Effect of clinical spectrum, inoculum size and physician characteristics on sensitivity of a rapid antigen detection test for group A streptococcal pharyngitis

We aimed to assess the independent effect of clinical spectrum, bacterial inoculum size and physician characteristics on the sensitivity of a rapid antigen detection test (RADT) for group A streptococcus (GAS) in children. Double throat swabs were collected from 1,482 children with pharyngitis and 294 asymptomatic children in a French prospective, office-based, multicenter (n?=?17) study, from October 2009 to May 2011. Patient- and physician-level factors potentially affecting RADT sensitivity were studied by univariate and multivariate multilevel analysis, with laboratory throat culture as the reference test. In children with pharyngitis and asymptomatic children, the prevalence of GAS was 38 % (95 % confidence interval 36–41 %) and 11 % (7–14 %), respectively. Overall, RADT sensitivity was 87 % (84–90 %). On stratified and multivariate multilevel analysis, RADT sensitivity was higher for children with pharyngitis than asymptomatic children (89 % vs. 41 %), children <9 than ≥9 years old (88 % vs. 79 %) and those with heavy than light inoculum (94 % vs. 53 %). RADT sensitivity was influenced by the physician performing the test (range 56–96 %, p?=?0.01) and was higher for physicians with hospital-based clinical activity in addition to office-based practice (adjusted odds ratio 3.4 [95 % confidence interval 1.9–6.3], p?<?0.001); inter-physician variations in RADT sensitivity were largely explained by this variable (proportional change in variance >99 %). The sensitivity of the RADT is independently affected by patient- and physician-level factors. Physicians who base their diagnosis of GAS pharyngitis on the results of a RADT alone should consider diagnostic accuracy monitoring and adequate training when needed.     

You Say that You Want a Molecular Revolution? Changing from the Group A Streptococcus Antigen and Culture Paradigm to Molecular Testing

Group A Streptococcus (GAS) (Streptococcus pyogenes) is the most common bacterial cause of acute pharyngitis. Diagnosed cases of GAS pharyngitis should be treated with antibiotics to prevent primary and secondary complications. Commonly, testing for GAS pharyngitis can be done rapidly (in minutes) using rapid antigen detection tests (RADTs), which generally have relatively high specificity (>90%) but lower sensitivity (70 to 90%). The low sensitivity of GAS RADTs requires that culture be performed to maximize sensitivity, which delays the final result by 24 to 48 hours. New molecular GAS assays are on the market and offer relatively rapid (i.e., minutes to tens of minutes) and highly sensitive results so that culture is not required for negative results. We describe our experience with moving from RADT and culture testing for GAS to solely molecular testing, providing quicker results for improved patient care.     

Vaccine hesitancy among general practitioners: evaluation and comparison of their immunisation practice for themselves,their patients and their children

To gain knowledge about vaccine hesitancy among general practitioners (GPs), we conducted a survey to compare their vaccination attitudes for themselves, their children and their patients. A questionnaire survey was sent to GPs working in private practice in the Rhône-Alpes region, France, between October 2013 and January 2014. GPs’ immunisation practices for diphtheria–tetanus–poliomyelitis (DTP), measles–mumps–rubella (MMR), pneumococcal, pertussis, hepatitis B (hepB), human papillomavirus (HPV), seasonal and H1N1 influenza and meningococcal C (menC) vaccines were considered. Divergence was defined by the presence of at least one different immunisation practice between their patients and their children. A total of 693 GPs answered the questionnaire. When considering all investigated vaccines, 45.7 % of divergence was found. Individually, divergence was highest for the newest and more controversial, i.e. HPV (11.8 %), hepB (13.1 %), menC (23.7 %) and pneumococcal (19.8 %) vaccines. Only 73.9 % of GPs declared that they recommended HPV vaccine for their daughters. After multivariate analysis, older age was associated with higher risk of divergence. According to the French 2012 recommendations, GPs were insufficiently immunised, with 88 % for DTP and 72 % for pertussis. GPs declared to recommend vaccination against DTP, pertussis and MMR for their patients and their children in more than 95 % of cases. The declared rates of recommendation were lower than 90 % for other vaccines. These results bring new insight about vaccine hesitancy. GPs have divergent immunisation attitudes toward their relatives and their patients, especially when considering the newest and most controversial vaccines, with HPV vaccine being the main focus of controversies.     

Molecular and Clinical Diagnosis of Group A Streptococcal Pharyngitis in Children

Group A Streptococcus (GAS) pharyngitis is a very common condition causing significant morbidity in children. Accurate diagnosis followed by appropriate antimicrobial therapy is recommended to prevent postinfectious sequelae. Diagnosis of GAS pharyngitis by a rapid antigen detection test (RADT) or culture in the absence of discriminating clinical findings remains challenging. Validation of new sensitive rapid diagnostic tests is therefore a priority. The performance of a loop-mediated isothermal amplification (LAMP) assay (illumigene assay) for the diagnosis of GAS pharyngitis was compared with that of a RADT and standard culture in 361 pediatric throat swab samples. Discrepant results were resolved using an alternate molecular assay. Test results were correlated with clinical presentations in patients positive by either method. The closest estimate of the true prevalence of GAS pharyngitis was 19.7% (71/361 samples). The illumigene assay alone detected 70/71 GAS-positive samples; RADT and culture detected 35/71 and 55/71 samples, respectively. RADT followed by culture confirmation of RADT-negative specimens detected 58/71 cases. The illumigene assay increased identification among children eligible for testing by American College of Physicians (ACP)/American Academy of Family Physicians (AAFP) criteria from 31 to 39 positive cases, five of which were false positives. Analysis of clinical data in GAS-positive patients indicated that a significantly greater proportion of children with McIsaac scores of ≥4 tested positive by the illumigene assay versus RADT and culture. Overall, the illumigene assay was much more sensitive and was similarly specific for GAS detection, compared to culture alone, RADT alone, or the ACP/AAFP RADT/culture algorithm. Combining high sensitivity with rapidly available results, the illumigene GAS assay is an appropriate alternative to culture for the laboratory diagnosis of GAS pharyngitis in patients for whom testing is clinically indicated.     

Rapid diagnosis of pharyngitis caused by group A streptococci

Although commercial rapid antigen detection tests (RADTs) are more expensive than blood agar plate (BAP) cultures, the advantage they offer is the speed with which they provide results. Rapid identification and consequent prompt treatment of patients with pharyngitis due to group A beta-hemolytic streptococci (GABHS) can reduce the risk of spread of GABHS, can allow patients to return to school or work sooner, and may reduce the acute morbidity of this illness. In most studies, RADTs have been compared with BAP cultures as the criterion standard. However, these comparisons are complicated by the fact that there is no universally accepted procedure for performing a BAP culture. The great majority of the RADTs that are currently available have a high specificity (i.e., 95% or greater) and a sensitivity of between 70 and 90% compared with BAP cultures. Few published studies have compared the performance of various RADTs to each other or examined the performance of various RADTs in the office setting. There is also relatively little published information about how physicians in practice actually use RADTs, but the available information suggests that many physicians do not follow recommended guidelines. While the development of easy-to-perform RADTs for the diagnosis of GABHS pharyngitis has altered clinical practice substantially, only limited data about cost-effectiveness are currently available.     

Impact of technical training on rapid antigen detection tests (RADT) in group A streptococcal tonsillopharyngitis

Rapid antigen detection tests (RADT) are widely used for the rapid diagnosis of group A streptococcal (GAS) tonsillopharyngitis. In a prospective 3-year study, the reliability of two different RADT methods was compared, as performed by lab technicians versus physicians. Sensitivity and specificity, as well as positive and negative predictive values, were calculated. When performed by physicians, the results (44.4 %, 8.3 %, 26.7 % and 16.7 %) of a latex agglutination test (LAT) were unacceptably low. However, after switching to a lateral-flow immunoassay (LFIT) and implementing additional hands-on training, the performance improved dramatically (100 %, 92.6 %, 84.6 % and 100 %). In conclusion, technical errors, along with a lack of experience and expertise, negatively impact RADT accuracy.     

Diagnostic accuracy of rapid nucleic acid tests for group A streptococcal pharyngitis: systematic review and meta-analysis

BackgroundAcute pharyngitis is one of the most common conditions in outpatient settings and an important source of inappropriate antibiotic prescribing. Rapid antigen detection tests (RADTs) offer diagnosis of group A streptococcus at the point of care but have limited sensitivity. Rapid nucleic acid tests (RNATs) are now available; a systematic review of their accuracy is lacking.ObjectivesTo evaluate the accuracy of RNATs in patients with pharyngitis; to explore test-level and study-level factors that could explain variability in accuracy; and to compare the accuracy of RNATs with that of RADTs.Data sourcesMEDLINE, Embase, Web of Science (1990–2020).Study eligibility criteriaCross-sectional studies and randomized trials.ParticipantsPatients with pharyngitis.Index test/s and reference standardsRNAT commercial kits compared with throat culture.MethodsWe assessed risk of bias and applicability using QUADAS-2. We performed meta-analysis of sensitivity and specificity using the bivariate random-effects model. Variability was explored by subgroup analyses and meta-regression.ResultsWe included 38 studies (46 test evaluations; 17 411 test results). RNATs were most often performed in a laboratory. The overall methodological quality of primary studies was uncertain because of incomplete reporting. RNATs had a summary sensitivity of 97.5% (95% CI 96.2%–98.3%) and a summary specificity of 95.1% (95% CI 93.6%–96.3%). There was low variability in estimates across studies. Variability in sensitivity and specificity was partially explained by test type (p < 0.05 for both). Sensitivity analyses limited to studies with low risk of bias showed robust accuracy estimates. RNATs were more sensitive than RADTs (13 studies; 96.8% versus 82.3%, p 0.004); there was no difference in specificity (p 0.92).ConclusionsThe high diagnostic accuracy of RNATs may allow their use as stand-alone tests to diagnose group A streptococcus pharyngitis. Based on direct comparisons, RNATs have greater sensitivity than RADTs and equal specificity. Further studies should evaluate RNATs in point-of-care settings.     

Antibiotic use in children is not influenced by the result of rapid antigen detection test for the respiratory syncytial virus.

BACKGROUND: Rapid antigen detection test (RADT) for respiratory syncytial virus (RSV) is widely used in children hospitalized with acute respiratory tract infection (ARTI), but its influence on antibiotic (AB) use is uncertain. OBJECTIVE: To evaluate if confirmation of RSV infection by RADT modified AB use and elucidate others factors associated with the continuation of antibiotics. STUDY DESIGN: Charts of children hospitalized with viral ARTI aged 0-35 months were reviewed. Modification of antibiotics according to RSV RADT results was compared using Kaplan-Meier estimates and multivariate Cox regression. RESULTS: Of children receiving antibiotics when the RSV RADT result was available, RSV RADT was positive in 144 and negative in 54. Positive RSV RADT results did not lead to modification of antibiotic use. Factors independently associated with cessation of intravenous antibiotics were age > or = 3 months (HR 2.44 [1.41-4.21]) and absence of pneumonia (HR 1.50 [1.03-2.19]). Absence of otitis was associated with cessation of oral antibiotics (HR 9.16 [95% CI, 2.35-35.76]). CONCLUSION: Confirmed presence of RSV by RADT did not influence antibiotic use in young children with ARTI. Except with pneumonia, the risk of bacterial superinfection of RSV infected children is minimal and confirmation of RSV infection should prompt treating physicians to interrupt antibiotics.     

Improving diagnostic accuracy of bacterial pharyngitis by near patient measurement of C-reactive protein (CRP)

BACKGROUND: Sore throat or pharyngitis is an extremely prevalent condition in primary care. There is a diagnostic dilemma in differentiating bacterial and non-bacterial infections for adequate use of antibiotics. Standard diagnostic procedures take too long for an immediate decision. AIM: To evaluate, if near patient C-reactive protein measurement in the general practice surgery improves diagnostic accuracy. METHOD: One hundred and seventy-nine consecutive patients with sore throat, from 15 general practitioners (GPs) in southern Germany (phase 1) and 161 consecutive patients from 14 GPs (phase 2), were examined physically and a throat-swab was taken and white blood-cell count (WBC) and CRP-measurement were performed. In phase 1, CRP was measured centrally to assess the method's diagnostic value and the adequate threshold. In the second phase, near patient CRP was measured and CRP values were used to make a diagnosis. RESULTS: Using relative operating characteristics (ROC) analysis, the diagnostic value of CRP measurement was much better than WBC count (area under curve = 0.85 versus 0.68). All diagnostic parameters improved when using the near patient CRP measurement. Sensitivity went up from 0.61 (95% confidence interval = 0.45-0.75) to 0.78 (0.61-0.90), specificity went up from 0.73 (0.65-0.81) to 0.82 (0.73-0.88). Positive and negative predictive value improved significantly as well. Diagnostic accuracy went up from 70.1% to 81.0%. Out of 1000 theoretical patients with sore throat, 109 more will be treated correctly when using CRP measurement as a diagnostic tool. CONCLUSIONS: Use of near patient CRP measurement can improve diagnostic accuracy in the differentiation of bacterial and non-bacterial pharyngitis in primary care, and potentially results in a more adequate use of antibiotics.     

GPs' awareness of patients' preference for place of death

Background

Being able to die in one''s place of choice is an indicator of the quality of end-of-life care. GPs may play a key role in exploring and honouring patients'' preferences for place of death.

Aim

To examine how often GPs are informed about patients'' preferred place of death, by whom and for which patients, and to study the expressed preferred place of death and how often patients die at their preferred place.

Design of study

One-year nationwide mortality retrospective study.

Setting

Sentinel Network of GPs in Belgium, 2006.

Method

GPs'' weekly registration of all deaths (patients aged ≥1 year).

Results

A total of 798 non-sudden deaths were reported. GPs were informed of patients'' preferred place of death in 46% of cases. GPs obtained this information directly from patients in 63%. GP awareness was positively associated with patients not being hospitalised in the last 3 months of life (odds ratio [OR] = 3.9; 95% confidence interval [CI] = 2.8 to 5.6), involvement of informal caregivers (OR = 3.3; 95% CI = 1.8 to 6.1), use of a multidisciplinary palliative care team (OR = 2.5; 95% CI = 1.8 to 3.5), and with presence of more than seven contacts between GP and patient or family in the last 3 months of life (OR = 3.0; 95% CI = 2.2 to 4.3). In instances where GPs were informed, more than half of patients (58%) preferred to die at home. Overall, 80% of patients died at their preferred place.

Conclusion

GPs are often unaware of their patients'' preference for place of death. However, if GPs are informed, patients often die at their preferred location. Several healthcare characteristics might contribute to this and to a higher level of GP awareness.     

Risk factors and pathogens involved in early ventilator-acquired pneumonia in patients with severe subarachnoid hemorrhage

Ventilator-acquired pneumonia (VAP) is a common burden in intensive care unit (ICU) patients, but, to date, specific data are not available in patients with severe aneurysmal subarachnoid hemorrhage (SAH). A single neuro-ICU retrospective analysis of 193 patients with SAH requiring mechanical ventilation (MV) ≥48 h admitted from January 2005 to May 2010 was undertaken. The diagnosis of early VAP was prospectively upheld during a multidisciplinary staff meeting, according to the American Thoracic Society (ATS) 2005 guidelines with a threshold of 7 days after the onset of MV. Patients had a median age of 53 (44–62) years and 70 (36 %) were male. The median Glasgow coma scale (GCS) score before MV was 9 (5–14). 142 (74 %) patients had a World Federation of Neurosurgeons (WFNS) score?≥III. Aneurysm was secured with an endovascular coiling procedure in 162 (84 %) patients. 81 (48.7 %) patients declared an early VAP. On multivariate analysis, male sex (odds ratio [OR] 2.26, 95 % confidence interval [CI] [1.14–4.46]), use of mannitol before day 7 (OR 3.03, 95 % CI [1.54–5.95]), and achieving enteral nutrition ≥20 kcal kg^?1 day^?1 after day 7 (OR 2.91, 95 % CI [1.27–6.67]) remained independent risk factors of VAP. The main pathogens involved were methicillin-susceptible Staphylococcus aureus (MSSA) (34.9 %), Haemophilus influenzae (28.1 %), Streptococcus pneumoniae (15.5 %), and Enterobacteriaceae (10.7 %). Early VAP was associated with a longer duration of MV and ICU stay, but not with an excess of mortality. Early VAP bears significant morbidity in patients with severe SAH. Pathogens involved in early VAP are susceptible to antibiotics. Among modifiable risk factors of VAP, early enteral nutrition could be an easy and effective target.