Rapid Succession of Multidrug-Resistant Bacteremia and Candidemia in a Patient with Refractory Pemphigus Vulgaris: A Lethal Therapeutic Challenge

Abstract

Background

Immunosuppressed patients with extensive skin barrier disruption face extraordinary risks for polymicrobial infections. The rapid, sequential emergence of multidrug-resistant (MDR) bacteremia and candidemia in such hosts constitutes a particularly lethal complication with limited therapeutic options.

Case Presentation

We report a 74-year-old woman with refractory pemphigus vulgaris (PV), type 2 diabetes mellitus, and chronic obstructive pulmonary disease who developed a cascade of MDR infections over a 14-day hospitalization. Following initial methicillin-resistant Staphylococcus aureus (MRSA) skin colonization, she developed Serratia marcescens bacteremia, subsequently complicated by wound superinfection with carbapenem-resistant Acinetobacter baumannii (CRAB) and multiple Candida species, including the rare yeast Kodamaea ohmeri. Despite sequential antimicrobial escalation—from piperacillin-tazobactam/linezolid to meropenem/amikacin, and finally caspofungin—her condition deteriorated with diabetic ketoacidosis, culminating in the family’s decision to pursue discharge with comfort care based on the patient’s previously expressed wishes; she died three days later. K. ohmeri demonstrated reduced fluconazole susceptibility (MIC = 8 µg/mL), highlighting the diagnostic and therapeutic challenges posed by emerging fungal pathogens.

Conclusion

This case starkly illustrates the catastrophic potential of rapid, sequential MDR infections in profoundly immunocompromised hosts with skin barrier defects. It underscores the critical importance of early microbiological surveillance, the clinical urgency of dynamic antimicrobial stewardship, and the imperative for multidisciplinary management to navigate the irreconcilable conflict between necessary immunosuppression and life-threatening infection.

Introduction

The global spread of multidrug-resistant (MDR) organisms represents a paramount challenge in infectious disease management, particularly among vulnerable populations.¹ Immunocompromised patients with compromised skin barriers face unparalleled susceptibility to severe, polymicrobial, and MDR infections.² Pemphigus vulgaris (PV), an autoimmune blistering disease necessitating potent immunosuppression, exemplifies this high-risk profile.³

While Staphylococcus aureus remains a well-recognized pathogen in PV, infections caused by MDR Gram-negative bacilli and fungi are increasingly documented and associated with worse outcomes.⁴ Serratia marcescens and carbapenem-resistant Acinetobacter baumannii (CRAB) are of particular concern due to their formidable intrinsic and acquired resistance profiles, frequently leaving few effective therapeutic options.^5,6 Recent surveillance data demonstrate that CRAB resistance rates exceed 70% in intensive care units globally, with immunocompromised status identified as an independent risk factor for CRAB infection.⁷ Fungal superinfections, particularly those involving non-albicans Candida species and rare emerging yeasts such as Kodamaea ohmeri, add further complexity in patients receiving broad-spectrum antibiotics and corticosteroids.^8,9

To our knowledge, this is the first reported case of rapid sequential MDR bacteremia and candidemia involving K. ohmeri in a patient with PV, providing novel insights into the diagnostic and therapeutic challenges of emerging fungal pathogens in this population. Here, we present a fatal case of refractory PV complicated by a rapid, sequential onslaught of MDR bacteremia and candidemia—a clinical scenario that exemplifies the extreme infection risks in this population and offers critical lessons for antimicrobial stewardship and multidisciplinary care.

Case Presentation

A 74-year-old Chinese woman presented with a 2-month history of widespread bullae and erosions covering approximately 60% of her body surface area. Her medical history included poorly controlled type 2 diabetes mellitus (HbA1c 9.8%) and chronic obstructive pulmonary disease. She had a 20-pack-year smoking history but quit 10 years prior. She denied alcohol or illicit drug use and had no specific occupational exposures. She had previously received rituximab and mycophenolate mofetil for PV control, with limited response. Her corticosteroid regimen prior to admission was oral prednisone 40 mg/day for 3 months.

Physical examination revealed extensive flaccid bullae and erosions on the face, trunk, and extremities, with a positive Nikolsky sign and oral mucosal involvement (Figure 1). Skin biopsy demonstrated suprabasal acantholysis, and direct immunofluorescence showed intercellular IgG and C3 deposition, confirming PV diagnosis.

Figure 1.

Clinical presentation at admission showing extensive flaccid bullae and erosions on the face, trunk, and extremities, with a positive Nikolsky sign and oral mucosal involvement.

Hospital Course and Microbiological Findings

Days 1–2 (ICU admission): She was admitted for a severe PV flare and treated with intravenous methylprednisolone (1 mg/kg/day) and intravenous immunoglobulin (IVIG, 400 mg/kg/day for 5 days). Initial wound cultures grew methicillin-resistant Staphylococcus aureus (MRSA).

Days 3–7: She developed fever (39.2°C) and hypotension (85/50 mmHg). Blood cultures yielded Serratia marcescens, susceptible to meropenem, ceftazidime, and amikacin. The initial empiric regimen was piperacillin-tazobactam (4.5 g q6h, IV) and linezolid (600 mg q12h, IV). Antimicrobial therapy was then escalated to meropenem (2 g every 8 h) and amikacin (15 mg/kg/day). On day 7, the skin condition showed partial healing of some lesions but also the appearance of new bullae (Figure 2).

Figure 2.

Skin condition on hospital day 7. Areas of partial re-epithelialization are visible, along with the appearance of new bullae, indicating ongoing disease activity.

Days 8–12: Persistent fever prompted repeat wound cultures, which grew CRAB and multiple Candida species (C. albicans, C. tropicalis). Caspofungin (70 mg loading dose, then 50 mg/day) was added. She developed diabetic ketoacidosis (blood glucose 28 mmol/L, pH 7.18, serum ketones positive), requiring intensive insulin therapy and fluid resuscitation.

Days 13–14: Her condition deteriorated with altered mental status (Glasgow Coma Scale 12) and persistent sepsis. The family, respecting the patient’s previously expressed wishes, opted for discharge with comfort care. At discharge on day 14, the wounds showed areas of re-epithelialization, though active infection persisted (Figure 3). She died three days later. No autopsy was performed.

Figure 3.

Skin condition at discharge (day 14). Areas of re-epithelialization are noted, though active infection persisted, as evidenced by surrounding erythema and exudate.

The patient’s clinical course, marked by sequential MDR infections, is summarized in Figure 4.

Figure 4.

Clinical timeline illustrating the sequence of infections and interventions from admission through discharge. Key events include microbial isolation, antimicrobial regimen changes, and clinical deterioration.

Microbiological and Laboratory Data

Comprehensive culture data and susceptibility profiles are presented in Table 1. Key findings included:

1. Bloodstream infection with S. marcescens (identified by VITEK^® 2 system, bioMérieux). The time-to-positivity (TTP) for blood cultures was 8 hours, suggesting high bacterial load. Bacterial susceptibility was determined by the VITEK^® 2 system using CLSI breakpoints.

2. Wound superinfections with MRSA, followed by CRAB.

3. Isolation of multiple Candida species from wounds, including the rare yeast K. ohmeri, identified by MALDI-TOF MS. Antifungal susceptibility testing (per CLSI M27-A3) for K. ohmeri showed reduced susceptibility to fluconazole (MIC = 8 µg/mL) but susceptibility to caspofungin (MIC = 0.25 µg/mL) and amphotericin B (MIC = 0.5 µg/mL). Antifungal susceptibility results were available on day 12; however, the patient’s clinical deterioration precluded a change in antifungal regimen.

4. Significant leukocytosis (WBC 15.2 × 10⁹/L), elevated inflammatory markers (CRP 76.68 mg/L, PCT 0.303 ng/mL), and metabolic acidosis consistent with diabetic ketoacidosis.

Table 1.

Microbiological Findings and Susceptibility Patterns

Specimen	Date	Organism	Key Susceptibilities	Key Resistances	Clinical Significance
Blood	2025-10-08	Serratia marcescens	Meropenem (S), Ceftazidime (S), Amikacin (S)	Piperacillin/tazobactam (treatment failure)	True bacteremia; Rapid TTP suggests high bacterial load
Wound exudate	2025-09-30	Methicillin-resistant Staphylococcus aureus (MRSA)	Linezolid (S), Tetracycline (S), Levofloxacin (S)	All β-lactams (penicillins, cephalosporins), Oxacillin	Initial skin pathogen; Community-onset healthcare-associated
Wound exudate	2025-10-12	Serratia marcescens	Amikacin (S), Meropenem (S)	Ampicillin, Amoxicillin-clavulanate	Wound colonization progressing to bacteremia
Wound exudate	2025-10-15	Acinetobacter baumannii	Amikacin (S), Colistin (S), Tigecycline (S)	Meropenem (R), Imipenem (R), Piperacillin/tazobactam (R)	Hospital-acquired MDR pathogen; wound superinfection
Wound exudate	2025-10-18	Candida albicans	Caspofungin (S, MIC ≤0.12), Fluconazole (S, MIC ≤1)	None detected	Fungal superinfection in immunocompromised host
Wound exudate	2025-10-18	Candida tropicalis	Caspofungin (S), Fluconazole (S)	None detected	Multiple Candida species co-infection
Wound exudate	2025-10-19	Kodamaea ohmeri	Caspofungin (S), Voriconazole (S)	Fluconazole (R, MIC ≥64)	Rare yeast infection in immunocompromised host
Urine	2025-10-07	Gram-negative bacilli	Not tested (screening only)	Not tested	Early indication of urinary tract involvement
Urine	2025-10-16	Serratia marcescens	Ceftazidime (S), Amikacin (S), Meropenem (S)	Ampicillin, Trimethoprim-sulfamethoxazole	Urinary tract infection/seeding from bacteremia
Urine	2025-10-20	Candida species	Caspofungin (S)	Fluconazole (species-dependent)	Candiduria in setting of systemic candidiasis
Oral mucosa	2025-10-13	Candida glabrata	Caspofungin (S), Micafungin (S)	Fluconazole (dose-dependent susceptibility, MIC 16)	Oropharyngeal candidiasis; potential source for dissemination

Therapeutic Interventions and Outcome

Management was complicated by the irreconcilable need to balance immunosuppression for PV with aggressive treatment for sepsis. High-dose methylprednisolone and IVIG were continued to control the life-threatening PV flare. Antimicrobial therapy was sequentially escalated: piperacillin-tazobactam/linezolid → meropenem/amikacin → meropenem/amikacin/caspofungin. Serum creatinine remained within normal limits (0.8–1.0 mg/dL) throughout therapy. Despite maximal supportive and targeted therapy, blood cultures remained positive for S. marcescens, and wound infections progressed. The patient died three days after discharge.

Discussion

This case starkly illustrates the vulnerability of immunocompromised patients with skin barrier defects to rapid, sequential MDR infections. The progression from MRSA to S. marcescens bacteremia, CRAB wound infection, and multi-species candidemia within 14 days underscores a confluence of risk factors: profound immunosuppression, extensive skin damage, broad-spectrum antibiotic pressure, and uncontrolled diabetes.¹⁰

The microbial succession observed is particularly instructive. S. marcescens, a healthcare-associated pathogen, likely seeded the bloodstream from colonized skin wounds.¹¹ However, molecular strain typing studies were not performed, limiting our ability to confirm clonal relatedness between wound and blood isolates. The subsequent emergence of CRAB exemplifies the selection pressure exerted by carbapenem therapy and the challenging epidemiology of this pathogen in ICU settings.⁷ Recent evidence indicates that immunocompromised status is a significant independent risk factor for CRAB acquisition, and mortality from CRAB septicemia in these patients approaches 49.5%.^7,12 Current CDC and WHO priority pathogen lists identify CRAB as a critical threat. Active surveillance screening (eg, rectal swabs) for carbapenemase-producing organisms has been recommended in high-risk settings.⁷ In patients with PV receiving immunosuppressive therapy, similar patterns of severe Gram-negative infections have been documented, underscoring the critical need for heightened vigilance.^3,13

Critically, the isolation of Kodamaea ohmeri—a rare emerging yeast with reduced fluconazole susceptibility (MIC = 8 µg/mL)—highlights the escalating risk of fungal superinfection in this context. K. ohmeri is frequently misidentified as Candida species using conventional methods, often leading to inappropriate antifungal therapy.⁸ Recent systematic reviews report that K. ohmeri infections carry a mortality rate of up to 50% in immunocompromised hosts, with fluconazole resistance documented in most clinical isolates.^9,14 Advanced identification techniques such as MALDI-TOF MS and prompt antifungal susceptibility testing are therefore essential for guiding appropriate therapy.^8,15 Notably, recent pediatric cases have demonstrated that echinocandins or amphotericin B are often more effective than fluconazole for K. ohmeri infections.¹⁶ Source control, including wound debridement, is a cornerstone of candidemia management. In this case, extensive skin involvement precluded aggressive surgical debridement, which may have contributed to therapeutic failure.

The primary therapeutic dilemma—balancing immunosuppression against infection control—was rendered nearly insurmountable by the rapid evolution of resistance. Reducing immunosuppression risked a fatal PV flare, while maintaining it impaired the host’s ability to clear infections. Similar challenges have been described in PV patients who developed severe infections during rituximab and corticosteroid therapy, where intravenous immunoglobulin was used as a bridging strategy.³

This case underscores several actionable imperatives for clinical practice:

1. Early and Repeated Microbiological Surveillance

   In high-risk patients, proactive cultures (blood, wound, respiratory) upon admission and serially are essential to establish baseline colonization and guide timely, appropriate empirical therapy. Delayed diagnosis in PV patients has been associated with unnecessary antimicrobial exposure, predisposing to colonization with MDR organisms.³

2. Dynamic Antimicrobial Stewardship

   While broad initial coverage may be necessary, rapid de-escalation based on culture and susceptibility data is crucial to minimize further resistance selection. The emergence of CRAB and K. ohmeri during therapy underscores the need for continuous reassessment. Recent studies have demonstrated that definitive regimens containing cefoperazone/sulbactam may offer survival benefits in CRAB bacteremia.¹² Guidelines from IDSA/ESCMID for MDR Gram-negative infections provide a framework for managing such cases and should be consulted in similar clinical scenarios.¹⁷

3. Multidisciplinary Collaboration

   Close collaboration between dermatology, infectious diseases, clinical microbiology, endocrinology, and intensive care teams is vital from admission for integrated decision-making. A multidisciplinary approach has been emphasized in recent PV case reports as essential for managing the competing risks of immunosuppression and infection.³

4. Aggressive Control of Modifiable Risk Factors

   Strict glycemic control is paramount, as hyperglycemia directly impairs immune function and wound healing.¹⁸

Study Limitations

This report is limited by its retrospective, single-case nature. Follow-up was truncated due to the patient’s discharge status, and autopsy confirmation was unavailable. Molecular strain typing studies were not performed, limiting our ability to confirm clonal relatedness between wound and blood isolates. Furthermore, the absence of molecular epidemiological data (eg, resistance gene sequencing, strain typing) limits insight into transmission dynamics and resistance mechanisms. These observations arise from a single case and therefore cannot establish causality.

Conclusion

This fatal case emphasizes the catastrophic potential of sequential MDR bacterial and fungal infections in immunocompromised patients with skin barrier loss. It serves as a stark reminder of the need for heightened vigilance, sophisticated antimicrobial strategies, and integrated multidisciplinary care to navigate the treacherous balance between disease control and infection in this highly vulnerable population. The recommendations derived from this case are intended to generate hypotheses for future research rather than establish evidence-based guidelines.

Funding Statement

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Declaration of Generative AI and AI-Assisted Technologies in the Manuscript Preparation Process

During the preparation of this work, the author(s) used DeepSeek in order to assist with language polishing, grammatical correction, and formatting adjustments to comply with journal guidelines. After using this tool, the author(s) reviewed and edited the content as needed and take full responsibility for the content of the published article.

Data Sharing Statement

The datasets generated during this case report are not publicly available due to patient privacy restrictions but are available from the corresponding author upon reasonable request.

Ethics Approval and Consent to Participate

Institutional review board approval was not required for this case report in accordance with the policies of Sichuan University Affiliated Chengdu Second People’s Hospital, as this study did not involve human or animal experimentation. Written informed consent for publication of this case report and any accompanying images was obtained from the patient and her legal next-of-kin. A copy of the signed consent form is available for review by the Editor-in-Chief of this journal upon request.

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.

Disclosure

The authors declare that they have no competing interests.