What is the appropriate first‑line antimicrobial regimen and dosing for a 55‑year‑old man (90 kg) with Salmonella enterica bacteremia and mild renal impairment (serum creatinine 135 µmol/L)?

Treatment of Salmonella enterica Bacteremia with Mild Renal Impairment

For this 55-year-old man with Salmonella enterica bacteremia and a serum creatinine of 135 µmol/L (approximately 1.5 mg/dL, CrCl ~60 mL/min), ciprofloxacin 400 mg IV every 12 hours is the first-line treatment, with ceftriaxone 2 g IV daily as the alternative if fluoroquinolone resistance is present. 1

First-Line Antimicrobial Selection

Preferred Regimen: Fluoroquinolone

• Ciprofloxacin 400 mg IV every 12 hours is the guideline-recommended first-line agent for invasive Salmonella infections 1
• Alternatively, ciprofloxacin 500 mg PO every 12 hours can be used if the patient tolerates oral intake and has uncomplicated bacteremia 1
• No dose adjustment is required for this level of renal function (CrCl ~60 mL/min) 1

Alternative Regimen: Third-Generation Cephalosporin

• Ceftriaxone 2 g IV once daily should be used if the isolate demonstrates nalidixic acid resistance or fluoroquinolone resistance 1
• Ceftriaxone requires no renal dose adjustment and is particularly useful given the patient's mild renal impairment 1
• This agent is increasingly important as fluoroquinolone resistance has emerged globally in Salmonella species 2

Treatment Duration

• 6–8 weeks of total antimicrobial therapy is recommended for Salmonella bacteremia 1
• This extended duration (compared to typical gram-negative bacteremia) is necessary because Salmonella has a propensity for endovascular seeding and metastatic complications 3
• Patients older than 60 years with nontyphoidal Salmonella bacteremia have a 23% risk of endovascular infection, warranting the longer treatment course 3

Critical Diagnostic Workup Before Finalizing Treatment

Rule Out Endovascular Complications

• Obtain CT imaging of the chest, abdomen, and pelvis to exclude mycotic aneurysm, particularly given the patient's age (>50 years) and any atherosclerotic risk factors 3
• Perform echocardiography (transesophageal preferred) to exclude endocarditis, as underlying cardiac disease increases this risk substantially 3
• Fever, unremitting sepsis, or "breakthrough" bacteremia during therapy are red flags for endovascular infection 3

Confirm Microbiologic Clearance

• Repeat blood cultures 2–4 days after initiating therapy to document clearance of bacteremia 1
• Persistent positive cultures mandate investigation for a deep-seated focus (abscess, osteomyelitis, endocarditis) 3

Assess Antimicrobial Susceptibility

• Obtain full susceptibility testing including ciprofloxacin MIC because decreased fluoroquinolone susceptibility (MIC 0.12–0.5 µg/mL) is common and associated with treatment failure 2
• The 2013 CLSI lowered ciprofloxacin breakpoints for Salmonella; isolates previously called "susceptible" may now be intermediate or resistant 2
• If fluoroquinolone resistance is confirmed, switch to ceftriaxone 2 g IV daily 1

Renal Function Monitoring

Salmonella-Associated Nephrotoxicity

• Salmonella gastroenteritis causes renal dysfunction in 36% of hospitalized adults through mechanisms independent of dehydration or rhabdomyolysis 4
• Monitor serum creatinine 2–3 times weekly during the first 2 weeks of therapy, as the infection itself may worsen renal function 4
• Kidney function typically recovers with appropriate antimicrobial therapy 4

Avoid Nephrotoxic Combinations

• Do not add aminoglycosides (e.g., gentamicin) to the regimen, as they provide no benefit for Salmonella bacteremia and significantly increase nephrotoxicity risk in a patient with baseline renal impairment 5
• If vancomycin were needed for another indication, renal function would require monitoring 2–3 times weekly 5

Common Pitfalls to Avoid

Do Not Undertreat Duration

• Avoid shortening therapy to 2 weeks, even if blood cultures clear rapidly, because Salmonella has high rates of relapse and metastatic seeding when treatment is abbreviated 3
• The 6–8 week duration applies even to "uncomplicated" bacteremia without identified endovascular focus 1

Do Not Use Empiric Broad-Spectrum Therapy Unnecessarily

• Once Salmonella is identified and susceptibilities are known, de-escalate from empiric broad-spectrum agents (e.g., piperacillin-tazobactam, carbapenems) to targeted fluoroquinolone or ceftriaxone therapy 1
• Prolonged use of carbapenems or other broad-spectrum agents increases risk of Clostridioides difficile infection and antimicrobial resistance 1

Recognize Fluoroquinolone Resistance Patterns

• Do not assume fluoroquinolone susceptibility based on older breakpoints or empiric treatment success in the first 48 hours 2
• Chromosomal mutations in the quinolone resistance-determining region are increasingly common and lead to clinical failure despite in vitro "susceptibility" by outdated criteria 2

Address Underlying Structural Abnormalities

• Salmonella bacteremia in adults typically indicates an underlying predisposition: atherosclerotic vascular disease (mycotic aneurysm risk), nephrolithiasis (urinary tract seeding), or immunosuppression 6, 3
• Investigate for urinary tract involvement if the patient has a history of nephrolithiasis or recurrent UTIs, as non-typhoidal Salmonella can seed the urinary tract hematogenously 6

Transition to Oral Therapy

• Switch to oral ciprofloxacin 500 mg every 12 hours after clinical improvement (afebrile ≥48 hours, hemodynamically stable, negative repeat blood cultures) to complete the 6–8 week course 1
• Oral fluoroquinolones have excellent bioavailability (>70%) and are appropriate for step-down therapy in Salmonella bacteremia 1
• If ceftriaxone was used due to fluoroquinolone resistance, continue IV therapy for the full duration because oral β-lactams have poor bioavailability and should not be used for invasive Salmonella infections 1