxin B was the most likely causative agent. However, these tools have inherent limitations in complex clinical settings where multiple medications and underlying disease are present. The “probable” classification should be interpreted with caution.

This case highlights several points for clinical practice. First, high-risk patients include those with pre-existing renal impairment, those receiving concomitant nephrotoxic agents such as vancomycin, and those receiving polymyxin B via both intravenous and inhaled routes. Second, monitoring should include CK and MB in addition to renal function, as MB may rise substantially even when CK is only mildly elevated.

This case has several limitations. The patient received multiple medications and had serious infections, making it difficult to isolate the cause of muscle injury in a single case. Other causes of muscle injury cannot be excluded. In addition, therapeutic drug monitoring for polymyxin B was not performed, so we cannot distinguish whether muscle injury occurred at therapeutic drug levels or from drug accumulation. The patient’s impaired consciousness prevented assessment of myalgia or muscle weakness. Finally, this report describes a single patient, and the findings should be interpreted cautiously and confirmed in further studies.

Data Sharing Statement

The raw data supporting the conclusions of this article are available from the corresponding author, Chujuan Liu ([email protected]), upon reasonable request, without undue reservation.

Ethical Statement

This case report was conducted in accordance with the ethical guidelines of the Helsinki Declaration and was approved by the Medical Ethics Review Committee of Hunan Provincial People’s Hospital (The First Affiliated Hospital of Hunan Normal University) (Approval No. LL-20260407-130). The patient described in this case report has a cognitive impairment and lacked the capacity to provide informed consent. Therefore, written informed consent was obtained from the patient’s legal guardian.

Consent for Publication

Written informed consent for publication was obtained from the patient’s legal guardian.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Funding

This work was supported by funding of the Key Talent Project of Gansu Province (Grant number: 2026SWJWRC001).

Disclosure

The authors declare no competing interests.

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