Should antibiotic resistance testing be performed for patients with upper respiratory infections who have low genetic copy numbers (<10³) of colonizers such as Hemophilus influenzae, Streptococcus pneumoniae, Klebsiella pneumoniae, Moraxella catarrhalis, Staphylococcus aureus, and Streptococcus pyogenes?

Antibiotic Resistance Testing for Low Copy Numbers in URI Colonizers

Antibiotic resistance testing should NOT be performed for genetic copy numbers <10³ of these six colonizers (H. influenzae, S. pneumoniae, K. pneumoniae, M. catarrhalis, S. aureus, S. pyogenes) in upper respiratory specimens, as these levels fall well below the clinically meaningful threshold of >10⁵ CFU/mL required to distinguish true infection from colonization. 1

Rationale Based on Established Diagnostic Thresholds

• The gold standard for diagnosing bacterial sinusitis requires quantitative cultures demonstrating bacterial density of at least 10³ to 10⁴ CFU/mL from maxillary sinus aspirates, with infection confirmed only at these concentrations 1
• Culture-based diagnostic methods for respiratory specimens use thresholds of >10⁵ CFU/mL to distinguish true infection from colonization 1
• Genetic copy numbers <10³ fall substantially below this clinically meaningful threshold and do not represent acute infection 1

The Colonization vs. Infection Distinction

• These six bacterial species (S. pneumoniae, H. influenzae, M. catarrhalis, S. aureus, S. pyogenes, K. pneumoniae) are normal colonizers of the nasopharynx in both children and adults 1, 2
• By age 2 years, 44% of children have been colonized with nontypeable H. influenzae, with each strain carried for 1-7 months 1
• Approximately 78% of children are colonized with M. catarrhalis by age 2 1
• S. pneumoniae is recovered from approximately 21% of nasopharyngeal cultures in healthy children versus 32% during viral URI 1
• In adults, one of the primary respiratory pathogens is recovered from the nasopharynx of approximately 75% of individuals 1

Clinical Consequences of Testing at Low Thresholds

• Reporting values <10³ leads to unnecessary antibiotic treatment, as such low copy numbers do not cause acute infection and create confusion for providers regarding whether antibiotics are warranted 1
• The recovery of these organisms in symptomatic patients cannot confirm the presence of infection when they are present only as colonizers 1
• In healthy children, the middle meatus is colonized with the same bacterial species commonly recovered from children with sinus infections, making their presence alone insufficient for diagnosis 1

Antimicrobial Stewardship Implications

• Performing ABR testing on colonizing organisms with no clinical relevance directly contradicts antimicrobial stewardship principles 1
• The IDSA strategy to curb resistance emphasizes providing patient-specific culture and susceptibility data only when clinically meaningful 1
• Unnecessary antibiotic prescriptions driven by reporting colonizers contribute to selection pressure for resistant pathogens 1
• Reducing unnecessary testing and treatment is a cornerstone of antimicrobial stewardship programs in both emergency department and outpatient settings 1

The Resistance Development Risk

• Widespread macrolide use correlated with increased macrolide resistance in S. pyogenes (from 16.5% to peak levels), which decreased when usage was restricted 1
• A meta-analysis found that azithromycin use increased the risk of macrolide resistance among respiratory pathogens 2.7-fold compared to placebo 1
• Antimicrobial administration increases carriage of antimicrobial-resistant strains of these bacterial pathogens 1
• Treatment of colonization rather than infection accelerates resistance development without clinical benefit 1

Diagnostic Approach for True URI Bacterial Infections

• Acute bacterial rhinosinusitis should be diagnosed clinically when viral URI symptoms persist beyond 10 days or worsen after 5-7 days, not based on detection of colonizers 1
• Physical examination provides limited information, and imaging is not necessary for uncomplicated ABRS 1
• The most common bacterial species in true ABRS are S. pneumoniae, H. influenzae, and M. catarrhalis, but their presence alone at low levels does not confirm infection 1
• Throat swab cultures for S. pyogenes pharyngitis should use rapid streptococcal antigen tests as adjuncts to clinical assessment, not as standalone diagnostics 1

Resource Utilization and Cost-Effectiveness

• Eliminating ABR reflex testing for results <10³ saves an average of seven spots per ABR card and reduces usage by at least two cards per week 1
• Rapid molecular diagnostics should be reserved for situations where results will change management, not for documenting colonization 1
• The expansion of automated molecular platforms should focus on detecting pathogens at clinically relevant thresholds 1

Common Pitfalls to Avoid

• Do not interpret the mere presence of these organisms as indication for treatment—colonization rates increase during winter and viral URI periods without representing bacterial superinfection 1, 2
• Avoid reflexing to susceptibility testing when the organism burden does not meet infection thresholds, as this generates clinically irrelevant data 1
• Do not confuse microbiological (in vitro) resistance with clinical (in vivo) resistance—bacteria with low-level resistance mechanisms may be clinically susceptible when present at infection-level densities 3
• Recognize that S. aureus is both a presumed pathogen and common colonizer, making its detection at low levels particularly confusing without quantitation 1