Providencia rettgeri and Group G Streptococcus in Anorexia Nervosa-Related Empyema: A Case Report

Introduction

Patients with anorexia nervosa (AN), a severe eating disorder primarily affecting young females, are characterized by a low body mass index (BMI), restrictive food intake patterns, intense pursuit of thinness, and profound fear of weight gain [1]. Chronic malnutrition resulting from food restriction is well-documented to suppress immune function, heightening susceptibility to a wide range of infections, including those caused by opportunistic pathogens [2]. Severe cases of AN can lead to life-threatening complications, such as opportunistic infections [3].

Empyema thoracis, the accumulation of pus in the pleural cavity, typically results from complications of bacterial pneumonia and following aspiration pneumonia. This case report describes empyema thoracis in a patient with AN, involving a polymicrobial infection caused by Providencia rettgeri, a gram-negative enterobacterium, and group G Streptococcus. The presence of these pathogens in the pleural space of an immunocompromised host, such as a patient with severe AN, presents a significant learning opportunity for clinicians and researchers [4,5].

The rarity of empyema thoracis in patients with AN and the unusual polymicrobial nature of the infection positions this case as a significant contribution to medical literature. It demonstrates the severe implications of immune suppression in AN and challenges existing paradigms regarding the management of pleural infections in highly vulnerable populations. By detailing this case, we aim to fill a notable gap in the literature, providing insights into the management and prognosis of similar cases in clinical practice and paving the way for future research into the complex interplay between chronic malnutrition, immune dysfunction, and opportunistic infections.

Case Report

A 30-year-old female woman with AN, diagnosed at 18 years of age, presented with extremity numbness and weakness. She experienced numbness from her knees to the peripheries and could not stand unassisted due to muscle weakness, requiring help for basic activities. Other AN-related symptoms included fatigue, loss of appetite, depressive state, and reduced alertness. Since her diagnosis, the patient became socially isolated, ceased working, and lived only with her mother, with her condition further isolating her from employment and social interactions. She reported a persistent desire for weight loss, laxative abuse, and progressive weight loss over 4 years. Ten months before admission, her oral intake significantly declined, necessitating intravenous nutritional supplementation. Upon admission, the patient was in critical condition and largely unresponsive. Her history was obtained from her mother, who reported that, despite a diagnosis by the Mie University Psychiatry Department, the patient did not adequately follow treatment. Repeated attempts to secure care were unsuccessful, as hospitals refused treatment due to her psychiatric condition. This lack of sustained medical intervention contributed to her severe malnutrition, ultimately resulting in her emergency admission.

Upon admission to the Internal Medicine Department of our hospital, the patient presented with significant physical parameters indicative of severe malnutrition. She measured 155 cm in height, weighed 22.8 kg, and exhibited a remarkably low BMI of 9.5 kg/m2. Additionally, her neurological status was assessed using the Glasgow Coma Scale, revealing a score of E3V5M6. There was confusion due to debilitation, but no paralysis in the limbs (although there was muscle weakness), and no pathological reflexes were observed. Hemodynamically, she presented with hypotension, with a blood pressure reading of 74/42 mm Hg and a bradycardic pulse rate of 47 beats per min. Her body temperature was notably low at 35.1°C, yet her percutaneous oxygen saturation remained within normal limits at 100%. Laboratory investigations unveiled leukocytosis (23500/μL) with neutrophilia (86.8%), indicative of systemic inflammation.

Furthermore, liver dysfunction (AST 1104 IU/L; 10–35, ALT 424 IU/L; 10–35) with hypoproteinemia (6.0g/dL), hypoalbuminemia (3.9g/dL), hypogammaglobulinemia (IgG 617 IU/mL), and severe renal impairment (BUN 191.7 mg/dL; 9.0–22.0, creatinine 2.26 mg/dL; 0.40–0.90, eGFR 22.1 mL/min; >60) with marked dehydration were evident. Electrolyte analyses revealed derangements, including hyponatremia (Na 123 mEq/L), hypocalcemia (Ca 6.2 mg/dL), hyperphosphatemia (P 16.1 mg/dL), and hypermagnesemia (Mg 3.6 mg/dL) (Table 1). Endocrine assessments revealed hypothyroidism, with elevated levels of thyroid-stimulating hormone (11.0510 uIU/mL) and suppressed free T3 (0.850 pg/mL) and free T4 (0.860 ng/mL) levels. Notably, there were elevations in adrenocorticotropic hormone (69.6 pg/mL), cortisol (397 μg/dL), and aldosterone (3700 pg/mL) levels, suggesting dysregulation of the hypothalamic-pituitary-adrenal axis.

Upon admission, the patient presented with dehydration and renal failure, managed initially with a 5% dextrose solution and type 1 fluid (1300–1600 mL/day). Potassium was avoided to mitigate hyperkalemia risk associated with renal failure. Central venous nutrition and amino acid solutions were introduced to support nutritional needs, while oral liquid in-take was cautiously increased from 300 kcal/day on day 2 to 700 kcal/day by day 16 to prevent refeeding syndrome. By day 8, prednisolone (10 mg/day) was initiated to treat autoimmune thrombocytopenia. By day 14 of hospitalization, the patient developed symptoms including fever, dyspnea, lower limb edema, and ascites. Chest X-ray and computed tomography (CT) imaging revealed extensive bilateral pleural effusions, which were not noted upon admission (Figure 1A–1C). A needle thoracocentesis was performed, and fluid aspirated from the left pleural cavity appeared purulent, showing a predominance of neutrophils and elevated adenosine deaminase levels. Polymerase chain reaction and T-SPOT TB tests for Mycobacterium tuberculosis were negative. Bacterial cultures identified Providencia rettgeri and group G Streptococcus from the left pleural fluid, while the right pleural effusion culture was negative. Concurrent blood tests revealed elevated C-reactive protein (11.417 mg/dL) and significant hypoproteinemia (total protein 3.7 g/dL, albumin 1.2 g/dL), with normalized leukocyte counts (6000/μL). These findings led to a diagnosis of empyema thoracis caused by a mixed infection of Providencia rettgeri and group G Streptococcus.

Treatment was initiated with intravenous meropenem (1.0 g twice daily), considering the susceptibility profiles of both pathogens. Despite this, the patient’s clinical condition showed no improvement, necessitating additional intervention. On day 18, a double-lumen trocar was inserted into the left thoracic cavity for continuous drainage and saline flushing of the pleural fluid. Following this procedure, the patient’s fever subsided by day 21, and the thoracic intubation tube was removed on day 26. However, the fever recurred on day 48, and a follow-up CT scan confirmed persistent empyema thoracis. Intravenous ceftriaxone (2 g/day) was subsequently administered. On day 52, a 12 Fr aspiration catheter was reintroduced into the left thoracic cavity for continuous suctioning. The bacterial cultures from the aspirated fluid again identified Providencia rettgeri and group G Streptococcus, confirming the persistence of the initial pathogens. Further chest CT imaging on day 65 indicated a significant reduction in pleural effusion, compared with the earlier stages (Figure 1D). The patient’s condition continued to improve, and the aspiration catheter was removed on day 72 of hospitalization. Ceftriaxone or meropenem was continued until day 82 to ensure the infection was fully controlled. A follow-up chest radiograph obtained on day 79 demonstrated a near-complete resolution of bilateral pleural effusion (Figure 1E). By the end of the treatment period, the patient exhibited significant clinical improvement, with all signs of empyema and infection resolving.

Consent considerations were carefully addressed in managing this patient’s treatment, although they varied by intervention due to the patient’s condition. For the administration of intravenous fluids, no formal written consent was obtained from the patient, reflecting the emergent nature of her hydration needs. The patient explicitly refused enteral nutrition, and therefore it was not administered. In contrast, for central venous nutrition, which is a more invasive procedure, written consent was indeed secured. However, due to the patient’s debilitated state, she was unable to sign the consent document herself, and it was obtained from her mother instead. This approach ensured ethical compliance while addressing the patient’s critical nutritional requirements and medical needs, acknowledging her limited capacity to consent due to her health status.

Discussion

AN is a severe and potentially life-threatening eating disorder characterized by extreme food restriction, intense fear of weight gain, and distorted body image perceptions [1]. AN incidence is approximately 8 per 100 000 persons annually [6]. Compared with other psychiatric conditions, AN carries a notably high mortality rate, with causes of death, including emaciation from prolonged starvation, arrhythmias, electrolyte imbalances, suicide, infections, and refeeding syndrome [7].

In the case presented, the patient exhibited severe weight loss equivalent to −56.9% of standard body weight, abnormal eating behaviors, distorted body image perceptions, onset before the age of 30 years, amenorrhea, and absence of organic diseases as a cause of weight loss. Upon admission, precautions were taken to prevent refeeding syndrome associated with nutritional therapy initiation. Although increased infusion volumes led to peripheral edema, refeeding syndrome was successfully avoided. However, thrombocytopenia of unknown etiology with nasal bleeding occurred during the disease course, a manifestation observed in approximately 10% of patients with AN [8]. In the absence of disseminated intravascular coagulation findings, prednisolone was administered for 7 days, improving thrombocytopenia. Nonetheless, empyema thoracis subsequently developed, possibly linked to corticosteroid use, which is known to increase infection risk [9].

Empyema thoracis, a severe pleural cavity inflammation caused by pathogenic microorganisms, results in pus accumulation [10]. Common causative bacteria include Staphylococcus aureus, Streptococcus pneumoniae, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Escherichia coli [10]. Immunocompromised individuals, such as those receiving steroids, are at higher risk of empyema thoracis [11]. Starvation and malnutrition in AN weaken respiratory muscles, which are crucial for breathing and sputum clearance. These conditions also impair hemato-logical, immune, and cellular functions. Gelatinous bone marrow transformation in AN often leads to leukopenia [8]. Despite leukocytosis attributed to dehydration upon admission, white blood cell counts remained within normal limits despite markedly elevated C-reactive protein values during empyema thoracis onset. Studies indicate that patients with AN exhibit decreased peripheral blood polymorphonuclear bactericidal capacity and adherence, rendering them more susceptible to infections [12]. Additionally, alterations in lymphocyte subsets in AN patients, such as decreased CD8+ and natural killer cell counts and elevated CD4/CD8 ratios, increase infection susceptibility [13]. Furthermore, severe malnutrition in AN is associated with reduced serum IgG and IgM levels, contributing to susceptibility to infectious diseases [14].

Providencia rettgeri, an opportunistic pathogen known for causing various infections, including traveler’s diarrhea and urinary tract infections, was identified in this case [4]. Providencia rettgeri exhibits intrinsic resistance to many antibiotics and possesses robust biofilm-forming capabilities, rendering treatment challenging [15,16]. Co-infection with group G Streptococcus likely exacerbated empyema thoracis. Although both bacterial species were sensitive to meropenem in vitro, antibiotic therapy alone failed to resolve empyema thoracis, necessitating pleural drainage. Biofilm formation, inadequate antibiotic concentrations, and compromised immunity likely contributed to treatment failure. The transmission route remains uncertain, with possible mechanisms including upper respiratory tract infection via aspiration or bacterial translocation from the intestine due to gastrointestinal mucosal alterations. It is important to acknowledge here that standard pleural drainage techniques, particularly the use of wide-bore pleural catheters (28 Fr – 32 Fr), are a cornerstone in the management of empyema thoracis. These methods could have potentially mitigated the recurrence and reduced the length of the patient’s hospital stay. However, in this particular case, the decision to use alternative drainage methods was based on the patient’s unique clinical presentation and the multidisciplinary team’s assessment. Given the severe malnutrition, immunocompromised state, and the patient’s overall frailty, the team opted for a less invasive approach, balancing the need for effective drainage with the patient’s specific vulnerabilities. This case underscores the complex clinical decisions required in managing critically ill patients with AN, where standard interventions must be carefully adapted to the individual’s condition.

The immunodeficiencies in AN extend beyond the general malnutrition-related immune suppression, presenting unique vulnerabilities that significantly elevate the risk of opportunistic infections. Specifically, the profound and chronic nutritional deficits in AN disrupt the cellular and humoral immunity and the integrity of the mucosal barriers, which is critical in defending against unusual pathogens such as Providencia rettgeri and group G Streptococcus. These pathogens are typically opportunistic, exploiting the compromised immune defenses in patients with severe malnutrition and immune dysregulation. Furthermore, the use of steroids in this context acts as a double-edged sword. While potentially beneficial in managing certain acute complications, steroids can further suppress the immune response, exacerbating the risk of infections in an already vulnerable patient. This compound effect underscores the necessity for a cautious and judicious use of immunosuppressive therapies in patients with AN, particularly those with active infections. Consequently, managing infections in AN requires tailored strategies that address the immediate infectious process and the underlying malnutrition and immune dysfunction. A multidisciplinary approach involving nutritionists, endocrinologists, immunologists, and infectious disease specialists is essential to enhance outcomes. This collaborative effort ensures comprehensive management that addresses the complex interplay of nutritional recovery, immune restoration, and targeted treatment of infections, ultimately aiming to stabilize and improve the patient’s overall health status.

In treating the patient’s empyema thoracis, an initial choice was to use meropenem, a broad-spectrum antibiotic, considering the severity of the infection. Typically, combinations such as ceftriaxone plus clindamycin, sulbactam plus ampicillin, or cefepime plus clindamycin might be used, especially if infections by organisms like Pseudomonas are suspected. However, due to the complexity and severity of the infection in this case, meropenem was selected for its extensive antibacterial coverage. Upon diagnosing the empyema thoracis, antibiotic therapy and pleural drainage were deemed necessary. There was a delay in treatment initiation, as chest X-rays and subsequent drainage were not performed immediately after the onset of symptoms but only confirmed later. It was discovered that the effusions in the lungs were exudative in the left lung and transudative in the right, leading to drainage being performed only on the left side. Cultures taken during treatment showed sensitivity to both the meropenem and ceftriaxone, which confirmed the appropriateness of the initial antibiotic choice. Thus, no changes were made to the antibiotic regimen based on these sensitivities. This approach aimed to manage the infection effectively while minimizing adjustments, unless necessitated by culture results.

Conclusions

In summary, we present a unique case of empyema thoracis caused by Providencia rettgeri and group G Streptococcus in a young woman with AN. Awareness of opportunistic infections in a patient with AN, especially following corticosteroid use, is crucial for timely intervention and improved outcomes.