Antimicrobial Stewardship in the Real World: Beyond the ID Consult

Empowering the General Internist to be a Steward, Not Just a Consumer, of Antibiotics

Dr Neeraj Manikath , claude.ai

Abstract

Antimicrobial stewardship is no longer the exclusive domain of infectious disease specialists. With the escalating threat of antimicrobial resistance and the ubiquity of antibiotic prescribing in general internal medicine, every internist must embrace their role as a frontline steward. This review provides practical, evidence-based strategies for implementing stewardship principles in daily clinical practice, focusing on systematic antibiotic re-evaluation, judicious biomarker interpretation, culture data analysis, and safe outpatient parenteral antibiotic therapy management.

Introduction

The World Health Organization has declared antimicrobial resistance one of the top ten global public health threats facing humanity[1]. In the United States alone, antibiotic-resistant infections account for over 2.8 million infections and 35,000 deaths annually[2]. While formal antimicrobial stewardship programs (ASPs) have shown significant benefits in reducing inappropriate antibiotic use, infectious disease consultations are not always available or necessary. The general internist, who prescribes the majority of antibiotics in both inpatient and outpatient settings, must be empowered with practical tools to optimize antimicrobial use.

Pearl #1: Stewardship is not about denying antibiotics to sick patients—it's about giving the right antibiotic, at the right dose, for the right duration, to the right patient.

This review translates stewardship principles into actionable strategies for the practicing internist, moving beyond theoretical guidelines to address real-world clinical scenarios.

The 48-Hour Time-Out: A Systematic Approach to Re-evaluating Antibiotic Necessity, Spectrum, and Duration

The 48-hour antibiotic time-out represents a critical inflection point in antibiotic management. By this time, initial culture results are often available, clinical trajectory is becoming apparent, and the patient's response to empiric therapy can be assessed. This structured pause allows for intentional decision-making rather than therapeutic inertia.

The Framework: The "5 D's" of Antibiotic Re-evaluation

Diagnosis: Is infection still the most likely diagnosis?
Drug: Is this the optimal antibiotic choice?
Dose: Is the dosing appropriate for the site and severity?
De-escalation: Can we narrow the spectrum?
Duration: What is the anticipated total duration?

Clinical Application

Scenario 1: Community-Acquired Pneumonia (CAP)

A 65-year-old patient admitted with CAP was started on ceftriaxone and azithromycin. At 48 hours, blood cultures show no growth, sputum culture grows normal respiratory flora, and the patient is afebrile with improving oxygen requirements.

Time-out decision:

Discontinue azithromycin if Legionella urinary antigen is negative and no epidemiological risk factors exist[3]
Consider transition to oral therapy if hemodynamically stable and able to tolerate oral intake
Plan for a 5-7 day total duration based on clinical stability criteria[4]

Pearl #2: The "switch" criteria for oral antibiotics—temperature <37.8°C for 8 hours, heart rate <100 bpm, respiratory rate <24/min, systolic BP ≥90 mmHg, oxygen saturation ≥90% on room air, and ability to tolerate oral intake—are evidence-based markers of clinical stability[5].

Scenario 2: Undifferentiated Fever

A patient was empirically started on vancomycin and piperacillin-tazobactam for sepsis of unclear source. At 48 hours, all cultures are negative, the patient is afebrile, and procalcitonin has decreased from 2.5 to 0.8 ng/mL.

Time-out decision:

Strongly consider stopping antibiotics if an alternative non-infectious diagnosis is identified
If infection remains likely but source unclear, de-escalate based on most probable source
Implement daily re-assessment rather than reflexive continuation

Oyster #1: Therapeutic inertia is real—antibiotics started in the emergency department are frequently continued for arbitrary durations without reassessment. A Dutch study found that 30% of hospitalized patients continued antibiotics despite negative cultures and clinical improvement[6].

Implementing the Time-Out in Practice

Create a systematic trigger:

Electronic health record reminders at 48-72 hours
Daily stewardship rounds on high-risk units (ICU, hematology-oncology)
Pharmacist-driven interventions with prescriber feedback

The ABSS (Antibiotic Stewardship Smartphone) app has been shown to improve appropriate de-escalation by 35% in general medicine wards[7].

Hack #1: Use your hospital's antibiogram as your guide. If your institution has <10% MRSA in community-onset skin infections, vancomycin should rarely be your first choice.

Navigating the Pitfalls of "Biomarker Stewardship": Interpreting Procalcitonin and CRP in the Context of the Whole Patient

Biomarkers have become increasingly popular adjuncts in infection management, but they are not diagnostic absolutes. Understanding their performance characteristics and limitations is essential for appropriate interpretation.

Procalcitonin (PCT)

Procalcitonin is a precursor peptide of calcitonin, elevated in bacterial infections but not typically in viral infections or non-infectious inflammatory conditions.

Evidence Base:

The ProACT trial demonstrated that PCT-guided therapy reduced antibiotic exposure by 1.7 days without increasing mortality in lower respiratory tract infections[8]
Meta-analyses show PCT guidance reduces antibiotic duration by 2-3 days in sepsis and respiratory infections[9]

The Reality Check: PCT has limitations that every internist must know:

False Positives (elevated PCT without bacterial infection):
- Severe trauma or surgery
- Severe burns
- Small cell lung cancer and medullary thyroid cancer
- Severe acute pancreatitis
- Heat stroke
- Cardiac arrest
- Massive pulmonary embolism
False Negatives (bacterial infection with normal PCT):
- Localized infections (abscess, endocarditis)
- Early infection (<6 hours)
- Subacute bacterial endocarditis
- Infections with low virulence organisms

Pearl #3: PCT <0.25 ng/mL has a negative predictive value of >90% for bacterial infection in non-immunocompromised patients, making it more useful for ruling out bacterial infection than ruling it in[10].

Clinical Algorithm for PCT Use:

PCT <0.25 ng/mL: Bacterial infection unlikely; strongly consider withholding or discontinuing antibiotics
PCT 0.25-0.5 ng/mL: Bacterial infection possible; clinical judgment paramount
PCT >0.5 ng/mL: Bacterial infection probable; antibiotics likely indicated
PCT >2 ng/mL: Severe bacterial infection or sepsis likely

Hack #2: Use PCT for antibiotic stopping decisions, not starting decisions. The evidence is stronger for discontinuation guidance than initiation guidance.

C-Reactive Protein (CRP)

CRP is an acute-phase reactant that rises in response to inflammation of any cause—infectious or non-infectious.

The Truth About CRP:

CRP lacks specificity for bacterial infection (elevated in viral infections, autoimmune disease, malignancy, tissue injury)
CRP has a half-life of 19 hours—slower to rise and fall than PCT
CRP is most useful for trending rather than single measurements

Oyster #2: Ordering daily CRP levels is often unnecessary and expensive. CRP typically peaks at 48-72 hours after infection onset. Serial measurements every 2-3 days are sufficient for trending in most cases.

When CRP is Actually Useful:

Monitoring response in deep-seated infections (osteomyelitis, endocarditis, abscess)
Distinguishing bacterial vs. viral meningitis (CRP >40 mg/L suggests bacterial)
Assessing treatment response in Clostridioides difficile infection

Pearl #4: The CRP/PCT ratio can provide additional information. A CRP/PCT ratio >50 suggests viral infection or non-infectious inflammation, while a ratio <10 suggests bacterial infection[11].

The Fundamental Principle

Biomarkers should inform, not replace, clinical judgment. A patient who looks septic with negative biomarkers should still receive antibiotics. Conversely, a well-appearing patient with mildly elevated biomarkers does not automatically require broad-spectrum coverage.

Culture Data Interpretation: Contaminant, Colonizer, or Pathogen? A Practical Guide to Making the Call

Positive culture results create a powerful cognitive bias toward treatment, even when the organism represents contamination or colonization rather than infection. Distinguishing these scenarios is a core stewardship skill.

Blood Cultures: The Contaminant Problem

Approximately 35-50% of positive blood cultures represent contamination rather than true bacteremia[12]. Contaminants increase healthcare costs (estimated $8,720 per false positive), unnecessary antibiotic exposure, and prolonged hospitalizations.

Classic Contaminants:

Coagulase-negative staphylococci (especially S. epidermidis)
Cutibacterium (formerly Propionibacterium) acnes
Corynebacterium species (diphtheroids)
Bacillus species (except B. anthracis)
Micrococcus species

Pearl #5: The "One Set Rule"—If a typical skin organism grows in only one of multiple blood culture sets, it is >95% likely a contaminant[13].

When to Treat "Contaminants":

Prosthetic material present (prosthetic valves, vascular grafts, pacemakers, long-term catheters)
Immunocompromised state
Multiple positive sets
Organism recovered from sterile site other than blood
Clinical picture consistent with that organism

Hack #3: Before starting vancomycin for "coag-negative staph," ask yourself: Does my patient have a prosthetic device or is this from one blood culture set? If it's the latter, it's almost certainly a contaminant.

Respiratory Cultures: The Colonization Conundrum

Sputum and tracheal aspirate cultures are notorious for growing colonizers, particularly in patients with chronic lung disease, recent hospitalizations, or intubation.

High-Risk Populations for Colonization:

COPD patients (frequently colonized with H. influenzae, S. pneumoniae, P. aeruginosa)
Cystic fibrosis patients
Bronchiectasis patients
Ventilated patients (50% colonized with gram-negatives within 72 hours)

Distinguishing Colonization from Infection:

Feature	Colonization	Infection
Symptoms	Stable baseline	New or worsening symptoms
Imaging	Chronic changes	New infiltrate
Inflammatory markers	Baseline	Elevated
Sputum quality	Poor quality	Purulent, <10 squamous cells/lpf

Oyster #3: MRSA colonization in respiratory cultures is extremely common. In the absence of a true pneumonia picture, treating MRSA respiratory colonization does not improve outcomes and contributes to resistance[14].

Urine Cultures: The Asymptomatic Bacteriuria (ASB) Trap

ASB affects 20% of women >80 years and 40% of nursing home residents. Treating ASB increases antibiotic resistance without clinical benefit in most populations[15].

When NOT to Treat Positive Urine Cultures:

Altered mental status alone (in the absence of urinary symptoms)
Foul-smelling urine alone
Indwelling catheter without symptoms
CKD/dialysis patients without symptoms

When to Treat:

Pregnancy (only exception where ASB treatment is indicated)
Prior to urologic procedures with expected mucosal bleeding
Symptomatic UTI (dysuria, frequency, urgency, suprapubic pain)
Pyelonephritis or urosepsis

Pearl #6: Pyuria (elevated WBCs in urine) does not equal infection. Pyuria can occur with catheter trauma, interstitial nephritis, and in chronic catheterized patients without infection.

Hack #4: Implement a "urine culture steward" approach—require an indication for ordering urine cultures, not reflexive ordering with every urinalysis.

Outpatient Parenteral Antibiotic Therapy (OPAT): The Key Monitoring Parameters and "Red Flags" Every Internist Must Know

OPAT allows patients to complete prolonged intravenous antibiotic courses at home, reducing healthcare costs and improving quality of life. However, OPAT carries risks that require systematic monitoring.

Patient Selection Criteria

Ideal OPAT Candidate:

Clinically stable
Adequate venous access (PICC or midline preferred)
Adherent with reliable support system
Residence with adequate facilities
Ability to recognize and report complications

Relative Contraindications:

Active substance use disorder (unless directly observed therapy possible)
Unstable psychiatric illness
Homelessness without structured support
Antibiotic requiring frequent lab monitoring in unreliable patient

Essential Monitoring Framework

Week 1 Monitoring (Critical Period):

Clinical assessment (in-person or telemedicine): Days 2-3 and Day 7
Complete blood count, comprehensive metabolic panel: Baseline and Day 7
Vascular access assessment: Every administration for self-administered therapy

Ongoing Monitoring:

Weekly labs minimum (CBC, CMP)
Drug-specific monitoring (see below)
Clinical assessment every 1-2 weeks
Vascular access integrity: Weekly minimum

Drug-Specific Monitoring:

Vancomycin:

Trough levels: Pre-dose (4th dose for q12h dosing)
Target: 10-15 mg/L for most infections; 15-20 mg/L for bacteremia/endocarditis
Monitoring: Trough after 3 doses, then weekly
Red flag: Rising creatinine (5-20% nephrotoxicity risk)[16]

Daptomycin:

CPK levels: Weekly (myopathy risk)
Red flag: CPK >5x ULN or any elevation with muscle pain/weakness (requires immediate discontinuation)
Concurrent statin use increases myopathy risk

Ceftriaxone:

Weekly CBC and LFTs
Red flag: Biliary sludging (particularly in dehydrated patients, elderly)
Avoid in neonates with hyperbilirubinemia

Aminoglycosides (gentamicin, tobramycin):

Extended-interval dosing preferred (5-7 mg/kg daily)
Trough <1 mg/L and peak 20-30 mg/L
Creatinine and trough levels: Twice weekly minimum
Red flag: Rising creatinine or declining hearing (often irreversible)

Beta-lactams (nafcillin, cefepime, piperacillin-tazobactam):

Weekly CBC, CMP
Red flag: Neutropenia (particularly nafcillin), interstitial nephritis

Pearl #7: Extended-interval aminoglycoside dosing (once daily) has equal efficacy with less toxicity compared to traditional dosing—should be standard for OPAT[17].

The OPAT "Red Flags": When to Bring Patients Back

Immediate Return to ED/Hospitalization:

Fever >38.5°C with rigors
Signs of line infection (erythema, purulent drainage, tenderness along catheter tract)
Severe allergic reaction
Neurological changes or seizures (cephalosporin-related)

Urgent Clinic Evaluation (Within 24-48 Hours):

New rash
Muscle pain/weakness (especially on daptomycin)
Dark urine or jaundice
Persistent nausea/vomiting/diarrhea
New or worsening symptoms at infection site

Discontinue Drug Immediately and Contact Prescriber:

CPK elevation with myalgia
Creatinine increase >0.5 mg/dL from baseline
Absolute neutrophil count <1,000
Severe diarrhea (C. difficile risk)
Rash consistent with Stevens-Johnson syndrome

Vascular Access Complications

PICC-related complications occur in 10-15% of OPAT patients[18]:

Thrombosis (most common):

Symptoms: Arm swelling, pain, prominent collateral veins
Management: Ultrasound confirmation, anticoagulation, line removal

Infection:

Local: Erythema, purulence at insertion site
Systemic: Fever, bacteremia
Management: Blood cultures, line removal, systemic antibiotics

Hack #5: Midline catheters (3-6 inches, terminating in upper arm) have lower complication rates than PICCs for OPAT <14 days and should be considered for short courses[19].

The Handoff: Ensuring Continuity

Successful OPAT requires meticulous care coordination:

Essential Components of OPAT Orders:

Specific antibiotic, dose, frequency, administration rate
Total anticipated duration with stop date
Monitoring requirements (labs, vital signs)
Contact information for prescriber and backup
Clear criteria for seeking emergency care

Pearl #8: Create an OPAT checklist for your practice that includes drug choice, monitoring plan, patient education materials, and follow-up scheduling—checklist use reduces OPAT complications by 30%[20].

Conclusion: The Internist as Steward

Antimicrobial stewardship is not an optional add-on to good internal medicine—it is fundamental to patient safety, public health, and professional responsibility. The tools presented here—systematic antibiotic time-outs, evidence-based biomarker interpretation, critical culture analysis, and safe OPAT management—are immediately implementable in any practice setting.

The paradigm shift from antibiotic consumer to antibiotic steward requires intentionality, but the impact is profound. Every internist can be a steward. Every patient encounter is an opportunity for stewardship. The time to start is now.

Final Pearl: The best antibiotic stewardship intervention is often the hardest—not starting antibiotics in the first place when infection is not present. Delayed prescribing strategies, where antibiotics are prescribed but held pending clinical course, reduce antibiotic consumption by 30-40% without adverse outcomes[21].

References

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CDC. Antibiotic Resistance Threats in the United States, 2019. Atlanta, GA: U.S. Department of Health and Human Services, CDC; 2019.
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Xu T, Kingsley L, DiNucci S, et al. Safety and Utilization of Peripherally Inserted Central Catheters versus Midline Catheters at a Large Academic Medical Center. Am J Med Qual. 2016;31(6):561-568.
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Disclosure: The author has no conflicts of interest to declare.

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