Linezolid as a potential alternative to glycopeptide in treating Enterococcus faecium suspected cyst infection in a hemodialysis patient with autosomal-dominant polycystic kidney disease: A case report

Introduction

Autosomal-dominant polycystic kidney disease (ADPKD) is the most common form of polycystic kidney disease and is typically an adult-onset multisystem disorder characterized by progressive renal cyst formation. ¹ In Japan, ADPKD is classified as an intractable disease and has traditionally been estimated to affect approximately 1 in 4000 individuals. ² More recent epidemiological studies have suggested a higher prevalence of approximately 6.8 per 10,000 individuals, indicating that ADPKD may be underdiagnosed in the general population. ³ Globally, ADPKD is the most common hereditary kidney disease. However, high-quality evidence to guide its clinical management remains limited. Among its complications, renal cyst infection represents a distinctive and clinically significant infectious manifestation that poses considerable diagnostic and therapeutic challenges.^2,4,5 In patients receiving maintenance hemodialysis for more common causes of end-stage kidney disease, such as diabetic nephropathy, infections typically involve the respiratory or urinary tract, and antibiotic selection is generally determined based on pathogen susceptibility, residual renal function, and drug tissue penetration. In contrast, cyst infections in ADPKD represent a particularly complex therapeutic problem because of the limited availability of evidence-based recommendations and poor intracystic penetration of several antimicrobial agents. ² These challenges are further amplified in patients undergoing hemodialysis, in whom impaired renal function restricts antibiotic options, particularly when glycopeptide antibiotics such as vancomycin are contraindicated due to allergy or intolerance.

In this report, we describe a case of suspected cyst infection in a patient with ADPKD, in whom glycopeptide therapy was ineffective or contraindicated, and linezolid was successfully administered. This case highlights key considerations in antibiotic selection in this complex clinical setting.

Case presentation

An 81-year-old Japanese man with ADPKD undergoing maintenance hemodialysis three times weekly had a medical history of cerebral aneurysm, hemorrhoids, erythroderma secondary to eczema, hepatitis B, hypertension, and a thyroid mass. Hemodialysis was performed via a long-term tunneled cuffed catheter placed in the left internal jugular vein. He had previously received multiple courses of antibiotics for recurrent suspected cyst infections since 2014. In early April 2024, he was admitted to our hospital with a body temperature of 38.6°C. On examination, his pulse rate was 64 beats/min, blood pressure was 148/86 mmHg, respiratory rate was 18 breaths/min, and oxygen saturation was 98% on room air.

Chest and pelvic computed tomography (CT) revealed multiple hepatic and renal cysts without evidence of focal inflammatory changes or alternative sources of infection. Laboratory test results showed mildly elevated inflammatory markers, including C-reactive protein (CRP) at 2.11 mg/dL and procalcitonin at 0.17 mg/dL, without leukocytosis (white blood cell count, 6.97 × 10³/µL). Other sources of infection, including vascular catheter-related infection, endocarditis, and acute pyelonephritis could not be entirely excluded. However, no clinical signs suggestive of exit-site or tunnel infection, such as erythema, tenderness, or discharge, were identified to support catheter-related bloodstream infection. Empirical intravenous levofloxacin (LVFX) at 500 mg/day was initiated on day 1 (Figure 1). On day 4, blood cultures yielded Enterococcus faecium (E. faecium) susceptible to glycopeptides but resistant to LVFX (Table 1). Although infective endocarditis was considered given the presence of E. faecium, no clinical features suggestive of endocarditis, such as new cardiac murmurs or embolic phenomena, were observed, but echocardiography was not performed. In addition, acute pyelonephritis was less likely because urinalysis and urine culture were negative, and the patient did not exhibit urinary symptoms such as dysuria or flank pain. Therefore, recurrent cyst infection was suspected although it could not be definitively confirmed, based on his previous history of suspected cyst infection and the absence of additional symptoms or significant physical findings. The clinical diagnosis and treatment strategy were determined through multidisciplinary discussion involving a nephrologist and the antimicrobial stewardship team, with input from pharmacists.

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Figure 1.

Clinical course of the patient, including BT, CRP, and WBC. Day 1 was defined as the day of hospital admission. Serial measurements of BT, CRP, and WBC are shown over time. The upper panel indicates the timing and dosage of levofloxacin, teicoplanin, and linezolid (600 mg every 12 h). Levofloxacin was initiated on day 1, followed by teicoplanin on day 4 and linezolid on day 12. Arrows indicate the timing of hemodialysis sessions at three times weekly.

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Table 1.

Antibiotic susceptibility of the Enterococcus faecium isolate from the patient before antibiotic treatment ^a .

Antibiotic class	Drug tested	MIC (μg/mL) of isolate in blood	Interpretation
Beta-lactams	PCG	>8	R
	ABPC	>8	R
	ABPC/SBT	>16	R
Quinolones	LVFX	>4	R
Others	VCM	⩽0.5	S
	TEIC	⩽2	S
	LZD	2	S

MIC: minimum inhibitory concentration; PCG: penicillin G; ABPC: ampicillin; SBT: sulbactam; LVFX: levofloxacin; VCM: vancomycin; TEIC: teicoplanin; LZD: linezolid; R: resistant; S: susceptible.

a

Bold text indicates the antimicrobials used for successful treatment of the patient.

Given his allergy to vancomycin, intravenous teicoplanin was administered at 600 mg every 12 h on days 4 and 5, followed by 300 mg on day 6, and 200 mg on days 8, 9, and 12, in accordance with therapeutic drug monitoring guidance. ⁶ The pre-dialysis trough concentration of teicoplanin on day 7 was 31.9 μg/mL, within the therapeutic range. Despite adequate drug levels, fever (37.9 °C) and elevated CRP levels (9.65 mg/dL) persisted, and repeated blood cultures on day 12 remained positive for E. faecium. Given the lack of clinical response, oral linezolid (600 mg every 12 h) was initiated on day 12. By day 19, his body temperature and CRP levels had improved (36.8 °C and 2.20 mg/dL, respectively). Linezolid was discontinued after 15 days of therapy (on hospital day 27) due to grade 1 thrombocytopenia according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0⁷ (the platelet count decreased from 192 × 10³/μL before linezolid initiation on day 12 to 101 × 10³/μL on day 26). Repeat blood cultures became negative on day 21, confirming bacteremia clearance, and the patient was discharged on day 30 in a stable condition with normal inflammatory markers. The patient remained clinically stable for 3 months after discharge, with no recurrence of fever or elevation of inflammatory markers, supporting the diagnosis of a suspected cyst infection. In addition, no recurrence of E. faecium infection was observed during subsequent clinical follow-up. This case report was reported in accordance with the CARE guideline (Supplemental Material).

Discussion

Herein, we describe a case of suspected cyst infection caused by glycopeptide-susceptible E. faecium in a patient with ADPKD undergoing maintenance hemodialysis, which improved with linezolid after treatment failure with glycopeptide-antibiotics.

Renal cyst infections originate from either the ascending urinary tract or hematogenous spread. ⁸ ADPKD with fever, acute abdominal or flank pain, and an increased white blood cell count and/or CRP level should undergo imaging tests for confirmation of kidney cyst infection. ⁹ In this case, a definitive diagnosis of cyst infection was not established because advanced imaging modalities, such as fluorine-18 fluorodeoxyglucose–positron emission tomography ([¹⁸F]FDG–PET)/CT and diffusion-weighted magnetic resonance imaging (MRI), were not performed. These modalities are considered useful for improving diagnostic accuracy in cyst infections associated with ADPKD. ¹⁰ However, PET/CT is generally limited to the evaluation of malignancies in Japan due to restricted insurance coverage. Diffusion-weighted MRI was also not performed because there were no focal clinical findings suggestive of localized infection that would warrant additional imaging beyond CT. Therefore, the diagnosis was based on clinical presentation, history of recurrent suspected cyst infections, and exclusion of other potential sources of infection. In addition, in this case, alternative sources of infection, including catheter-related bloodstream infection, infective endocarditis, and acute pyelonephritis, were carefully considered. These conditions could not be completely excluded because paired peripheral and catheter blood cultures and catheter tip cultures were not obtained, which limited definitive exclusion of catheter-related bloodstream infection. However, no clinical signs suggestive of catheter-related infection were identified, such as exit-site inflammation, and no features indicative of infective endocarditis, including cardiac murmurs or embolic phenomena. Furthermore, urinalysis and urine culture were negative, and the patient did not present with urinary symptoms, making acute pyelonephritis less likely. Therefore, cyst infection was considered the most plausible diagnosis based on clinical presentation, previous history of recurrent suspected cyst infections, and the absence of other identifiable infection sources. In addition, the relatively modest elevation of inflammatory markers despite high fever may be partly explained by uremia-associated immune dysregulation in patients undergoing hemodialysis and by the anatomically sequestered nature of cyst infections in ADPKD.

Renal cyst infections may persist despite appropriate antibiotic therapy owing to antimicrobial resistance and poor intracystic drug penetration, ² and most commonly involve gram-negative enteric organisms. ¹¹ Current treatment strategies favor lipid-soluble agents with good cyst penetration, such as fluoroquinolones (e.g. LVFX). E. faecium, a gram-positive coccus, is also a causative pathogen and is often difficult to treat because of intrinsic and acquired antibiotic resistance. ¹² E. faecium has also been reported as a causative pathogen of cyst infections, ¹¹ although it is less common than gram-negative organisms. In addition, infections due to Enterococcus species may occur more frequently in immunocompromised conditions, including in patients undergoing hemodialysis. Glycopeptide antibiotics, such as vancomycin, are often used to treat general infectious diseases caused by glycopeptide-susceptible E. faecium. ¹³ However, because these agents are hydrophilic, their penetration into renal cysts in ADPKD may be limited, particularly in non-leaky cysts that do not communicate with renal tubules. In such cysts, drug delivery may occur independently of glomerular filtration, potentially reducing intracystic concentrations of hydrophilic antibiotics.^14,15

Linezolid, an oxazolidinone antibiotic, could be an effective alternative in patients with an allergy or intolerance to glycopeptides, such as vancomycin and teicoplanin, for the treatment of glycopeptide-susceptible E. faecium bloodstream infections. ¹⁶ Additionally, because linezolid is primarily metabolized hepatically and does not require routine dose adjustment in renal impairment, it may be advantageous in patients receiving maintenance hemodialysis. Furthermore, linezolid may be superior to water-soluble glycopeptide antibiotics for the treatment of renal cyst infections because lipid-soluble antibiotics demonstrate good cyst penetration. ¹⁰ Linezolid has favorable target tissue penetration and a larger volume of distribution than glycopeptide antibiotics because of its liposolubility, small molecular weight, and lower protein binding. ¹⁷ Therefore, linezolid may be considered an antibiotic for cyst infections caused by glycopeptide-susceptible E. faecium.

Prolonged antibiotic therapy (typically 4–6 weeks) is generally recommended in the management of cyst infections. However, linezolid-associated thrombocytopenia is a well-recognized adverse event, and its incidence has been reported to be higher in patients with renal impairment. ¹⁸ Although linezolid is primarily metabolized via non-renal pathways, pharmacokinetic studies have reported increased systemic exposure in patients with renal impairment, including those undergoing hemodialysis.^19,20 This increased exposure may contribute to hematologic toxicity, such as thrombocytopenia and pancytopenia, and has also been associated with other adverse events. In the present case, grade 1 thrombocytopenia, according to the CTCAE, was observed during linezolid therapy, which led to discontinuation of treatment after 15 days. However, no recurrence of E. faecium infection was observed during subsequent clinical follow-up. Therefore, linezolid may have contributed to suspected cyst infections caused by E. faecium in patients with ADPKD undergoing maintenance hemodialysis. In addition, extended linezolid therapy has been associated with the development of resistance in E. faecium. ²¹ Therefore, short-term oral administration is preferable when linezolid is selected as an antibiotic for use in treating cyst infections caused by E. faecium.

This study had several limitations. First, a definitive diagnosis of cyst infection could not be established because advanced diagnostic evaluations, including [¹⁸F]FDG–PET/CT, diffusion-weighted MRI, cyst fluid aspiration, and echocardiography, were not performed. In addition, the primary source of bacteremia could not be definitively identified. Although suspected cyst infection was considered the most plausible diagnosis, alternative infection sources, including catheter-related bloodstream infection, could not be completely excluded. Therefore, this case should be interpreted as a suspected cyst infection. Second, the serum and cyst fluid concentrations of linezolid were not measured, as therapeutic drug monitoring is not routinely performed in clinical practice. Nevertheless, the favorable clinical response suggests potential effectiveness without pharmacokinetic confirmation.

Conclusion

This case highlights linezolid as a potential alternative for suspected cyst infections caused by E. faecium, particularly when glycopeptide therapy is ineffective or contraindicated. Although glycopeptide antibiotics are often considered for such infections, their use in patients undergoing hemodialysis is known to be challenging owing to complex dosing and monitoring requirements. In this case, the source of infection could not be definitively established, and it remained unclear whether the infection originated from cysts or renal parenchyma. Despite this limitation, this case contributes to the limited clinical evidence on the management of suspected cyst infections in ADPKD and may support the use of linezolid in similar clinical settings.

Supplemental Material