Rapid PCR Testing Guided by Pharmacists Cuts Antibiotic Overuse in COPD Flare-Ups

Chronic obstructive pulmonary disease (COPD) affects millions of people worldwide, and when patients experience an acute exacerbation—a sudden worsening of breathlessness, cough, and sputum production—hospital admission is often the result. Because it is difficult to distinguish bacterial from viral causes at the bedside, clinicians frequently start broad-spectrum antibiotics immediately, even though respiratory viruses trigger roughly half of all exacerbations. A new prospective observational study from North Macedonia suggests that a combination of rapid molecular testing and pharmacist-led antimicrobial stewardship can change that picture dramatically, allowing most patients to stop unnecessary antibiotics within a day of admission.

The study, conducted at the University Clinic of Pulmonology and Allergology in Skopje between May and December 2025, enrolled 70 adults hospitalized with acute exacerbations of COPD. All patients received empirical intravenous antimicrobial therapy on their first day in hospital, following institutional protocols based on European Respiratory Society guidelines for lower respiratory tract infections. Before the first antibiotic dose was given, researchers collected sputum and bronchoalveolar lavage samples and analyzed them in parallel using conventional microbiological culture and the BioFire FilmArray Pneumonia Panel Plus, a multiplex polymerase chain reaction (PCR) assay capable of detecting 18 bacterial targets, nine viral targets, and seven antimicrobial resistance genes in a single run.

The diagnostic yield difference was striking. Respiratory pathogens were identified in 45 of the 70 patients (64.3 percent), and multiplex PCR detected a range of respiratory viruses—influenza A and B, respiratory syncytial virus, human rhinovirus/enterovirus, human coronavirus OC43, and human metapneumovirus—that conventional culture simply cannot routinely identify. Influenza A virus and respiratory syncytial virus were the most frequently detected pathogens, each found in ten patients, followed by Pseudomonas aeruginosa and human rhinovirus/enterovirus in nine patients each. Culture retained an important niche, however: fungal pathogens such as Candida species and Trichosporon species were detected exclusively by conventional methods, underscoring that the two approaches are complementary rather than interchangeable.

What set this study apart was the role of the clinical pharmacist. Rather than acting as a peripheral advisor, the pharmacist was directly involved in running the molecular diagnostics laboratory and interpreting the PCR results, then translating those findings into patient-specific recommendations within the antimicrobial stewardship workflow. Once PCR results became available, therapeutic modifications were typically implemented within the first 24 hours. Antibiotic discontinuation was recommended in 44 patients (62.8 percent), targeted antimicrobial optimization was performed in nine patients (12.9 percent), and empirical therapy was maintained without change in 17 patients (24.3 percent).

The specific interventions illustrate how molecular results translate into prescribing decisions. When influenza A or B was detected, the pharmacist recommended initiating oseltamivir and stopping unnecessary antibiotics. For other isolated viral infections—including respiratory syncytial virus, rhinovirus/enterovirus, metapneumovirus, and coronavirus OC43—the recommendation was straightforward antibiotic discontinuation. In cases of viral-bacterial co-infection, empirical therapy was maintained or modified according to the detected pathogens. When Pseudomonas aeruginosa was identified, the pharmacist recommended switching from moxifloxacin to ceftazidime, a targeted change driven by the organism’s resistance profile.

Perhaps the most compelling example of the technology’s value came from a single patient in whom multiplex PCR detected Serratia marcescens together with the VIM (Verona integron-encoded metallo-β-lactamase) resistance marker—a carbapenemase gene of significant clinical concern. This detection prompted a switch from moxifloxacin to ciprofloxacin, demonstrating that rapid molecular diagnostics can inform antimicrobial choices well beyond simple pathogen identification, flagging resistance mechanisms early enough to shape therapy in real time.

On the outcome side, the median hospital stay was 12 days, with a range of 5 to 25 days. Laboratory markers of inflammation improved substantially by discharge: median C-reactive protein fell from 16.05 mg/L at admission to 3.0 mg/L, and leukocyte counts and lactate dehydrogenase levels also declined. Using point-biserial correlation analysis with Bonferroni correction for multiple comparisons, only one microbiological variable remained significantly associated with prolonged hospitalization: infection with human rhinovirus/enterovirus. Patients positive for this virus stayed a median of 20 days compared with 11 days for those without it, a difference confirmed by non-parametric sensitivity analysis.

The rhinovirus finding deserves careful interpretation. Only nine patients tested positive for human rhinovirus/enterovirus, and most detections occurred in the context of co-infection—five patients had concurrent bacterial pathogens such as Streptococcus pneumoniae, Pseudomonas aeruginosa, Escherichia coli, or Haemophilus influenzae, and two had additional viral co-detections. Only two patients had rhinovirus/enterovirus as a single pathogen. The longest hospitalization in the study, 25 days, occurred in a patient with combined respiratory syncytial virus, rhinovirus/enterovirus, and E. coli infection. This pattern suggests that the association may reflect the greater clinical complexity of mixed infections rather than an independent effect of rhinovirus alone, though previous research has shown that rhinovirus can enhance airway inflammation, impair antibacterial host defenses, and facilitate secondary bacterial infection in COPD.

The study has clear limitations that temper its conclusions. The single-arm observational design, without a comparator group receiving stewardship without PCR guidance, cannot establish the independent contribution of molecular diagnostics to outcomes. The single tertiary-care center and modest sample size limit generalizability, several pathogens were detected too infrequently for meaningful statistical analysis, and the study captured only in-hospital outcomes without long-term follow-up for mortality or readmissions. These caveats notwithstanding, the work provides real-world evidence from a setting where conventional culture remains the diagnostic cornerstone and advanced molecular infrastructure is still emerging—a context highly relevant to many low- and middle-income health systems.

The broader significance lies in what the model demonstrates about workflow integration. Pharmacist-led stewardship programs have previously been shown to improve antibiotic prescribing quality in COPD exacerbations, and multiplex PCR has been shown to accelerate pathogen detection in pneumonia. This study brings the two together, positioning the clinical pharmacist as the interpretive bridge between the molecular laboratory and the bedside. With nearly two-thirds of patients able to stop antibiotics based on PCR-guided recommendations, and with resistance markers detectable within hours rather than days, the approach offers a concrete template for how rapid diagnostics and stewardship expertise can be combined to curb unnecessary antimicrobial exposure in one of the most common reasons for hospital admission worldwide.

Subject of Research: Integration of multiplex PCR diagnostics into pharmacist-led antimicrobial stewardship for COPD exacerbations

Article Title: Clinical pharmacist-led multiplex polymerase chain reaction diagnostics as a tool for antimicrobial stewardship in acute exacerbations of chronic obstructive pulmonary disease

Article References: Nakovska, O. K., Mihajloska, E., Debreshlioska, A., Karkinski, D., Tatabitovska, A., Grozdanova, A., & Shuturkova, L. (2026). Clinical pharmacist-led multiplex polymerase chain reaction diagnostics as a tool for antimicrobial stewardship in acute exacerbations of chronic obstructive pulmonary disease. Pharmacia, 73, Article e203025. https://doi.org/10.3897/pharmacia.73.e203025

Image Credits: AI Generated

DOI: 10.3897/pharmacia.73.e203025

Keywords: COPD, multiplex PCR, antimicrobial stewardship, clinical pharmacist, respiratory viruses, antibiotic de-escalation, human rhinovirus, Pseudomonas aeruginosa, antimicrobial resistance, hospital length of stay, molecular diagnostics, Clinical