Hrev_master Abstract Urinary Tract Infections (UTIs) are among the most common infections in individuals with Diabetes Mellitus (DM) and can progress to severe complications. This case report presents a 38- year-old male with poorly controlled DM who developed Escherichia coli pyelonephritis complicated by bacteremia and subsequent bacterial meningitis. Despite initial antibiotic therapy for a complicated UTI, the patient developed neurological symp- toms, including confusion, drowsiness, and clinically evident nuchal rigidity. Laboratory findings supported bacterial meningi- tis, though Cerebrospinal Fluid (CSF) cultures remained sterile, likely due to prior antibiotic administration. Blood and urine cul- tures confirmed E. coli as the causative pathogen. Management included broad-spectrum antibiotics, corticosteroids, insulin, and the placement of a double-J stent. The patient gradually improved and was discharged after two weeks with full recovery. This case underscores the rare but life-threatening progression of pyelonephritis to meningitis in diabetic patients. Clinicians should maintain a high index of suspicion for systemic infections in dia- betics presenting with UTIs and neurological symptoms, as early diagnosis and aggressive management are critical for reducing morbidity and mortality. Introduction Urinary Tract Infections (UTIs) ranked as the second most common infection among individuals with diabetes, following lower respiratory tract infections, with incidence rates of 51.4 per 1,000 years for men and 147.9 per 1,000 years for women.1 In hos- pitalized individuals diagnosed with acute pyelonephritis, Diabetes Mellitus (DM) has been identified as the predominant predisposing factor.2 Furthermore, the severity of UTIs is exacerbated in patients with DM; the average hospitalization rate for those with acute pyelonephritis is notably higher among diabetics compared to their nondiabetic counterparts.3 In individuals with DM, pyelonephritis often presents bilaterally and is associated with a higher risk of complications.4 The immunocompromised state in diabetics can Emergency Care Journal 2025; volume 21:13700 [Emergency Care Journal 2025; 21:13700] [page 59] From bacterial pyelonephritis to meningitis: a case report and literature review Asif Dabeer Jafri,1 Om Prakash Sanjeev,2 Shyam Sundar,2 Kayenaat Rizvi3 1Department of Emergency Medicine and Tele-ICU Service, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh; 2Department of Emergency Medicine, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh; 3Department of Community and Forensic Medicine, ERA’s Lucknow Medical College and Hospital, Lucknow, Uttar Pradesh, India Correspondence: Asif Dabeer Jafri, Department of Emergency Medicine and Tele-ICU Service, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India. E-mail: Asif_jafri2003@yahoo.co.in Key words: Escherichia coli, urinary tract infection, pyelonephritis, meningitis, diabetes mellitus Funding: none. Conflict of interest: we declare that we do not have any conflict of interest. Ethics approval and consent to participate: no ethical committee approval was required for this case report by the Department, because this article does not contain any studies with human partic- ipants or animals. Informed consent was obtained from the patient included in this study. Patient consent for publication: the patient gave his written consent to use his personal data for the publication of this case report and any accompanying images. Availability of data and materials: all data underlying the findings are fully available. Received: 4 February 2025. Accepted: 31 March 2025. Early view: 28 April 2025. This work is licensed under a Creative Commons Attribution 4.0 License (by-nc 4.0). ©Copyright: the Author(s), 2025 Licensee PAGEPress, Italy Emergency Care Journal 2025; 21:13700 doi:10.4081/ecj.2025.13700 Publisher's note: all claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher. Highlights - Diabetics & UTIs: diabetic patients are at higher risk for severe UTIs, which can progress to life-threatening infections. - Rare complication: this case highlights the unusual progression of pyelonephritis to E. coli meningitis in an adult. - Diagnostic challenge: sterile CSF cultures may occur due to prior antibiotics, complicating diagnosis. - Urgent management: early recognition and aggressive treatment, including antibiotics and urological intervention, are crucial. - Clinical implication: neurological symptoms in diabetic UTI patients should raise suspicion for meningitis to prevent severe outcomes. mask typical signs and symptoms, leading to delayed diagnosis and treatment, which may result in severe infections and increased mor- tality. Local complications of pyelonephritis in diabetic patients include Emphysematous Pyelonephritis (EPN), perirenal and pararenal abscesses. Progression to meningitis is rare. This article explores a case of acute bacterial meningitis, which is an uncom- mon complication arising from pyelonephritis. The patient present- ed to the Emergency Department with symptoms indicative of a uri- nary tract infection. Within 12 hours, the patient’s condition deteri- orated, leading to drowsiness and confusion. Neurological exami- nation revealed signs consistent with meningeal irritation, prompt- ing the need for cerebrospinal fluid analysis. The treatment protocol involved the immediate administration of antibiotics, corticos- teroids, and supportive care. Meningitis caused by E. coli is associ- ated with a significant mortality rate if not swiftly identified, under- scoring the importance of early detection and appropriate manage- ment for the diagnosis and treatment of this serious condition. Case Report A 38-year-old male patient arrived at our hospital with a two- day history of fever and non-radiating back pain, accompanied by dysuria that had persisted for five days. Despite taking analgesics obtained from a local pharmacy, his fever and pain did not improve. The patient had a history of diabetes for the past ten years, which was poorly controlled due to non-compliance with drugs. Considering his diabetic condition and urinary tract infec- tion, a provisional diagnosis of complicated urinary tract infection was established, and he was initiated on intravenous antibiotics. However, twelve hours after admission, he became drowsy, con- fused, and disoriented regarding time and place, along with symp- toms of headache and vomiting, prompting the addition of urosep- sis and meningitis to our differential diagnosis. Upon admission, the patient was agitated and febrile, with a temperature of 39.6°C. His vital signs at the time of admission were recorded as follows: a pulse rate of 121 beats per minute, a respiratory rate of 24 breaths per minute, blood pressure of 100/60 mmHg, and an oxygen saturation level of 94% while breathing room air. Upon examination of the abdomen, tenderness was noted upon palpation, and no organomegaly was detected. The neurolog- ical evaluation showed no significant abnormalities except for nuchal rigidity. All cranial nerves were found to be intact. The patient was swiftly started on broad-spectrum intravenous antibiotics, corticosteroids, insulin, and antipyretics. Blood and urine cultures were collected at the time of admission before the administration of antibiotics; however, the report was received after 72 hours. Laboratory parameters at admission and on the day of discharge are presented in Table 1. A Non-Contrast Computed Tomography (NCCT) scan of the head and an NCCT scan of the abdomen were recommended. The NCCT scan of the abdomen showed an enlarged left kidney along with fat stranding suggestive of pyelonephritis, as demonstrated in Figure 1, while the NCCT scan of the head showed no abnormalities. A lumbar puncture was performed and the Cerebrospinal Fluid (CSF) examination revealed a cloudy and turbid appearance. The protein concentra- tion was markedly elevated at 284 mg/dl, significantly exceeding Mini review [page 60] [Emergency Care Journal 2025; 21:13700] Table 1. Laboratory parameters at the time of admission and upon discharge. Analyte (Reference range) At admission At discharge Hb (13-17 g/dL) 11.2 10.6 TLC (4-11 × 109/L) 21,000 7,200 TPC (150-400 × 109/L) 120,000 210,000 S. Na (135-145 mEq/L) 134 141 S. K (3.5-5 mEq/L) 3.9 4.4 S. Cl ( 96-115 mEq/L) 95 108 SGOT (5-40 U/L) 45 32 SGPT (5-40 U/L) 60 25 T. Bilirubin (0.0-2.0 mg/dL) 0.9 0.6 Alkaline Phosphatase (40-129 IU/L) 180 210 Total Protein ( 6.0-8.3 g/dL) 6.1 6.4 Serum Albumin (3.3-5.2 g/dL) 3.1 3.3 Blood Urea (13-45 mg/dL) 120 40 Serum Creatinine (0.5-1.5 mg/dL) 2.2 1.0 Serum Calcium (8.6-10.3 mg/dL) 8.2 9.0 TSH (0.45-5.0 mIU/L) 1.3 1.3 HbA1c ( <5.7%) 10.5 10.5 Procalcitonin (<0.05 mcg/L) 16 0.01 CRP 0.00-1.00 mg/dL) 60 2 Urine Routine Examination (Urine R/E) WBCs (2-5/HPF) 18 3 Urine Sugar (0-15 mg/dL) 210 20 Urine Protein (<10 mg/dL) 170 30 Hb, Hemoglobin; TLC, Total Leukocyte Count; TPC, Total Platelet Count; S. Na, Serum Sodium; S. K, Serum Potassium; S. Cl, Serum Chloride; SGOT, Serum Glutamic-Oxaloacetic Transaminase; SGPT, Serum Glutamic- Pyruvic Transaminase; TSH, Thyroid-Stimulating Hormone; HbA1c-Glycated Hemoglobin; CRP, C-Reactive Protein; Urine R/E, Urine Routine Examination; WBCs, White Blood Cells. the normal range of 15–45 mg/dL. Conversely, glucose levels were considerably low at 22 mg/dL, which is below the normal range of 50–80 mg/dL. Furthermore, the total cell count was recorded at 1700 cells/mm³, whereas the normal range is 0-5 cells/mm³, with neutrophils constituting 90% and lymphocytes 10% of the total cell count. Neutrophils are generally absent in normal CSF. These findings are suggestive of bacterial meningitis. The CSF culture yielded no growth. Urine and blood cultures showed the growth of E. coli, while the CSF cultures returned sterile results. The results of the tests conducted on the tropical panel, which encompassed malaria, scrub typhus, salmonella, leptospirae, dengue, and the viral panel, were negative. Additionally, the chest X-ray revealed no abnormalities. Initially, the patient received Intravenous (IV) ceftriaxone at a dosage of 2 grams administered twice daily, in conjunction with IV fluids and subcutaneous insulin adjusted according to a sliding scale. To address fever and pain, IV paracetamol was also provided at a dosage of 1 gram three times daily. As the patient’s condition worsened, displaying symptoms indicative of meningitis, the treat- ment regimen was modified to incorporate IV vancomycin at a dosage of 1 gram twice daily and IV dexamethasone at 4 grams thrice daily. However, after a period of 72 hours without any notable improvement in the patient’s condition, and following pos- itive findings from urine and blood cultures, the IV ceftriaxone was replaced with a higher dosage of IV meropenem at 2 grams administered three times daily. In light of pyelonephritis being identified as the source of infection, consultations with Urology were sought, and the patient was recommended for the placement of a double-J stent. Following the treatment provided, the patient showed gradual improvement, achieving hemodynamic stability and becoming afebrile. All laboratory parameters returned to nor- mal, and he was successfully discharged after a two-week hospital stay, with a complete restoration of sensorium, being alert and well-oriented. Discussion Acute pyelonephritis is primarily caused by microorganisms that ascend from the urethra through the bladder into the upper uri- nary tract. In rare instances, the kidneys may become infected through the bloodstream. This condition poses a greater risk for individuals with diabetes, as it often presents without pain, leading to potential oversight. In diabetic patients, acute pyelonephritis is more likely to be complicated by conditions such as pyonephritis or papillary necrosis, both of which can jeopardize the patient’s life or renal function. Additionally, the diabetic kidney is susceptible to a specific form of glomerulopathy characterized by nephroan- giosclerosis and interstitial damage, making it imperative that all infections are treated aggressively to prevent further complica- tions. Acute pyelonephritis is diagnosed when a patient exhibits symptoms such as fever, nausea, vomiting, pain abdomen, dysuria, and hematuria. Ultrasound imaging studies are performed, and findings indicative of pyelonephritis include a combination of an enlarged kidney, the presence of fluid collections, and/or per- inephric stranding. The primary causative agent of pyelonephritis is Escherichia coli, which is identified in 40–90% of affected indi- viduals. Other frequently implicated organisms include Proteus mirabilis, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Enterococcus species. Meningitis caused by E. coli in adults represents a serious medical condition, frequently associated with unfavorable out- comes and a high mortality rate, even when appropriate antimicro- bial therapy is administered. In contrast to the general population suffering from bacterial meningitis caused by other pathogens, patients with Gram-negative bacilli meningitis, such as E. coli, tend to present with a higher prevalence of comorbidities.5 Escherichia coli is an uncommon etiological agent of community- acquired meningitis in adults, accounting for approximately 1% of Mini review Figure 1. The CT scan reveals an enlarged left kidney exhibiting heterogeneous attenuation, along with perinephric fat stranding, as indi- cated by the blue arrow in the frontal (a) and axial (b) views. [Emergency Care Journal 2025; 21:13700] [page 61] all meningitis cases. It typically arises in individuals with predis- posing risk factors, including diabetes mellitus, alcoholism, cirrho- sis, HIV infection, and various malignancies.6 The occurrence of E. coli meningitis is generally secondary to an infection located either at a distant site or nearby, such as infections of the urinary tract or gastrointestinal system.7-9 Emphysematous Pyelonephritis (EPN) is a severe and poten- tially fatal kidney infection marked by the presence of gas within the renal tissue, collecting system, or perinephric area.10 This uncommon yet dangerous condition is predominantly caused by poorly controlled blood glucose levels and obstructions in the uri- nary tract. The prevalence of diabetes in patients diagnosed with EPN ranges from 50% to 90%, making it the most significant risk factor associated with this condition. Treatment options may con- sist of antibiotic therapy alone, percutaneous drainage combined with antibiotics, or nephrectomy in cases where the disease is advancing or the patient exhibits unstable hemodynamics. The pri- mary pathogen identified in urine and blood cultures is Escherichia coli.11 Cromlin et al. documented a case involving O117:K52:H E. coli meningitis accompanied by multiple brain abscesses, identifying acute pyelonephritis as the primary source of infection.12 Gram-Negative Bacilli (GNB) represent a rare etiol- ogy of bacterial meningitis, with global incidence rates varying from 0.7% to 7%. Escherichia coli, a commensal organism found in the human gastrointestinal tract, is the predominant pathogen responsible for Urinary Tract Infections (UTIs). Additional clinical presentations associated with GNB include nosocomial pneumo- nia, cholecystitis, peritonitis, cellulitis, osteomyelitis, and septic arthritis.13,14 The occurrence of multi-organ dysfunction diminishes the likelihood of recovery.15 In patients with spontaneous bacterial meningitis, factors such as advanced age (≥65 years), positive blood cultures, inappropriate initial antibiotic therapy, and the presence of neurological and systemic complications—including shock, coagulation disorders, and acute renal failure—were linked to an increased risk of mortality.16 The mortality rate linked to community-acquired E. coli meningitis is significantly high, rang- ing from 50% to 90%, and may reach as much as 100% in individ- uals suffering from liver cirrhosis.17 The optimal management of Emphysematous Pyelonephritis (EPN) remains a topic of ongoing debate, particularly regarding the appropriate timing for surgical intervention. Nonetheless, sim- ilar to the management of all forms of pyelonephritis, it necessi- tates fluid and electrolyte resuscitation, administration of antibi- otics, glycemic control, and, when indicated, alleviation of any obstruction. In cases where there is clinical deterioration within 48 hours or a lack of improvement, it may be advisable to either per- sist with medical management in conjunction with Percutaneous Drainage (PCD) or consider surgical nephrectomy.18-20 The situation we encountered led to the conclusion that the underlying condition was pyelonephritis due to Escherichia coli infection, which progressed to bacteremia and subsequently seed- ed into the central nervous system, causing meningitis. While E. coli was not detected in the Cerebrospinal Fluid (CSF), this absence can likely be attributed to the administration of antibiotics before the CSF was collected. Nonetheless, the patient exhibited clear signs of acute bacterial meningitis, as supported by the find- ings from the CSF analyses and the positive clinical findings. The scenario underscores the necessity of recognizing that severe infections may affect distant organs, including the central nervous system, particularly in individuals with compromised immune systems who are susceptible to rapid deterioration from the dissemination of infection originating from an initial site, such as a urinary tract infection in this instance. Therefore, it is crucial for healthcare professionals operating in emergency settings to maintain a heightened awareness of these potential complications to avoid diagnostic delays and mitigate the risk of mortality. Conclusions Meningitis should always be considered as a potential differen- tial diagnosis in patients presenting with signs of infection at a dis- tant site, such as a urinary tract infection, especially when these symptoms are accompanied by fever and changes in mental status. Early diagnosis can significantly improve patient outcomes. References 1. McDonald HI, Nitsch D, Millett ER, et al. New estimates of the burden of acute community-acquired infections among older people with diabetes mellitus: A retrospective cohort study using linked electronic health records. Diabet Med 2014;31:606–14. 2. Chiu PF, Huang CH, Liou HH, et al. Long-term renal out- comes of episodic urinary tract infection in diabetic patients. J Diabetes Complications 2013;27:41–3. 3. Nitzan O, Elias M, Chazan B, Saliba W. Urinary tract infec- tions in patients with type 2 diabetes mellitus: review of preva- lence, diagnosis, and management. Diabetes Metab Syndr Obes 2015;8:129-36. 4. 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