lytA Quantitative PCR on Sputum and Nasopharyngeal Swab Samples for Detection of Pneumococcal Pneumonia among the Elderly
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Real-time quantitative PCR (qPCR) assay of sputum or nasopharyngeal specimens has shown promising results in the detection of pneumococcal community-acquired pneumonia (PncCAP). We applied qPCR for the autolysin gene (lytA) and compared sputum and nasopharyngeal swab (NPS) pneumococcal loads in elderly patients with community-acquired pneumonia (CAP), and specifically in patients with PncCAP, to those in patient groups with other respiratory diseases. We studied patients aged ≥65 years with radiologically confirmed CAP, clinical CAP not retrospectively radiologically confirmed, other acute respiratory infections, or stable chronic lung disease. Pneumococcal etiology of CAP was ascertained by using a combination of multiple diagnostic methods. We analyzed sputum and NPS specimens by lytA qPCR with 104 pneumococcal genome equivalents (GE)/ml as a cutoff for positivity. Among PncCAP patients, lytA qPCR detected pneumococci in 94% of the sputum samples and in large quantities (mean, 6.82 ± 1.02 log10 GE/ml) but less frequently in NPS (44%) and in smaller quantities (5.55 ± 0.92 log10 GE/ml). In all other patient groups, ≤10% of the sputum samples and <5% of the NPS samples were lytA qPCR positive; but when they were positive, the sputum pneumococcal loads were similar to those in the PncCAP patients, suggesting a pneumococcal etiology in these patients. This was supported by other pneumococcal assay results. Overall, sputum lytA qPCR positivity was more common in PncCAP patients than in the other patient groups, but the quantitative results were mainly similar. NPS lytA qPCR was less sensitive than sputum lytA qPCR in detecting PncCAP.Keywords:
Pneumococcal pneumonia
Etiology
Streptococcus pneumoniae is one of most common causes of community-acquired pneumonia. We evaluated a newly available rapid immunochromatographic test to detect S. pneumoniae in urine samples verifying its importance in the diagnosis of pneumococcal pneumonia. Our data, obtained from 104 patients with community-acquired pneumonia, show that Now S. pneumoniae Urinary Test is characterized by a sensitivity value of 77.7%, a specifity of 98.8%: positive and negative predictive values are 93.3% and 95.5%, respectively. In conclusion, Now S. pneumoniae Urinary Test should be a useful test to establish the etiology of community-acquired pneumonia.
Etiology
Pneumococcal pneumonia
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Medical microbiology
Pneumococcal pneumonia
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Streptococcus pneumoniae is the leading cause of community-acquired pneumonia worldwide and is the most likely causative pathogen in patients with community-acquired pneumonia admitted to the intensive care unit. Bacteremic pneumococcal pneumonia is an advanced stage of severe pneumococcal pneumonia. Improvement in the management of bacteremic pneumococcal pneumonia has the potential for improving the survival for severe pneumococcal pneumonia.Non-culture methods, especially the Binax urinary antigen test, can increase the diagnostic yield for pneumococcal pneumonia, allowing targeted antimicrobial therapy (specifically penicillin). In-vitro resistance to penicillin has increased over the past decade; however, it has not led to clinical failure when used for pneumococcal pneumonia.Hospitalized patients with community-acquired pneumonia should have blood cultures obtained to confirm the possibility of bacteremic pneumococcal pneumonia. Based on pharmacodynamic properties, parenteral penicillin remains the drug of choice to treat pneumococcal pneumonia regardless of in-vitro resistance. Combination antimicrobial therapy will likely improve survival of patients with bacteremic pneumococcal pneumonia among the subset of critically ill patients.
Pneumococcal pneumonia
Bacterial pneumonia
Empiric therapy
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Community-acquired pneumonia is still serious disease with morbidity estimated at 5-12 per thousand adult population. The proper management of patients with pneumonia is crucial for effectiveness of therapy and decrease of mortality. There are few classifications of pneumonia severity. In clinical practice the most useful is division on community and hospital acquired pneumonia. This paper concerns recommendations and crucial information for diagnosis and treatment of community-acquired pneumonia based upon publications and own clinical experience.
Bacterial pneumonia
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Pneumococcal pneumonia
Bacteremia
Bacterial pneumonia
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Ceftriaxone-resistant Streptococcus pneumoniae (CRSP) (minimal inhibitory concentration > 1 mcg/mL) is a growing major concern in the optimal selection of empirical antimicrobial treatment of community-acquired pneumonia (CAP). It has been estimated that up to 37.9% of S. pneumoniae are resistant to ceftriaxone in the United States in 2012,1 with a mean of 19.2% in Europe including greater than 25% in Eastern Europe (Bulgaria, Romania, and Turkey) in 20112 and 18.5% in China in 2011.3 This high rate of CRSP has been in part correlated with the introduction of the PCV7 in 2001 and of PCV13 in 2010 and the selection of serotypes 19A, 6C, and 22F.4,5 The increasing use of antimicrobials in humans and in food-producing animals among others is expected to contribute to the rising rate of CRSP.6 Mutation of cell wall penicillin-binding protein (PBP), particularly PBP1a, PBP2x, and PBP2b, was associated with CRSP.7 Because S. pneumoniae is the most common etiologic agent of CAP, physicians should optimize the empirical therapy of CAP in areas with a high rate of CRSP. Wenzler et al8 examined in this issue the clinical outcomes of patients with CRSP (minimal inhibitory concentration > 1 mcg/mL) versus ceftriaxone-susceptible S. pneumoniae in adult patients with pneumonia and respiratory culture positive for S. pneumoniae. Regardless of the sample size limitation, this study has striking findings. None of the patients with CRSP infection had 90 days of previous exposure of ceftriaxone. Time to clinical cure was longer in patients with CRSP (4 [1–5] vs 8 [3–12] days, P = 0.51), and length of stay was longer for patients with CRSP (17 [9–23] vs 9 [7–13] days, P = 0.46). The empirical treatment was changed in 50% of the patients with CRSP infection versus 0% in those with ceftriaxone-susceptible pneumoniae infection. A 50% of patients with CRSP infection were treated with fluoroquinolones, and 70% were treated with either vancomycin or linezolid. Among other findings, 70% of the patients with CRSP infection had pneumonia severity index of IV or greater. Overall, both groups had similar clinical outcomes although these outcomes may not have been similar if patients with CRSP infection were treated with ceftriaxone according to CAP treatment guidelines. Large prospective studies are needed to validate the optimal treatment of CRSP CAP. Current options for the treatment of CRSP CAP are fluoroquinolones, vancomycin, linezolid, and ceftaroline. Ceftaroline is the first of the growing group of active cephalosporins against methicillin-resistant Staphylococcus aureus and it also has activity against CRSP. Ceftaroline showed sustained bactericidal activity against CRSP in a pharmacokinetics and pharmakodynamics model study.9 This ceftaroline activity was validated in a rabbit model at a simulated human dose of 20 mg/kg by reducing 6 log units of CRSP in the lungs.10 Furthermore, a second analysis of studies focus 1 and 2 revealed that patients with S. pneumoniae CAP treated with ceftaroline had more favorable outcome than patients treated with ceftriaxone (odds ratio, 2.6; 95% confidence interval, 1.11–6.17; P = 0.0286).11 An approach in the empirical therapy of CRSP CAP could be a similar strategy used for bacterial meningitis by adding vancomycin to ceftriaxone treatment. Current Infectious Diseases Society of America guidelines do not recommend the use of vancomycin in cases with severe CAP nor CRSP. Vancomycin has a limited bactericidal activity when compared with β-lactams. Although levofloxacin and moxifloxacin have effective activity against CRSP, fluoroquinolones use has been reported to trigger higher rates of multiple drug resistance Pseudomonas, methicillin-resistant Staphylococcus aureus, and Clostridium difficile infections.12 In contrast to linezolid, ceftaroline has a spectrum similar to ceftriaxone covering gram-negative rods, including those etiologic organisms of CAP such as Klebsiella spp., Haemophilus spp., and Moraxella. In summary, physicians should consider antimicrobials with activity against CRSP in patients with CAP residing in areas with substantial prevalence of CRSP, in particular, those from the US southern states, having history of previous antibiotic therapy, and being immunocompromised.1,6 This concern is critical in patients with advanced comorbidities and increased risk for poor outcomes. Current data support more the use of ceftaroline treatment in cases with suspected CRSP pneumonia. Physicians should be cautious to use fluoroquinolones treatment of CRSP infection given the risk for antimicrobial resistance. Other treatment options include vancomycin although it has limited bactericidal activity compared with β-lactams and linezolid, which has the advantage of 100% of intestinal absorption that makes it a candidate for oral therapy.
Pneumococcal pneumonia
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Community-acquired pneumonia (CAP) is a frequent cause of hospitalization in adults. Streptococcus pneumoniae is the most commonly identified pathogen in CAP whereas Legionella pneumophilia is infrequently identified in CAP. Although co-infections have been previously described, the presence of both pneumococcus and legionella together is rare. We present a patient with positive urinary antigens for both Streptococcus pneumoniae and Legionella pneumophilia serogroup 1, indicating an unusual co-infection.
Legionella
Legionnaires' disease
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Community-acquired pneumonia (CAP) is an important cause of morbidity and mortality in all age groups throughout the world. Bacterial pneumonia is the most described, with Streptococcus pneumoniae being the most important pathogen in all age groups. Viruses are also recognised as important causes of CAP both in children and adults. Viral pneumonia account for 13 - 50% of single pathogen diagnosed community-acquired pneumonia cases and 8 -27% of mixed bacterial-viral pneumonia.
Viral Pneumonia
Bacterial pneumonia
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Aim. To investigate the aetiology of community-acquired pneumonia in hospitalised children and to evaluate the accuracy of the methods for its laboratory confirmation. Materials and Methods. We performed descriptive and cross-sectional epidemiological studies. Results of the rapid immunochromatographic assay (ICT) were compared with those obtained by polymerase chain reaction (PCR). Results. DNA of Streptococcus pneumoniae and Mycoplasma pneumoniae was found in 65.5% and 13.8% of the patients. Microbial associations were observed in 13.7% of patients (Mycoplasma pneumoniae + Streptococcus pneumoniae, 10.3%; Streptococcus pneumoniae + Haemophilus influenzae, 3.4%). Chlamydophila pneumoniae and SARS-CoV-2 were not detected. The cause of community-acquired pneumonia was not identified in 6.9% of the cases. A diagnostic accuracy of ICT was 27.58% and its sensitivity was relatively small (9.09%; 95% CI 1; 29), compared with a relatively high specificity (85.7%; 95% CI 42; 100). Conclusions. Rapid ICT assay must be accompanied by the PCR or other diagnostic methods for the diagnosis of pneumococcal community-acquired pneumonia in children.
Chlamydophila pneumoniae
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The isolation rate of Streptococcus pneumoniae in sputum cultures from patients with pneumococcal pneumonia is low. An investigation was made to determine whether this low yield might be due to loss of pneumocci and/or overgrowth by pharyngeal flora before the specimen is plated. Pneumococcal survival times and pharyngeal overgrowth at 4 degrees C and at room temperature were determined in sputum obtained from 42 patients with pneumococcal pneumonia. It was found that pneumococci survived for long periods in sputum--2.2 +/- 1.4 days at room temperature and 9.5 +/- 3.6 days at 4 degrees C. Overgrowth by pharyngeal flora occurred in only 6 of 42 specimens kept at 4 degrees C and 31 of 42 specimens kept at room temperature. The low yield of S. pneumoniae in sputum from patients with pneumococcal pneumonia is not explained by decreased viability of the organism.
Pneumococcal pneumonia
Pneumococcal infections
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