Peer Reviewed

Case in Point

Considering Prediabetes as a Risk Factor for Infectious Complications Following Transrectal Prostate Biopsy

Nicole Peritz, OMS-IV,
Joy Ishii Zarandy, DO, FAAFP, DABFM
Volume 65 - Issue 9 - September 2025

Introduction. A 66-year-old man presented to the emergency department (ED) with sudden onset fever, chills, and profound malaise approximately 36 hours after undergoing an uncomplicated transrectal prostate biopsy (TRPBx). 

Case Description. The patient initially presented to his primary care physician (PCP) with progressively worsening nocturia. His prostate was enlarged, symmetric, and non-tender on digital rectal exam, and his prostate-specific antigen (PSA) showed an increase from 2.4 to 5.8 compared with the previous year. He was referred to urology, where a prostate magnetic resonance imaging (MRI) revealed several suspicious lesions reported as PI-RADS 4 score, suggesting high risk for clinically significant cancer. He was promptly scheduled for outpatient biopsy of the lesions via transrectal ultrasound guidance and local anesthesia. Preprocedural preparation included rectal cleansing enemas 12 hours prior to and at the time of biopsy, confirmation of a normal urinalysis, and betadine sterilization of the area. Standard sterile technique was used to retrieve a total of 12 biopsies. The patient received intravenous (IV) ceftriaxone and ciprofloxacin for routine antibiotic prophylaxis intraoperatively. He tolerated the procedure well and was discharged home that afternoon with a 3-day course of oral (PO) cefdinir.  

By the next evening, the patient’s condition declined rapidly as he developed fever, chills, weakness, body aches, and gross hematuria. He denied dysuria, chest pain, nausea, or headache. En route to the ED, he became disoriented and lethargic.  

The patient’s medical history was significant for prediabetes with a most recent HbA1c of 6.3, and previously stable benign prostatic hyperplasia (BPH). His only routine medication was aspirin 81mg PO daily. His surgical history was insignificant other than the TRPBx. His 67-year-old brother was recently diagnosed with prostate cancer stage 4, and his sister died at 66 years old from lung cancer. He ran twice a week for exercise, and denied tobacco, alcohol, and drug use. 

Physical examination. In the ED, the patient was febrile with a temperature of 38.4 °C (101.2 °F), tachycardic with a pulse of 109 beats per minute, and tachypneic with a respiration rate of 24. His BMI was within normal range. He was drowsy and oriented to person and time but not to place nor situation. Otherwise, the examination of his heart, lungs, and abdomen were unremarkable.  

Diagnostic tests. Initial laboratory tests upon presentation to the ED showed changes reflective of dehydration on comprehensive metabolic panel. Complete blood count, Troponin-I, and B-natriuretic peptide levels were within normal ranges. His urinalysis showed positive leukocytes, blood, glucose, and protein, and negative ketones, nitrite, and bilirubin. Urine culture and blood cultures were positive for pan-sensitive Escherichia coli (E. coli).  

Treatment and outcome. The patient’s condition quickly improved with prompt IV fluid resuscitation and empiric IV vancomycin and aztreonam in the ED. Urology switched regimen to IV meropenem, and he remained afebrile throughout the remainder of his 3-day hospitalization. He was discharged home in stable condition on cefuroxime 500 mg PO twice daily for 13 additional days. He maintained close outpatient follow up with both urology and his PCP and experienced no further complications.   

Pathology reports for 8 of 12 prostate biopsies confirmed the presence of adenocarcinoma, with Gleason scores ranging 3+3=6 to 3+4=7.  He was treated successfully with radiation therapy, and his PSA levels remained stable below normal ranges on routine monitoring. Incidentally, 5 years later, the patient was diagnosed with diabetes mellitus type 2 with a HbA1c of 6.5, which is managed with lifestyle modifications and metformin PO. 

Discussion. Prostate biopsy is considered the standard for diagnosing prostate cancer with more than two million biopsies performed in the United States and Europe each year, although it is not without its inherent risks.1 Despite best practices, infectious complications occur in up to 7% of cases; including urosepsis which is responsible for 0.3% to 3.1% of cases.2 To reduce risk of infection in low-risk patients, a single dose of fluoroquinolone or cephalosporin is often prescribed.2,3 Patients considered high-risk for TRPBx-related infectious complication include those with past or current urinary tract infection (UTI), in-dwelling catheter, recent antibiotic use, or diabetes mellitus (HbA1c ≥ 6.5).2,4,5 These patients may receive targeted antibiotic prophylaxis based on rectal swab culture, or may opt for a transperineal approach, which is associated with a lower rate of infection, but unlike the transrectal approach, is performed under general anesthesia.6,7,8,9

This case represents a patient who by current criteria was assumed to be relatively low-risk for TRPBx-related infectious complications, but postoperatively developed urosepsis despite appropriate infection prevention protocols. However, a retrospective review of the patient brings into question to what degree his borderline-diabetic HbA1c level of 6.3 may have contributed to his outcome. While extensive research exists to illustrate the negative impact of diabetes mellitus on immune function, there are fewer studies to evaluate how a prediabetic HbA1c value between 5.7 and 6.4 may also interfere with immune function. 

Multiple studies describe a difference in immune profile markers in patients with prediabetes compared with those with normal glucose tolerance. For example, C-reactive protein (CRP), a strong indicator of inflammation, is found at higher levels in patients with prediabetes, and at even higher levels in those with diabetes.10,11 Similarly, levels of the receptor antagonist for proinflammatory cytokine IL-1 (IL-1RA) are elevated in prediabetes.10 This is theorized to be a response to the increased IL-1 and associated inflammatory state in this patient population.10 Anti-inflammatory cytokine adiponectin has been measured at lower levels in patients with prediabetes and appears to be even further depleted in patients with diabetes in comparison to individuals with normal blood glucose levels.12 On a molecular level, one study suggests that certain microRNAs which are positively associated with inflammatory markers like TNF-alpha are upregulated in prediabetes and further upregulated in diabetes.13 Another study illustrates a relationship between elevated inflammatory markers like CRP and infectious complications following an invasive procedure.14 Collectively, these findings suggest an ongoing state of inflammation in patients with prediabetes, whereas extensive research demonstrates that inflammation disrupts normal cell and tissue function and can ultimately increase infection risk.11.15 

Another study finds that patients with prediabetes may be at a higher risk for developing bacterial infection due to suppressed levels of psoriasin, an antimicrobial peptide (AMP).16 Epithelial cells in the urinary tract express antimicrobial peptides like psoriasin, which help to limit growth of bacteria; psoriasin is considered the most potent AMP against E.coli.16 This patient population is also noted to have lower levels of occludin, a protein which helps to preserve the protective barrier function of the urinary tract epithelium.16  

Based on this research, it may be prudent to include patients with prediabetes in a higher risk category for postoperative infection. Further research is needed to determine the exact HbA1c level at which heightened precautions should be initiated, while also being mindful to minimize adverse outcomes associated with increasing infection prevention measures. Current guidelines for managing patients considered to be high-risk for TRPBx vary greatly between practices and are not well-defined.8 Interventions including pre-procedural rectal preparation using povidone-iodine or a transperineal approach have shown greater effectiveness at reducing infection rates relative to others.6 While the use of metformin is not currently considered when determining postoperative infection risk for a patient, studies suggest it may strengthen patient immunity against bacterial threats.17 One study demonstrates enhanced bactericidal activity against and clearance of intracellular and extracellular E. coli in uroepithelial cells treated with metformin compared with the control.17  Furthermore, metformin has been suggested to upregulate antimicrobial peptides LL-37 and RNase7, which help prevent bacterial infection in the urinary tract.17 While metformin is neither FDA approved for the prevention of diabetes nor infection, further research may be warranted to evaluate whether metformin has a protective effect against infection compared with patients with similarly elevated HbA1c levels who are not on metformin.  

Conclusion. While the impact of prediabetes on immune function and infection risk is not as well-established as with diabetes mellitus, research suggests immune markers and structural proteins involved in combating infection are proportionately altered in patients with chronic glucose intolerance. Future studies are needed to determine whether patients with prediabetes should be placed in a higher risk category for developing post-procedural infectious complications, such as with TRPBx. As such, it may be reasonable to consider extending current prophylactic strategies used for patients with diabetes to those with prediabetes at a certain HbA1c cutoff as well. Until then, these potential suggestions exist on speculation alone. 

AUTHORS: 
Nicole Peritz, OMS-IV; Joy Zarandy, DO, FAAFP 

AFFILIATIONS: 
1Medical Student, Philadelphia College of Osteopathic Medicine, Suwanee, GA 
2Department of Family Medicine, Philadelphia College of Osteopathic Medicine, Suwanee, GA 

CITATION:
Peritz N, Zarandy J. Considering prediabetes as a risk factor for infectious complications following transrectal prostate biopsy. Consultant. Published online May 22, 2025. doi:10.25270/con.2025.05.000005

DISCLOSURES: 
The authors report no relevant financial relationships. 

DISCLAIMER: 
The authors report that informed patient consent was obtained for publication of the clinical findings and laboratory values used herein. 

CORRESPONDENCE: 
Joy Zarandy, DO, FAAFP, Assistant Dean of Clinical Education, Assistant Professor of Family Medicine, Philadelphia College of Osteopathic Medicine (PCOM) - Georgia Campus 
625 Old Peachtree Road NW, Suwanee, GA 30024 (joyza@pcom.edu)

References 

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