Chlamydia trachomatis samples testing falsely negative in the Aptima Combo 2 test in Finland, 2019.

Since February 2019, over 160 Chlamydia trachomatis (CT) cases testing negative or equivocal by Aptima Combo 2 (AC2) but positive by Aptima CT test run with Panther instruments occurred in Finland. The AC2 test targets chlamydial 23S rRNA while the CT test targets 16S rRNA. Sequencing of 10 strains revealed a nucleotide substitution in 23S rRNA. The significance of this for the failure of the AC2 test to detect the variant is not yet known.

PCR identification of bacteria in blood culture does not fit the daily workflow of a routine microbiology laboratory.

We have evaluated the GenoType blood culture assay (Hain Lifescience, Nehren, Germany) for the identification of bacteria in 233 positive blood cultures and assessed its suitability in the workflow of a routine microbiology laboratory. In 68/233 (29.2%) samples, the culture result could not be confirmed by the GenoType assay due to a lack of primers in the test, multiple organisms in the sample, or inconsistency with respect to the identification by culture. Although the GenoType blood culture assay gives satisfactory results for bacteria for which primers are available, there are difficulties in applying the test in the routine microbiology laboratory.

Screening of urine samples by flow cytometry reduces the need for culture.

Urine samples constitute a large proportion of samples tested in clinical microbiology laboratories. Culturing of the samples is fairly time- and labor-consuming, and most of the samples will yield no growth or insignificant growth. We analyzed the feasibility of the flow cytometry-based UF-500i instrument (Sysmex, Japan) to screen out urine samples with no growth or insignificant growth and reduce the number of samples to be cultured. A total of 1,094 urine specimens sent to our laboratory for culture during 4 months in the spring of 2009 in Lahti, Finland, were included in the study. After culture, all samples were analyzed with the Sysmex UF-500i for bacterial and leukocyte (white blood cell [WBC]) counts. Youden index and closest (0,1) methods were used to determine the cutoff values for bacterial and WBC counts in culture-positive and -negative groups. By flow cytometry, samples considered positive for UTI in culture had bacterial and WBC values that were significantly higher than those for samples considered negative. The flow cytometric screening worked best when both bacterial counts and WBC counts were used with age- and gender-specific cutoff values for all patient groups, excluding patients with urological disease or anomaly. By use of these cutoff values, 5/167 (3.0%) of culture-positive samples were missed by UF-500i and the percentage of samples that did not need to be cultured was 64.5%. Use of the UF-500i instrument is a reliable method for screening out a major part of the UTI-negative samples, significantly diminishing the amount of work required in the microbiology laboratory.

Yard vegetation is associated with gut microbiota composition.

Gut microbes play an essential role in the development and functioning of the human immune system. A disturbed gut microbiota composition is often associated with a number of health disorders including immune-mediated diseases. Differences in host characteristics such as ethnicity, living habit and diet have been used to explain differences in the gut microbiota composition in inter-continental comparison studies. As our previous studies imply that daily skin contact with organic gardening materials modify gut microflora, here we investigated the association between living environment and gut microbiota in a homogenous western population along an urban-rural gradient. We obtained stool samples from 48 native elderly Finns in province Häme in August and November 2015 and identified the bacterial phylotypes using 16S rRNA Illumina MiSeq sequencing. We assumed that yard vegetation and land cover classes surrounding homes explain the stool bacterial community in generalized linear mixed models. Diverse yard vegetation was associated with a reduced abundance of Clostridium sensu stricto and an increased abundance of Faecalibacterium and Prevotellaceae. The abundance of Bacteroides was positively and strongly associated with the built environment. Exclusion of animal owners did not alter the main associations. These results suggest that diverse vegetation around homes is associated with health-related changes in gut microbiota composition. Manipulation of the garden diversity, possibly jointly with urban planning, is a promising candidate for future intervention studies that aim to maintain gut homeostasis.

Connection between trimethoprim-sulfamethoxazole use and resistance in Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis.

The association between trimethoprim-sulfamethoxazole use and resistance among the major respiratory tract pathogens was investigated by comparing regional consumption of the drug to regional resistance in the following year in 21 central hospital districts in Finland. A total of 23,530 Streptococcus pneumoniae isolates, 28,320 Haemophilus influenzae isolates, and 14,138 Moraxella catarrhalis isolates were tested for trimethoprim-sulfamethoxazole susceptibility during the study period (1998-2004). Among the S. pneumoniae isolates, a statistically significant connection was found between regional consumption and resistance. No statistically significant connection was found between regional trimethoprim-sulfamethoxazole use and resistance among H. influenzae and M. catarrhalis isolates. According to our results, it seems that only in pneumococci can the development of trimethoprim-sulfamethoxazole resistance be influenced by restricting its use. However, trimethoprim-sulfamethoxazole remains an important antimicrobial agent because of its reasonable price. Hence, resistance to trimethoprim-sulfamethoxazole among these pathogens needs continuous monitoring.

Recommended and prescribed symptomatic treatment for acute maxillary sinusitis in Finnish primary care.

We studied the use of symptomatic medication in the treatment of acute maxillary sinusitis (AMS) in primary care and whether this use is in accordance with national guidelines. The data was collected annually in the Antimicrobial Treatment Strategies (MIKSTRA) Program in 30 primary health care centres throughout Finland during one week in November in the years from 1998 to 2002. Physicians and nurses collected the data about the diagnoses, prescription-only medicines and over the counter medicines prescribed or recommended for all patients with an infection during the study weeks. The MIKSTRA data comprised of 23.002 first consultations for an infection: 2.448 patients were diagnosed as having AMS. Altogether, 41% of them received some symptomatic medicine. Antihistamines with or without sympathomimetics were the most commonly prescribed or recommended symptomatic medicines (23% of the patients). For comparison, systemic antibacterial agents were prescribed for 93% of the AMS patients. We conclude that Finnish physicians recommend or prescribe more symptomatic medication without proven efficacy for AMS than recommended by the national guidelines. Especially, the use of antihistamines with or without sympathomimetics, mostly the combination of acrivastine and pseudoephedrine, was common although antihistamines were recommended only for patients with allergy or nasal polyps.

Analysis of the costs for the laboratory of flow cytometry screening of urine samples before culture.

Urine culture samples comprise a large proportion of the workload in clinical microbiology laboratories, and most of the urine samples show no growth or insignificant growth. A flow cytometry-based analyzer (Sysmex Corporation, Japan) has been used to screen out negative urine samples prior to culture in the Päijät-Häme district. We applied decision analytic modelling to analyze, from a laboratory perspective, the economic feasibility of the screening method as compared to culture only (conventional method) for diagnosis of urinary tract infection. Our model suggests that the least costly analytical strategy is the conventional method. The incremental cost of screening is €0.29/sample. Although laboratory costs are higher, considerable savings on workload can be achieved. Furthermore, screening has numerous benefits on the treatment process of a patient that well warrant the use of the screening method. We conclude that the incremental cost of screening the samples is worth the expense.

The Antimicrobial Treatment Strategies (MIKSTRA) program: a 5-year follow-up of infection-specific antibiotic use in primary health care and the effect of implementation of treatment guidelines.

BACKGROUND: A national 5-year follow-up study of infection-specific antibiotic use in primary care was conducted to see if prescribing practices change after implementing new treatment guidelines. METHODS: The data were collected during 1 week of November each year from 1998 to 2002 from 30 health care centers that covered a total population of 819,777 persons and in 2002 from 20 control health care centers that covered a population of 545,098 persons. National guidelines for 6 major infections (otitis media, sinusitis, throat infection, acute bronchitis, urinary tract infection, and bacterial skin infection) were published in 1999-2000. Multifaceted interventions were performed by local trainers teaching his or her coworkers, supported by feedback and patient and public information. RESULTS: The 6 infections targeted for intervention, together with unspecified upper respiratory tract infection constituted 80%-85% of all infections. The proportion of patients who received prescriptions for antibiotics did not change significantly. However, use of first-line antibiotics increased for all infections, and the change was significant for sinusitis (P<.001), acute bronchitis (P=.015), and urinary tract infections (P=.009). Also, the percentage of antibiotic treatments prescribed for the recommended duration increased significantly. Correct prescribing for respiratory tract infections improved by 6.4 percentage units (P<.001). However, there was no statistically significant difference in performance between study and control health care centers at follow-up. CONCLUSIONS: Moderate qualitative improvements in antibiotic use were observed after multifaceted intervention, but prescribing for unjustified indications, mainly acute bronchitis, did not decrease. Obtained infection-specific information on management of patients with infections in primary health care is an important basis for planning targeted interventions in the future.

Antimicrobial susceptibility testing of Streptococcus pneumoniae and Haemophilus influenzae --internal quality control as a quality tool on a national level.

Knowledge of the quality and conformity of antimicrobial resistance data is important for comparing resistance rates regionally and over time. In this study, we have evaluated these features of the Finnish national susceptibility surveillance data for two respiratory tract pathogens, Streptococcus pneumoniae and Haemophilus influenzae. For this purpose internal quality control results for two isolates (S. pneumoniae ATCC 49619 and H. influenzae ATCC 49247) were analyzed from 21 clinical microbiology laboratories over a 3-year period. The results show that standardization of the susceptibility testing methods has proceeded well. The number of protocols used for susceptibility testing has declined (from seventeen methods to two with S. pneumoniae and from eleven to three with H. influenzae) and the reproducibility is good. Nevertheless, we noticed that a few laboratories test and report susceptibility results without defined break-points and even include antimicrobials with questionable therapeutic effect. Another non-compliance with the standard was a lack of a regular control system to verify the attainment of the intended quality of results in some laboratories. Interlaboratory analysis of quality control results is a good way to evaluate the quality and conformity of national resistance data. Finnish laboratories have produced very reproducible and accurate susceptibility results in the pre-EUCAST period, which ended in 2011.

Implementing guidelines on acute maxillary sinusitis in general practice--a randomized controlled trial.

BACKGROUND: Management of acute maxillary sinusitis (AMS) is not optimal; antibiotics are often prescribed for viral sinusitis, which leads to many problems including those with antimicrobial resistance. Guidelines have been proposed as a means to change the professional practices. OBJECTIVE: Our aim was to study whether a nationwide guidelines implementation programme has an effect on the management of AMS in primary care. METHODS: A multi-centre randomized controlled trial was conducted in 30 health centres (HCs) covering a population of 819 777 people from 1998 to 2002. The participating HCs were randomized to implement guidelines either according to a problem-based learning (PBL) or an academic detailing (AD) method facilitated by local GPs. Data were gathered during 1 week in November in all study years and also from external control HCs in 2002. The main outcome measure was compliance with the key points of AMS management in national Current Care guidelines. RESULTS: Implementation of guidelines produced minor changes towards the recommended practices in the management of AMS. Use of the first-line drug amoxicillin increased slightly (from 39% to 48% in AD centres and from 33% to 45% in PBL centres, controls 40%). Proportion of courses of antibiotics with recommended duration increased in MIKSTRA study centres (from 34% to 40% in AD centres and from 32% to 47% in PBL centres, controls 43%). CONCLUSIONS: A nationwide guidelines implementation project produced modest changes in the management of AMS. There were no significant differences between AD and PBL education methods. Less than half the HCs were able to realize the project as intended, which decreases the internal validity of the study. The guidelines implementation might have benefited of more focussed targets and approaches that took into account the problems and practices of each HC.

Cost-effectiveness of implementing national guidelines in the treatment of acute otitis media in children.

OBJECTIVES: Acute otitis media (AOM) is one of the most common diseases of childhood, representing a major disease burden on the society. New evidence-based guidelines for AOM, focusing on children under 7 years of age, were introduced in Finland in 1999. The aim of this study was to evaluate the cost-effectiveness of implementing those guidelines in Finland. METHODS: A 5-year prospective trial was conducted in thirty community primary healthcare centers in Finland. All AOM patients between 0 and 6 years of age visiting the study health centers for the first time, for this episode of illness, during 1 week in November 1998 (n = 579) and November 2002 (n = 369) were included in this study. The outcome measure was the percentage of symptom-free patients. RESULTS: The mean direct cost of an AOM episode per patient stayed almost the same after implementing the guidelines, euro152 in 1998 and euro150 in 2002. After implementing the guidelines, the percentage of symptom-free patients was 10 percentage points higher than before the guidelines. The treatment after the implementation of the guidelines, thus, was a dominant strategy. CONCLUSIONS: Implementing the guidelines to the treatment of AOM in children was associated with extra health benefits at slightly lower direct costs and, thus, is a dominant strategy. The focus of this study was on the short-term effects of the treatment; including long-term effects in the analysis might affect the results.

Management of pain in acute otitis media in Finnish primary care.

Most treatment recommendations for acute otitis media favour active use of pain relief medication. These data comprised 3059 Finnish primary care acute otitis media patients. We found that 10.4% of the patients were prescribed or recommended analgesics, which is in contrast to treatment recommendations.

External failures as descriptor of quality in clinical microbiology laboratory services.

This study employed customer feedback surveys to assess the quality of the laboratory services provided by an accredited clinical microbiology laboratory. The purpose of the study was to classify external failures and determine the quantity of such errors, and to establish how much time was spent processing and correcting these errors, together with the costs arising. The study indicates that the quality of laboratory test results can be regarded as good based on the accuracy of the result. Customer needs were also well taken into account in practice because of the good quality of the service. However, improvements are required in providing customers with test results without delay. The cost of processing and correcting such errors was negligible. The use of a customer feedback system allows systematic monitoring of external failures. In the accredited laboratory under study, it is unnecessary to monitor continually the costs and working time involved in processing and correcting external failures. The most essential point is to monitor the effects of the quality measures taken to reduce the number of failures.

Prescription rates and diagnostic patterns are stable: a comparison of high-, medium- and low-prescribing primary care physicians treating community-acquired respiratory tract infections.

The objective was to study prescription practices of primary care physicians in prescribing antibiotics for community-acquired respiratory tract infections. Design was time series analysis and cross-sectional survey. The setting was 30 community primary health care centres. A case report form was completed for 3478 patient consultations treated by 198 office-based primary care physicians. Main outcome measures were: classification of diagnoses of respiratory tract infections made by each physician; number of antibiotic prescriptions related to these diagnoses; each physician's mean weekly number of antibiotic prescriptions during 6 months before and after the survey. Patients' risk (odds ratio: OR) to receive an antibiotic prescription from the high and medium prescribers was 5.81 (95% confidence interval [CI] 4.85-6.96) and 2.41 (95% CI 2.04-2.86), compared to low prescribers. High and medium prescribers made more diagnoses of otitis media (OR 2.07, 95% CI 1.70-2.53 and 1.85, 95% CI 1.51-2.26, respectively) and fewer diagnoses of unspecified upper respiratory tract infection (OR 0.32, 95% CI 0.26-0.38 and 0.57, 95% CI 0.48-0.68, respectively) than low prescribers. The rank of the prescription rate of high, medium and low prescriber groups remained the same for all diagnoses except pneumonia. In addition, the annual rank between high, medium and low prescriber groups remained stable; high group prescribed more antibiotics during the year than medium group, which prescribed more than low prescriber group.

Direct identification of gram-positive cocci from routine blood cultures by using AccuProbe tests.

Rapid and reliable identification of bacteria directly from blood cultures is important in clinical practice to guide appropriate antibiotic therapy. In this study, the performance of the AccuProbe (Gen-Probe, Inc., San Diego, Calif.) in direct identification of Staphylococcus aureus, Streptococcus pneumoniae, enterococci, and group A and B streptococci from positive blood culture bottles was evaluated by using 6-year routine clinical laboratory blood culture material from Paijat-Hame Central Hospital, Lahti, Finland. With the enterococcal and group A and B streptococcal probes, the diagnostic performance of the test was excellent at a cutoff value of 50,000 relative light units (RLU) as recommended by the manufacturer. However, with the S. aureus probe, although the specificity was very high (99.8%), the sensitivity was low (72.4%). To improve the clinical usability of the direct AccuProbe identification, optimal cutoff values for the individual AccuProbe tests were defined by using receiver-operating characteristic analysis. Consequently, cutoff values for S. aureus and S. pneumoniae tests were adjusted to 30,000 RLU and for enterococci and to 55,000 RLU for group A and B streptococci. With these adjustments, the performance of the AccuProbe tests, especially that for S. aureus, was significantly improved.

Disc diffusion susceptibility testing of Haemophilus influenzae by NCCLS methodology using low-strength ampicillin and co-amoxiclav discs.

OBJECTIVES: The objective of this multicentre study was to define the accuracy and reproducibility of the NCCLS disc diffusion method for Haemophilus influenzae against ampicillin and co-amoxiclav in Finnish clinical microbiology laboratories. Special attention was paid to the ability of the laboratories to detect beta-lactamase-negative ampicillin-resistant (BLNAR) strains. METHODS: Three BLNAR and two beta-lactamase-negative ampicillin-susceptible isolates (BLNAS)-originating from the American Type Culture Collection (ATCC) and UK National External Quality Assessment (UKNEQAS) schemes-were included in this study. Susceptibility tests for these isolates were performed in 26 clinical microbiology laboratories, in accordance with NCCLS guidelines. Additionally, low-strength discs for ampicillin (2 microg) and co-amoxiclav (3 microg) were tested. RESULTS: The low-strength discs for ampicillin and co-amoxiclav categorized more accurately BLNAR and BLNAS H. influenzae isolates than did the high-strength discs recommended by the NCCLS. In addition, the high-strength discs produced more major errors than the low-strength discs (22 versus six for ampicillin and 40 versus seven for co-amoxiclav). Great variation occurred in the method regardless of the antibiotic concentration of the discs. CONCLUSIONS: The use of low-content ampicillin and co-amoxiclav discs is recommended for the susceptibility testing of H. influenzae. Interpretative criteria of S > or = 17 mm and R < or = 13 mm for both discs are suggested.