Rapid Streptococcal Antigen Detection Test Research Articles

Use of McIsaac Scoring and Rapid Streptococcal Antigen Detection Test for Diagnosis of Group A Streptococcal Pharyngitis in Children

Use of McIsaac Scoring and Rapid Streptococcal Antigen Detection Test for Diagnosis of Group A Streptococcal Pharyngitis in Children

Point-of-care testing and antibiotics prescribing in out-of-hours general practice: a register-based study in Denmark

BackgroundPoint-of-care testing may reduce diagnostic uncertainty in case of suspicion of bacterial infection, thereby contributing to prudent antibiotic prescribing. We aimed to study variations in the use of point-of-care tests (C-reactive protein test, rapid streptococcal antigen detection test, and urine dipstick) among general practitioners (GPs) and the potential association between point-of-care testing and antibiotic prescribing in out-of-hours general practice.MethodsWe conducted a population-based observational register-based study, based on patient contacts with out-of-hours general practice in the Central Denmark Region in 2014–2017. The tendency of GPs to use point-of-care testing was calculated, and the association between the use of point-of-care testing and antibiotic prescribing was evaluated with the use of binomial regression.ResultsOut-of-hours general practice conducted 794,220 clinic consultations from 2014 to 2017, of which 16.1% resulted in an antibiotic prescription. The GP variation in the use of point-of-care testing was largest for C-reactive protein tests, with an observed variation (p90/p10 ratio) of 3.0; this means that the GPs in the 90th percentile used C-reactive protein tests three times as often as the GPs in the 10th percentile. The observed variation was 2.1 for rapid streptococcal antigen detection tests and 1.9 for urine dipsticks. The GPs who tended to use more point-of-care tests prescribed significantly more antibiotics than the GPs who tended to use fewer point-of-care tests. The GPs in the upper quintile of the tendency to use C-reactive protein test prescribed 22% more antibiotics than the GPs in the lowest quintile (21% for rapid streptococcal antigen detection tests and 8% for urine dipsticks). Up through the quintiles, this effect exhibited a positive linear dose–response correlation.ConclusionThe GPs varied in use of point-of-care testing. The GPs who tended to perform more point-of-care testing prescribed more antibiotics compared with the GPs who tended to perform fewer of these tests.

Evaluation of Rapid Antigen Detection Test for Group A Streptococci Pharyngitis among Children in an Out-Patient Clinic in Malaysia

One of the most common conditions encountered in the out-patient setting is acute pharyngitis. Group A Streptococcus (GAS) accounts for 15%-30% of cases of sore throat particularly in children under 15 years old. Rapid antigen testing (RADT) is an alternative diagnostic method to detect GAS pharyngitis. This study was done to evaluate the agreement between RADT whereby BIONEXIA® Strep A Plus (BioMérieux, France) kit was used and throat culture in the diagnosis of GAS pharyngitis in children presented with a sore throat. One hundred and ten children from a primary health care clinic with sore throat were included in this study. All children were evaluated based on McIsaac scoring and throat swab samples were taken for both throat culture and RADT testing. The prevalence of GAS pharyngitis by RADT in this study was 7.3% over one year. A higher incidence of GAS pharyngitis was noted in the school-aged children than the preschool-age children. There was no correlation between cough, lymph node enlargement, and tonsillar enlargement in predicting GAS pharyngitis. The sensitivity and specificity of RADT were 100% and 98%, respectively, when taking throat culture as a gold standard. A good agreement between RADT and throat culture was achieved (k=0.848). McIsaac scoring was noted to have good predictability for GAS pharyngitis with AUC=0.82. In conclusion, the rapid streptococcal antigen detection test showed excellent sensitivity and specificity and detecting GAS from the throat swab samples. Thus, it can be used to aid in the diagnosis of group A Streptococcal pharyngitis and could reduce the overuse of antibiotics. McIsaac score has also proven to be useful as a screening tool for bacterial pharyngitis.

2179. Detection of Group A Streptococcus in the Saliva of Children Presenting With Pharyngitis Using the cobas®LIAT® PCR System

BackgroundCLIA waived polymerase chain reaction (PCR) has recently become available as a point of care test for Group A Streptococci (GAS) in individuals presenting with pharyngitis, enabling rapid and accurate diagnosis. However, swabbing the pharynx results in discomfort and is often dreaded by young children which may result in poor quality sampling.ObjectiveIn order to assess the viability of saliva as a sample specimen for GAS, this study compared saliva samples with pharynx swabs of children with sore throat, using swabs inoculated by children sucking on them as they would a lollipop in the context of newly available very sensitive techniques.MethodsWe enrolled children ages 5–15 years presenting with sore throat and known to have a positive rapid streptococcal antigen detection test (RADT) performed on a posterior pharyngeal swab, at the discretion of the primary care provider. The RADT used was the SureVue® (Fisher Scientific) system. A second swab was obtained by having the child suck on the swab in the anterior mouth for 30 seconds and a third swab was obtained from the posterior pharynx. PCR was performed on these two additional swabs using the cobas®LIAT® (Roche) system according to the manufacturer’s instructions.ResultsSeventeen children were enrolled in the study between January and April 2019. The mean age of enrollment was 9.6 years (range 6–15). By design all children were known to have a positive RADT for GAS. The LIAT posterior pharynx swab was positive in all 17 subjects. In addition, the LIAT saliva swab was positive in all 17 subjects.ConclusionIn this small pilot study, there was 100% concordance between the RADT for GAS and both the posterior pharyngeal and saliva swab using the cobas®LIAT® PCR system. Performing saliva swabs will result in less discomfort and distress to children who are tested for GAS. Further study is needed to determine the sensitivity and specificity of saliva swabs for the detection of GAS in children presenting with acute pharyngitis.Disclosures All authors: No reported disclosures.

853. Epidemiology of Groups A, C, and G β-Hemolytic Streptococcal Pharyngitis

BackgroundTreatment of Group A Streptococcus (GAS) pharyngitis is imperative to mitigate sequelae such as rheumatic heart disease. The need for treatment of Group C Streptococcus (GCS) and Group G Streptococcus (GGS) pharyngitis is unclear, as rheumatogenic sequelae have not been well documented. Our institution switched from culture to molecular confirmation testing for a negative rapid streptococcal antigen detection test. Cultures reported GAS whereas molecular testing reported GAS, GCS, and GGS. We performed a retrospective chart review to examine the epidemiological differences of GAS, GCS, and GGS pharyngitis.MethodsRecords were obtained of pharyngeal samples from patients sent for testing at Beaumont Health Laboratory. In all, 92,369 records were analyzed. There were 47,106 records of cultures from May 2012 through December 2014 and 45,263 records of molecular testing from May 2015 to December 2017. Samples positive for either GCS or GGS were reported as positive for Group CG Streptococcus (GCGS). Epidemiological factors were evaluated. If available, electronic records from GCGS positive samples were evaluated for clinical features, antibiotics used, and sequelae or complications reported.ResultsMolecular testing showed GAS positivity of 9.3% (n = 4,189) and GCGS positivity of 1.5% (n = 687). GCGS pharyngitis was more likely during the summer months and in young adults 13 years and older than children under 13 years. GAS pharyngitis was more likely during spring months and in children aged 4–9 years. Mean age of GCGS pharyngitis was 13 vs. 8.6 years for GAS pharyngitis. Similar results were obtained for GAS between culture and molecular testing records. Amoxicillin was most often prescribed for treatment of GCGS. There were few instances of severe GCGS exudative or recurrent pharyngitis that required hospitalization or tonsillectomy. There were no cases of rheumatic fever or rheumatic heart disease associated with GCGS.ConclusionThis is the largest study based on our literature review to evaluate the epidemiology of GAS, GCS, and GGS pharyngitis in children and adults. We found a seasonal and age difference between GAS and GCGS. Complications were rare, and no rheumatogenic sequelae were noted from GCGS infections. Disclosures All Authors: No reported Disclosures.

Use of Streptococcal Tonsillopharyngitis Diagnostic Tests in Children

Objectives Group A β hemolytic streptococcus (GABHS) is the main bacterial case of tonsillopharyngitis in children, but most cases of tonsillopharyngitis are viral. Rapid diagnosis and early antibiotherapy of GABHS infections are important to help prevent suppurative and nonsuppurative complications. This retrospective study investigated the using of the rapid streptococcal antigen detection test and traditional throat culture in diagnosing tonsillopharyngitis in children. Materials and Methods Retrospectively, the laboratory results of throat culture and rapid strep A test (optic immunoassay) of 1,654 children were compared. Results Of the 1,654 subjects, the rapid test was performed in 1,110 (67.1%), and throat culture was performed in 930 (56.2%). Both tests were performed in 479 (31.1%) patients and the correlation between the tests was 87.2%. The power of the correlation between the two tests was 0.6 ( p Conclusion The rapid strep A testing is more practical and quick to detect GABHS. This can be an important strategy to reduce unnecessary antibiotic use. Throat culture should be used to confirm the negative findings of the rapid test.

Comparison of Clinical Findings and Rapid Streptococcal Antigen Detection Test in the Diagnosis of Group A Streptococcal (GAS) Pharyngitis

Background: Group A -hemolytic Streptococcal (GAS) pharyngitis is a common illness in children. Diagnosis and proper treatment of group A streptococcal sore throat is important particularly to prevent non-superlative sequel. Clinical findings continue to be used in differentiating streptococcal infection from viral sore throat. Objectives: The aim of this study was to evaluate the accuracy of clinical findings and rapid test in comparison with culture in the diagnosis of group A Streptococcal (GAS) pharyngitis. Patients and Methods: Ninety-four children between 3 to 16 years, who were referred to the pediatric clinic of Rasoul-e-Akram hospital with clinical findings of fever or sore throat were evaluated from October 2006 to May 2007. Clinical findings were recorded and swabs were taken for group A streptococcal cultures and streptococcal rapid antigen detection test. Analysis of statistical significance was performed using the chi-square method. The accuracy of clinical findings and rapid test was compared with the culture method as the gold standard, and sensitivity, specificity, positive predictive values, negative predictive value, positive likelihood ratio (LR+) and negative likelihood ratio (LR-) were calculated. Results: The culture was positive in 38 (40.4%) of the 94 evaluated children. The mean age of children was 8 3.7 years. The presence of petechiae, exudate and Lymphadenopathy (LAP) was more likely in children with positive streptococcus culture and rapid test (P value < 0.05). Lymphadenopathy was known to feature the most sensitivity (100%), specificity (76.8%), and positive predictive value (74.5%), negative predictive value (100%) and positive likelihood ratio (LR) (4.3) among clinical findings. The results of rapid test showed sensitivity of 89.4%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 93.3% in comparison with culture as the gold standard. In general, the accuracy of rapid test was found higher than subjective clinical findings (P = 0.001). Conclusions: Although LAP had good performance in early diagnosis of GAS, a combination of clinical findings, including tonsillar exudates, petechiae with results of rapid antigen test or culture is necessary for clinician judgment. Throat culture is the gold standard test for detecting group A Streptococcal infection, but rapid test is a good replacement for culture.

Clinical score and rapid antigen detection test to guide antibiotic use for sore throats: randomised controlled trial of PRISM (primary care streptococcal management)

The paper Abstract Objective To determine the effect of clinical scores that predict streptococcal infection or rapid streptococcal antigen detection tests compared with delayed antibiotic prescribing. Design Open adaptive pragmatic parallel group randomised controlled trial. Setting Primary care in United Kingdom. Patients Patients aged ≥3 with acute sore throat. Intervention An internet programme randomised patients to targeted antibiotic use according to: delayed antibiotics (the comparator group for analyses), clinical score, or antigen test used according to clinical score. During the trial a preliminary streptococcal score (score 1, n=1129) was replaced by a more consistent score (score 2, n=631; features: fever during previous 24 hours; purulence; attends rapidly (within three days after onset of symptoms); inflamed tonsils; no cough/coryza (acronym FeverPAIN). Outcomes Symptom severity reported by patients on a 7 point Likert scale (mean severity of sore throat/difficulty swallowing for days two to four after the consultation (primary outcome)), duration of symptoms, use of antibiotics. Results For score 1 there were no significant differences between groups. For score 2, symptom severity was documented in 80% (168/207 (81%) in delayed antibiotics group; 168/211 (80%) in clinical score group; 166/213 (78%) in antigen test group). Reported severity of symptoms was lower in the clinical score group (−0.33, 95% confidence interval −0.64 to −0.02; P=0.04), equivalent to one in three rating sore throat a slight versus moderate problem, with a similar reduction for the antigen test group (−0.30, −0.61 to −0.00; P=0.05). Symptoms rated moderately bad or worse resolved significantly faster in the clinical score group (hazard ratio 1.30, 95% confidence interval 1.03 to 1.63) but not the antigen test group …

Clinical score and rapid antigen detection test to guide antibiotic use for sore throats: randomised controlled trial of PRISM (primary care streptococcal management)

Objective To determine the effect of clinical scores that predict streptococcal infection or rapid streptococcal antigen detection tests compared with delayed antibiotic prescribing.Design Open adaptive pragmatic parallel group randomised controlled...

A qualitative study of GP, NP and patient views about the use of rapid streptococcal antigen detection tests (RADTs) in primary care: ‘swamped with sore throats?’

ObjectiveTo explore patient and healthcare professionals’ (HCP) views of clinical scores and rapid streptococcal antigen detection tests (RADTs) for acute sore throat.DesignQualitative semistructured interview study.SettingUK primary care.ParticipantsGeneral practitioners (GPs), nurse...

Papel do teste de detecção rápida do antígeno do estreptococcus beta-hemolítico do grupo a em pacientes com faringoamigdalites

O Streptococcus beta-hemolítico do grupo A (SGA) é o agente etiológico mais comum das faringoamigdalites (FA). O diagnóstico etiológico correto e tratamento adequado evitam complicações supurativas e não-supurativas da faringoamigdalite estreptocócica, entretanto, métodos clínicos de diagnóstico não são confiáveis. Os métodos rápidos de detecção do antígeno do SGA podem ser utilizados no diagnóstico deste agente e evitar uso indevido de antibióticos. OBJETIVOS: Os autores objetivaram avaliar a sensibilidade e especificidade dos testes rápidos para detecção do antígeno do SGA em nosso meio. FORMA DE ESTUDO: Clínico prospectivo. METODOLOGIA: Oitenta e um pacientes com faringoamigdalite aguda, atendidos no PS-ORL do Hospital das Clínicas da FMUSP, no período de maio de 2001 a abril de 2002, foram submetidos a duas coletas simultâneas de material de orofaringe com swabs. O teste rápido de detecção do SGA foi confrontado com a cultura em placa agar-sangue ("gold standard" para o diagnóstico etiológico). RESULTADOS: De 81 pacientes, 56% tiveram teste rápido positivo e 44% negativo; 40.7% apresentaram crescimento de SGA na cultura; a sensibilidade e especificidade do teste rápido foram, respectivamente, 93,9% e 68,7%. O valor preditivo negativo e positivo foram, respectivamente, 94,2% e 67,4%. CONCLUSÕES: A alta sensibilidade do exame permite utilizá-lo com intuito de identificar pacientes com SGA. Os testes de detecção rápida do antígeno estreptocócico se mostraram uma importante arma coadjuvante no diagnóstico etiológico das faringoamigdalites.

Role of rapid antigen detection test for the diagnosis of group-A ß-hemolytic streptococcus in patients with pharyngotonsillitis

SummaryGroup A ß-hemolytic streptococcus (GAS) is an important pharyngotonsillitis etiologic agent. Correct etiologic diagnosis and early treatment prevent suppurative and non-suppurative complications of streptococcal pharyngotonsillitis, however, clinical diagnostic methods are not reliable. Within this context, rapid detection methods of GAS antigen are useful to diagnose this agent.AimThe objective of the present study was to determine the sensitivity and specificity of rapid GAS antigen detection tests used in Brazil.Study DesignClinical prospective.MethodsEighty-one patients with clinical diagnosis of acute pharyngotonsillitis seen at the otorhinolaryngology emergency department of University Hospital, FMUSP, between May 2001 and April 2002, were submitted to two simultaneous collections of oropharyngeal material using swabs. Rapid GAS antigen detection test was compared to culture on blood agar, the gold standard for the diagnosis of this etiologic agent.ResultsAmong the 81 studied patients, the rapid test was positive in 56% and negative in 44%. GAS growth in culture was observed for 40.7% of the patients. The sensitivity and specificity of the rapid test were, respectively, 93.9% and 68.7%, and the negative and positive predictive values were 94.2 and 67.4%, respectively.ConclusionsWe concluded that the high sensitivity of the test permits its use for the identification of patients with GAS. Rapid streptococcal antigen detection tests have been shown to be an important supporting tool in the etiologic diagnosis of pharyngotonsillitis.

Role of rapid antigen detection test for the diagnosis of group A beta-hemolytic streptococcus in patients with pharyngotonsillitis

SummaryGroup A β -hemolytic streptococcus (GAS) is an important pharyngotonsillitis etiologic agent. Correct etiologic diagnosis and early treatment prevent suppurative and non-suppurative complications of streptococcal pharyngotonsillitis; however, clinical diagnosis is not reliable. Within this context, rapid detection methods of GAS antigen are useful to diagnose this agent.AimThe objective of the present study was to determine sensitivity and specificity of rapid GAS antigen detection tests used in Brazil.Study designClinical prospective. Method: Eighty-one patients with clinical diagnosis of acute pharyngotonsillitis seen at the otorhinolaryngology emergency department of the University Hospital, FMUSP, between May 2001 and April 2002 were submitted to two simultaneous collections of oropharyngeal material using swabs. The rapid GAS antigen detection test was compared to culture on blood agar, the gold standard for the diagnosis of this etiologic agent.ResultsAmong the 81 patients studied, the rapid test was positive in 56% and negative in 44%. GAS growth in culture was observed in 40.7% of the patients. Sensitivity and specificity of the rapid test were, respectively, 93.9% and 68.7%, and the negative and positive predictive values were 94.2 and 67.4%, respectively. Conclusions: We concluded that high sensitivity of the test allows its use in the identification of patients with GAS. Rapid streptococcal antigen detection tests have been shown to be an important adjuvant tool in the etiologic diagnosis of pharyngotonsillitis.

Oral dexamethasone for the treatment of pain in children with acute pharyngitis: A randomized, double-blind, placebo-controlled trial

Study objective: We compare oral dexamethasone with placebo for the relief of pain in children with acute pharyngitis. Methods: We performed a prospective, randomized, double-blind, placebo-controlled trial of children aged 5 to 16 years who presented to the emergency department with acute pharyngitis. Children rated their pain on a standardized color analog scale and had a rapid streptococcal antigen detection test performed to determine group assignment. Children were randomized to dexamethasone (0.6 mg/kg, maximum dose 10 mg) or placebo. Blinded research assistants called all families daily to determine pain scores until the point of complete pain relief. The primary outcome measures were the time to clinically significant pain relief and the time to complete pain relief. Results: A total of 184 children were enrolled in the study. There were 85 children in the antigen-positive group, of whom 45 were randomized to dexamethasone and 40 to placebo. In children with group A β-hemolytic streptococcal pharyngitis, the median time to clinically significant pain relief was 6 hours in the dexamethasone group versus 11.5 hours in the placebo group (P =.02; effect size of 5.5 hours with 95% confidence interval [CI] of 1.0 and 10.0 hours), and the time to complete pain relief was similar (36 hours for placebo versus 40 hours for dexamethasone, P =.86; effect size of 4.0 hours with 95% CI of −9.3 and 17.3 hours) in the placebo group. There were 99 children enrolled in the antigen-negative group, of whom 47 received dexamethasone and 52 received placebo. In this group, the median time to clinically significant pain relief was 13 hours in the dexamethasone group versus 9 hours in the placebo group (P =.32; effect size of 4 hours with 95% CI of −2 and 10 hours), and the time to complete pain relief was similar (48 hours for placebo versus 50 hours for dexamethasone, P =.61; effect size of 2 hours with 95% CI of −11.8 and 15.8 hours). Conclusion: For all children with acute pharyngitis, oral dexamethasone does not decrease the time to onset of clinically significant pain relief or time to complete pain relief. However, in the subset of children with positive antigen detection test results, there is a statistically significant improvement in time to onset of pain relief, but it is of marginal clinical importance. [Ann Emerg Med. 2003;41:601-608.]

Comparison of an immunochromatographic method for rapid identification of group A streptococcal antigen with culture method

To compare the sensitivity and specificity of Concise Strep A (Hybritech, San Diego, Calif), an immunochromatographic group A streptococcal rapid antigen detection system, with a two-plate culture method for the diagnosis of streptococcal pharyngitis, and to evaluate the need for routine back-up culture when this rapid test is used. Throat cultures were obtained from 351 children with acute pharyngitis by duplicate rayon-tipped swabs held in parallel and vigorously rubbed against both tonsils and the posterior pharyngeal wall. One swab was tested for group A streptococcal antigen by a registered licensed laboratory technologist in the pediatrician's office. The other swab was streaked over each of two sheep blood agar plates, one of which was enhanced with trimethoprim in combination with sulfamethoxazole. The plain sheep blood agar plate was then incubated in a candle-extinguish jar. The enhanced agar plate was placed in a gas-pack anaerobic jar. Both plates were incubated for up to 48 hours at 35 degrees C. A six-person group pediatric practice. Three hundred fifty-one children. The Concise Strep A antigen detection test produced 129 positive results. Only six of the 129 were not confirmed by culture method. There were four false-negative rapid streptococcal antigen detection test results, all of which were found after a single overnight incubation. The sensitivity for the Concise Strep A test was 96.9% and the specificity was 97.4%. The plain 5% sheep blood agar plate (without trimethoprim and sulfamethoxazole), which was incubated in a candle-extinguish jar, identified 123 (97%) of the 127 positive throat cultures. The second 24-hour incubation and use of trimethoprim and sulfamethoxazole agar were not rewarding for this study. Concise Strep A, a polyclonal antibody test, in conjunction with a color immunochromatographic assay for soluble streptococcal carbohydrate antigen A appears to be accurate, sensitive, and specific when throat swabs are carefully obtained and when qualified, licensed laboratory technologists perform the procedure. Further studies should be done to confirm our findings, especially when nurses or office staff perform the rapid test procedure in the office setting. If our findings are confirmed, the use of back-up cultures for negative rapid test results obtained using Concise Strep A would be unnecessary.

Evaluation of the throat culture as a follow-up for an initially negative enzyme immunosorbent assay rapid streptococcal antigen detection test.

In a study of the efficacy of following up an initially negative enzyme immunosorbent assay (EIA) rapid streptococcal antigen detection test with a throat culture, 2 double swabs (4 total) were obtained from 264 pediatric patients with sore throats. Although a throat culture was more specific (97%) than the EIA (89%), the sensitivity (87%) and negative predictive value (97%) of a single EIA was the same as that of a single throat culture. A follow-up throat culture was more accurate than a follow-up EIA. We conclude that the office EIA tested results in more false positives but misses no more true positives than a single throat culture processed by a well-controlled microbiology laboratory. If a follow-up technique is used for an initially negative EIA rapid streptococcal antigen detection test, the throat culture is the superior test and would be equally applicable following an initially negative throat culture or EIA.

An in vitro comparison of eight rapid streptococcal antigen detection tests

The last few years have seen a dramatic increase in the number of rapid antigen detection tests for patients with group A fl-hemolytic streptococcal pharyngitis. In general, most of the ADTs are specific enough, in comparison with the throat culture, that a positive ADT result can stand alone. A negative ADT result, however, in the opinion of most investigators, lacks adequate sensitivity to be used without a ,backup throat culture? 4 Because most clinical studies involve only one or two ADTs at a tim e, and because of the variety of clinical settings in which they are tested, few data exist with regard to the relative sensitivity of various ADTs tested in common settings and conditions. Moreover, it is virtually impossible to obtain meaningful comparative data from in viva sources, because no two throat swabs will yield the same number of organisms, even when obtained from the same source (Lewey S, White CB, Lieberman MM, Morales E: unpublished data). Thus we used a simple in vitro method to determine the relative sensitivity of eight commercially available rapid ADTs for the detection of serially diluted broth concentrations of GABHS.

Role of rapid tests for streptococcal pharyngitis in hospital infection control

Rapid streptococcal antigen detection tests are now an alternative to throat cultures for diagnosing group A streptococcal pharyngitis. Used alone, they are not suitable for hospital infection control applications because of the risk that individuals with streptococcal pharyngitis and a falsely negative test will spread the infection within the institution. However, a rapid test may be an economical method for screening employees with pharyngitis, provided that a throat culture is performed for everyone with a negative test. Compared with the use of throat cultures alone, this strategy reduces the number of missed diagnoses and the number of work days lost. Cost-benefit analysis shows that over a wide range of streptococcal prevalence and carrier rate the total cost is also less with the use of rapid tests first. If the prevalence of streptococcal pharyngitis is very low, the use of cultures alone is more cost-effective.