Unique Presentation of Asymptomatic Bacteriuria, Vertebral Osteomyelitis, and Iliopsoas Abscess Due to in a 73-Year-Old Man with Type 2 Diabetes Mellitus on Empagliflozin

Introduction

Vertebral osteomyelitis is a rare condition with a reported incidence of 4.8 per 100 000 hospitalizations per year in the United States between 1998 and 2013 [1]. Patients presenting with vertebral osteomyelitis typically have underlying risk factors, including prior spinal surgery, diabetes mellitus, infective endocarditis, injection drug use, and other immunocompromised states [2].

The leading cause of vertebral osteomyelitis is Staphylococcus aureus [3]. Gram-negative rods are a less common etiology and are typically caused by urinary tract infection [3].

SGLT2 inhibitors block reabsorption of filtered glucose by inhibiting SGLT2 found in the proximal tubules of the kidneys, ultimately lowering serum glucose levels in DM patients [4].

Patients with DM can be managed with single therapy with SGLT2 inhibitors or in combination [4]. Standard of Medical Care in Diabetes recommends dual therapy of SGLT2 inhibitor and metformin in treatment of DM patients with hemoglobin A1c greater than 9% [4]. Empagliflozin is used in diabetic patients in treating hyperglycemia and is also used in heart failure management. It has been shown that empagliflozin reduces the risk of cardiovascular death in adults with DM and cardiovascular disease [4]. Additionally, empagliflozin reduces hospitalizations for heart failure and death from cardiovascular causes [4].

SGLT2 inhibitors can cause a gamut of adverse effects, including hypotension, renal injury, hyperlipidemia, urinary tract infection, Fournier’s gangrene, and pyelonephritis [4]. A systematic review and meta-analysis performed by Nani et al demonstrated SGLT2 inhibitors increase the risk of ulcers of the lower limbs, amputations, and overall infections; however, there was no association of SGLT2 inhibitors with lower-limb osteomyelitis, fractures, peripheral arterial disease, or symmetric polyneuropathy [5].

Asymptomatic bacteriuria is defined as the presence of bacteria in an adequately collected urine sample of a patient without any symptoms or signs of urinary tract infection [6]. Incidence of asymptomatic bacteriuria increases with age, with an incidence of 15% or greater in men and women aged 65–80 years [6].

A few case reports showed patients with uncontrolled diabetes mellitus with Klebsiella pneumonia causing vertebral osteomyelitis and iliopsoas abscesses [7,8].

Herein, we report a case of a 73-year-old man with type 2 DM on empagliflozin who presented with back pain, found to have asymptomatic bacteriuria, lumbar vertebral osteomyelitis, and left iliopsoas abscess due to Klebsiella pneumoniae.

Case Report

Our patient was a 73-year-old man with a past medical history of ischemic heart disease, hypertension, diabetes mellitus, dyslipidemia, benign prostatic hyperplasia, and spinal stenosis with chronic lower back pain. His medications include aspirin 81 mg daily, lisinopril 20 mg daily, doxazosin 4 mg daily, atorvastatin 80 mg daily, metformin 1000 mg twice daily, and empagliflozin 25 mg daily. Empagliflozin 10 mg was initiated 4 months prior to admission, and the dose was increased to 25 mg daily after 2 months for better control of DM due to elevated hemoglobin A1c of 8%.

The patient presented to the emergency department (ED) due to severe lower back pain of 1-month duration. The pain was described as 8 out 10 in severity, radiating from the left flank to the left knee and was exacerbated with movement. He denied subjective fever, night sweats, dysuria, polyuria, urinary urgency, and urinary or fecal incontinence. He additionally denied a history of recurrent urinary tract infections, recent dental or urogynecologic procedures, new sexual partners, or history of injection drug use. The patient’s symptoms were insidious and progressively worsened over 1 month to the point that he could no longer stand up. During this period, he had 2 visits to the ED and both times he was discharged with painkillers. On his second visit to the ED, a spinal computed tomography (CT) scan showed spinal stenosis at the L4-L5 levels without any changes from previous imaging.

On admission, the patient’s vital signs were found to be in normal limits. Upon examination, there was no local tenderness to spinal palpation. Motor strength testing showed 4/5 on hip flexion and extension and other joints’ power was 5/5. Bilateral patellar and Achilles reflexes were graded 2 plus, bilateral Babinski sign was negative, and bilateral lower-extremity sensation was normal and symmetric. Both perianal sensation and anal sphincter tone were normal. Physical exam findings were normal, including auscultation of the heart.

His complete blood count revealed normal leukocytes count of 9800/uL (normal range: 4400–11 000/uL), with neutrophil percentage elevated at 85.4%. C-reactive protein (CRP) was elevated at 52.4 mg/L (normal range 0.0–8.0 mg/L), creatinine 0.8 mg/dL (normal range 0.6–1.2 mg/dL), and hemoglobin A1c 7.4%. Urinalysis showed 250 leukocytes per high-power field, nitrates +2 mg/dl, and few bacteria. Blood and urine cultures were taken. A lumbar spine CT scan showed discitisosteomyelitis at the L3-L4 levels with left iliopsoas abscesses (Figures 1, 2). Magnetic resonance imaging (MRI) of the lumbar spine revealed the same picture: signs of discitis-osteomyelitis at the L3-L4 levels with left iliopsoas abscesses (Figures 2, 3).

The patient was admitted to the internal medicine department and empiric treatment with ceftriaxone, and vancomycin was initiated; ceftriaxone dose was 2 grams daily, vancomycin loading dose was 25 mg/kg followed by 20 mg/kg twice daily. By the third day of admission, percutaneous biopsy of L4 was done and the iliopsoas abscess was drained under CT guidance with removal of 30 ml of purulent fluid (Figures 4, 5). The bone tissue and the purulent fluid were sent for cultures.

Urine culture showed growth of extended-spectrum beta-lactamase (ESBL) Klebsiella pneumoniae (Figure 6); therefore, the treatment was escalated to meropenem 1000 mg 3 times daily, and the susceptibility results are shown in Table 1. Blood culture revealed growth of ESBL Klebsiella pneumoniae (Figure 7), with the same antibiotic susceptibility seen in urine culture (Table 1). After 2 days, the bone tissue culture and the drained abscess culture showed growth of ESBL Klebsiella pneumoniae, with the same antibiotic susceptibility seen in both the urine and blood cultures (Table 1).

This finding raised the suspicion that the source of discitis and iliopsoas abscess was the urine. Therefore, multilocus sequence typing (MLST) was done to detect the genetic relationships between the 4 isolates (the Klebsiella pneumoniae from the urine, the blood, the bone tissue, and the drained iliopsoas abscess). It showed that the 4 isolates were from the same strain, and the sequence type (ST) of this strain was ST35 classical Klebsiella pneumoniae. Polymerase chain reaction (PCR) showed that all isolates carried genes encoding CTX-M-14 beta-lactamase; but SHV beta-lactamase, TEM beta-lactamase, and OXA beta-lactamase genes were not detected.

It is also important to note that the patient was on empagliflozin treatment, which can cause urinary tract infections. However, he denied any urinary symptoms; therefore, the source of infection was asymptomatic bacteriuria. This was a possible adverse effect of empagliflozin, with 4 points on Naranjo scale, and empagliflozin was discontinued.

Due to absence of improvement on physical examination and the up-trending CRP, an additional spinal CT was done, which showed no improvement of the discitis and the left iliopsoas abscess. As a result, on the 7th day of admission, he underwent another percutaneous drainage, with removal of 100 ml of purulent fluid, and a pigtail catheter was placed to allow further drainage. The drained abscess culture showed the growth of ESBL Klebsiella pneumoniae with the same antibiotic susceptibility seen in the previous cultures.

Under this treatment with physiotherapy, his condition began to improve and the CRP started to decline. He was treated as an inpatient with meropenem for 3 weeks and discharged to continue treatment at a rehabilitation center for another 3 weeks. He reported having significant improvement after 3 weeks at the rehabilitation center and he was able to walk and move without any back pain or discomfort.

Discussion

Here, we present a unique case presentation of a lumbar vertebral osteomyelitis-discitis and left iliopsoas abscess secondary to asymptomatic bacteriuria in a 73-year-old man with DM on empagliflozin who presented with back pain of 1-month duration. This case highlights the need for additional caution in elderly patients with DM on SGLT2 inhibitors presenting with back pain for possible vertebral osteomyelitis.

Vertebral osteomyelitis typically spreads hematogenously from distant sites, but it can also spread contiguously from adjacent soft tissue infection or may develop after surgical intervention or injection of the disc space [9]. Commonly, segmental arteries that supply the vertebrae bifurcate to provide blood to the neighboring bony segments, and the disease involves 2 adjacent vertebrae and the intervertebral disc; therefore, vertebral osteomyelitis and discitis may occur together, as seen in this case [9]. Vertebral osteomyelitis most commonly affects the lumbar spine (45%), then the thoracic spine (35%), followed by the cervical spine (20%) [9]. Iliopsoas abscesses are divided into primary, which may spread from a hematogenous or lymphatic source from a distant site, and secondary, which occur as a result of direct infection from an adjacent structure like skeletal, gastrointestinal, and urinary origin [10]. In a report of 124 cases of iliopsoas abscesses, vertebral osteomyelitis was the most common origin (35.5% of cases) [10].

The urinary tract was the most frequently presumed source of infection in 17% of cases, according to the systematic review of 1008 cases of pyogenic vertebral osteomyelitis [11]. In our case, the source of infection was most likely from asymptomatic bacteriuria, as the urine, the blood, the bone tissue,and the drained iliopsoas abscess cultures showed growth of the same organism with the same antibiotic susceptibility.

The leading bacterial pathogen causing vertebral osteomyelitis is Staphylococcus aureus, which accounts for more than 50% of cases in developed countries [3]. Gram-negative rods were identified in 7–33% of the patients with vertebral osteomyelitis, more frequently in patients with genitourinary tract infection, diabetes mellitus, older age, and compromised immune status [3]. E. coli is the most common gram-negative rod associated with pyogenic vertebral osteomyelitis [12]. In this case, Klebsiella pneumoniae was the causative agent, as it was isolated from the drained iliopsoas abscess, the blood, the bone tissue, and the urine cultures. Mylona et al reported that Klebsiella pneumoniae was the causative agent of 13 of 946 pyogenic vertebral osteomyelitis cases, accounting for 1.3% [11].

Back pain or neck pain are the most common symptoms of pyogenic vertebral osteomyelitis; it was reported in about 80% of the cases [3]. The pain is typically located in the infected disc space area and is worsened with physical activity or percussion to the affected area. It can remain for as long as several months before diagnosis [3]. Fever is common yet not necessarily always present. Neurological deficits are not as common; however, there is an elevated risk in patients with epidural abscesses, particularly in those with thoracic or cervical spine involvement [13]. If the infection spreads and causes an iliopsoas abscess, as in this case; the pain may radiate to the hip and the thigh [14]. Limitation of hip movement is common with iliopsoas abscesses, and the patient always avoids movements in which the iliopsoas muscle is stretched or extended [14].

The leukocyte count can be normal or elevated, and erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are elevated in more than 80% of cases [15]. Blood and urine cultures are positive in 50% of cases; therefore, they should be taken in patients presenting with possible vertebral osteomyelitis [12]. Plain radiographs are recommended in patients with suspected vertebral osteomyelitis [16]. However, plain radiographs are typically within normal limits at early stages of infection, and it may take 3 weeks or more after the initial stages of symptoms for early changes to be apparent [16]. Magnetic resonance imaging (MRI) is the best imaging to detect vertebral osteomyelitis with sensitivity, specificity, and accuracy of more than 90%. MRI is typically positive early in the course of the infection and provides the best details regarding location and changes in inflammation [16]. Computed tomography (CT) is the criterion standard to detect the presence of an iliopsoas abscess. CT-guided biopsy of vertebral osteomyelitis or CT-guided needle aspiration of iliopsoas abscess is essential to isolate the etiologic organism [14,17].

The optimal treatment of pyogenic vertebral osteomyelitis is antimicrobial therapy; however, some patients need surgical intervention [18]. If possible, antibiotics should be withheld until a microbial diagnosis is established. However, antibiotics should be started immediately in patients with sepsis, septic shock, hemodynamic instability, and progressive or severe neurological symptoms [18]. The indications for surgical debridement and/or spinal stabilization include the development of neurologic deficits or symptoms of spinal cord compression and evidence of progression or recurrence despite proper antimicrobial therapy [18]. Management of iliopsoas abscess consists of drainage and antimicrobial therapy. Percutaneous drainage (by ultrasound or CT guidance) is successful in 90% of cases [19,20].

In 2018, Yu et al described a 64-year-old woman with poorly controlled DM who presented with a fever of 2-day duration, and was found to have vertebral osteomyelitis at L2 level and bilateral psoas abscesses due to Klebsiella pneumoniae. She was managed with antibiotic therapy, bilateral CT-guided drainage of psoas abscesses, and minimally invasive spinal internal fixation, with good outcome [7]. In 2020, Di Stasi et al described a 41-year-old obese man with uncontrolled DM and chronic alcoholic hepatopathy, who presented with diabetic ketoacidosis, fever, and difficulty walking. His MRI showed emphysematous vertebral osteomyelitis at L4-L5 levels, and blood cultures showed growth of Klebsiella pneumoniae, most likely due to hematogenous spread of pulmonary infection in a patient with alcohol abuse. He was treated with ceftazidime and tigecycline, with complete resolution of his symptoms [8]. In the present case, we describe a 73-year-old man with controlled DM (hemoglobin A1c 7.4% on admission) on empagliflozin treatment, who presented with severe back pain of 1-month duration. He was found to have discitis-vertebral osteomyelitis at the L3-L4 levels with left iliopsoas abscess, and was managed with meropenem and CT-guided drainage, with good outcome. His urine, blood, bone tissue, and drained abscess cultures showed growth of Klebsiella pneumoniae from the same strain with the same antibiotic susceptibility; therefore, the source of infection was most likely the urine.

SGLT2 inhibitors, including empagliflozin, can increase the risk of urinary tract infections [21]. Uitrakul et al showed that patients on SGLT2 inhibitors had a 3.71 times higher urinary tract infection risk than patients on non-SGLT2 inhibitors, with no significant difference between empagliflozin and other SGLT2 inhibitors [21]. In this case, the patient had asymptomatic bacteriuria, which could be an adverse effect of empagliflozin. A systematic review and meta-analysis by Nani et al showed no significant association between SGLT2 inhibitors and the onset of osteomyelitis, peripheral arterial disease, lower-limb fractures, and symmetric polyneuropathy, but they increase the risk of lower-limb local ulcers, amputations, and overall infections [5].

In this case report, we describe a patient who developed lumbar vertebral osteomyelitis and iliopsoas abscess. The source of infection was asymptomatic bacteriuria because the urine, the blood, the bone tissue, and the drained iliopsoas abscess cultures showed growth of the same organism with the same sensitivity profile. His asymptomatic bacteriuria could be related to the use of SGLT2 inhibitors.

Conclusions

We report a case of an elderly patient with diabetes mellitus on empagliflozin presenting with vertebral osteomyelitis and iliopsoas abscess secondary to asymptomatic bacteriuria, possibly secondary to empagliflozin, whose use has been increasing dramatically in the last few years. This highlights the importance of the complications of DM and SGLT2 inhibitors’ adverse effects, especially the increased risk of infections, and can aid clinicians in expanding the differential and enabling them to reach an accurate diagnosis and provide appropriate management. Although vertebral osteomyelitis is a less common cause of back pain, physicians should keep it in the differential diagnosis whenever a patient’s back pain is chronic and associated with motor weakness. This case highlights the need for additional caution in elderly patients with DM on SGLT2 inhibitors presenting with chronic back pain for possible vertebral osteomyelitis.