Genomic Load from Sputum Samples and Nasopharyngeal Swabs for Diagnosis of Pneumococcal Pneumonia in HIV-Infected Adults

Abstract

Quantitative lytA real-time PCR (rtPCR) results from nasopharyngeal (NP) swabs distinguish community-acquired pneumococcal pneumonia (CAP) from asymptomatic colonization. The use of an optimized cutoff value improved pneumococcal etiology determination compared to that of traditional diagnostic methods. Here, we compare the utility of lytA rtPCR from induced sputum and from NP swabs. Pneumococcus was considered the cause of CAP in HIV-infected South African adults if blood culture, induced-sputum culture or Gram stain, urine antigen test, or whole-blood lytA rtPCR revealed pneumococcus or if lytA rtPCR from NP swabs gave a result of >8,000 copies/ml. lytA rtPCR was also performed on induced sputum. Pneumococcus was detected by lytA rtPCR from sputum in 149 (67.1%) of 222 patients with available induced sputum, whereas the results of either Gram stain or culture of sputum were positive in 105 of 229 patients (45.9%; P < 0.001). The mean copy numbers from sputum were higher when the sputum cultures were positive than when the sputum cultures were negative (7.9 versus 5.6 log 10 copies/ ml; P < 0.001). Against the composite diagnostic standard, a cutoff value of 10,000 copies/ml for good-quality sputum lytA rtPCR had a sensitivity of 78.1% and a specificity of 80.0%. This cutoff value performed similarly to the previously identified cutoff value of 8,000 copies/ml for NP swab lytA rtPCR (area under the curve receiver operating characteristic [AUC-ROC], 80.4% for sputum of any quality versus 79.6% for NP swabs). The AUC-ROC for good-quality sputum was 83.2%. Overall, lytA rtPCR performs similarly well on induced sputum as on NP swabs for most patients but performs slightly better if good-quality sputum can be obtained. Due to the ease of specimen collection, NP swabs may be preferable for the diagnosis of pneumococcal pneumonia.

Assessing the diagnostic accuracy of PCR-based detection ofStreptococcus pneumoniaefrom nasopharyngeal swabs collected for viral studies in Canadian adults hospitalised with community-acquired pneumonia: a Serious Outcomes Surveillance (SOS) Network of the Canadian Immunization Research (CIRN) study

“…Future studies should consider the effects of possible confounding factors such as the time of collection, prior antibiotic, progression of disease and host factors such as comorbidities or immunosuppression. [24][25][26][27] While this study evaluated the performance for S. pneumoniae detection by PCR in NP swab collected for viral studies, it was recognised that other specimen types, such as oral and oropharyngeal swabs, were previously shown to perform better than sampling from the nasopharynx to assess pneumococcal colonisation. [28][29][30] Since the performance of NP swab PCR is affected by the results of its comparator, a future studies would benefit from a direct comparison between PCR-based detection of pneumococcal DNA in NP swabs and concurrent quantitative S. pneumoniae from culture swabs collected from the nasopharynx.…”

The potential of molecular diagnostics and serum procalcitonin levels to change the antibiotic management of community-acquired pneumonia

“…Studies either suggest or refute a correlation of pathogen density ("load") with invasive disease (Collins et al, 2016). Seroconversion is often the "gold standard" but not helpful during the acute illness (Albrich et al, 2014).…”

The clinical impact of the detection of potential etiologic pathogens of community-acquired pneumonia

“…The previous studies designed to determine the etiology of CAP have not routinely used NP swabs PCR testing for detection of S. pneumoniae. In a rigorous pneumonia study in HIV-infected adults, NP swabs performed as well as PCR probes of sputum (Albrich et al, 2014). Hence, with the difficulty of obtaining valid sputum specimens, NP samples have the advantage of ease of specimen collection.…”