Current Practices and Opportunities for Outpatient Parenteral Antimicrobial Therapy in Hospitals: A National Cross-Sectional Survey.

This nationwide study assessed how outpatient parenteral antimicrobial therapy (OPAT) is organised by Dutch acute care hospitals, the barriers experienced, and how an OPAT program affects the way hospitals organised OPAT care. We systematically developed and administered a survey to all 71 Dutch acute care hospitals between November 2021 and February 2022. Analyses were primarily descriptive and included a comparison between hospitals with and without an OPAT program. Sixty of the 71 hospitals (84.5%) responded. Fifty-five (91.7%) performed OPAT, with a median number of 20.8 (interquartile range [IQR] 10.3-29.7) patients per 100 hospital beds per year. Of these 55 hospitals, 31 (56.4%) had selection criteria for OPAT and 34 (61.8%) had a protocol for laboratory follow-up. Sixteen hospitals (29.1%) offered self-administered OPAT (S-OPAT), with a median percentage of 5.0% of patients (IQR: 2.3%-10.0%) actually performing self-administration. Twenty-five hospitals (45.5%) had an OPAT-related outcome registration. The presence of an OPAT program (22 hospitals, 40.0%) was significantly associated with aspects of well-organised OPAT care. The most commonly experienced barriers to OPAT implementation were a lack of financial, administrative, and IT support and insufficient time of healthcare staff. Concluding, hospital-initiated OPAT is widely available in the Netherlands, but various aspects of well-organised OPAT care can be improved. Implementation of a team-based OPAT program can contribute to such improvements. The observed variation provides leads for further scientific research, guidelines, and practical implementation programs.

Wide-scale study of 206 buildings in the Netherlands from 2011 to 2015 to determine the effect of drinking water management plans on the presence of Legionella spp.

Previous analysis of the Dutch National Legionella Outbreak Detection Program 2002-2012 has shown that buildings required to maintain a Legionella control plan for their drinking water installation are more likely to test positive for Legionella spp. Than buildings without such a plan (38% versus 22% of samples). To clarify this discrepancy, we analysed the results of mandatory water sample testing conducted as part of risk assessments in 206 buildings in the Netherlands from 2011 to 2015. Of the 6171 samples analysed, 16.2% exceeded the Dutch drinking water standard for Legionella spp. of 100 CFU/litre. In buildings with ≤50 tap points, the average percentage of samples containing ≥100 CFU/litre was 28.2%, and from buildings with >50 tap points, it was 12.2%. Analysis of serial samples (taken every 6 months) from each building showed that 33.2% of all buildings tested positive for at least one sample every 6 months. The overall increase was 4.4% per year. Analysis of Legionella subgroups showed that while the majority of positive samples contained L. non-pneumophila (96.9%), some samples did contain L. pneumophila serogroup 1 (1.0%) and serogroups 2-14 (2.1%). Our data suggest that the Dutch mandatory risk assessment and drinking water management plan is not sufficiently effective in preventing the proliferation of Legionella spp. and may even contribute to proliferation. This analysis should now be expanded to include other areas of the Netherlands in order to understand the geographical differences that we observed in our results, and why smaller buildings appear to be more likely to test positive for Legionella spp.

Evaluation of the Sofia Streptococcus pneumoniae FIA test for the detection of S. pneumoniae antigen in urine.

In this study, we evaluated the Sofia Streptococcus pneumoniae FIA test (Quidel Corporation, San Diego, CA, USA), a new immunofluorescence-based lateral flow test for the qualitative detection of S. pneumoniae antigen in urine or cerebrospinal fluid specimens. The analyses of 100 non-concentrated urine samples (including 50 samples from S. pneumoniae cases) showed a sensitivity and specificity (95 % CI) of, respectively, 66.0 % (52.2-77.6) and 100.0 % (92.9-100.0) for the Sofia test, and 62.0 % (48.2-74.1) and 98.0 % (89.5-99.7) for the BinaxNOW SPN Antigen Card. There were no significant differences in sensitivity and specificity between the tests (McNemar's tests, P=0.625 and P=1.000). In conclusion, this study indicates that the Streptococcus pneumoniae FIA test shows similar sensitivity and specificity rates compared to the BinaxNOW SPN Antigen Card.

Evaluation of the bioNexia Legionella Test, Including Impact of Incubation Time Extension, for Detection of Legionella pneumophila Serogroup 1 Antigen in Urine.

In this study, we compared the bioNexia test (bioMérieux, Marcy-l'Étoile, France), a new immunochromatographic assay for the detection of Legionella pneumophila serogroup 1 in urine, with the BinaxNOW urinary antigen test (Alere, Waltham, Massachusetts, USA). After 15 min of incubation (in accordance with the manufacturers' instructions), the sensitivities and specificities were, respectively, 76.5% and 97.2% for the bioNexia test and 87.1% and 100% for the BinaxNOW test. After a prolonged incubation time of 60 min, the sensitivities and specificities increased to, respectively, 89.4% and 97.2% for the bioNexia test and 91.8% and 100% for the BinaxNOW test. When the tests were read after 15 min, the concentration of discrepant urine samples increased the sensitivities to 94.1% for both tests. In conclusion, we found that although the bioNexia test showed lower sensitivity for the detection of L. pneumophila antigen in nonconcentrated urine compared to the BinaxNOW test, a prolonged incubation time as well as the use of concentrated samples showed comparable sensitivities for both tests.

Carriage of Streptococcus pneumoniae 3 years after start of vaccination program, the Netherlands.

To evaluate the effectiveness of the 7-valent pneumococcal conjugate vaccine (PCV7) program, we conducted a cross-sectional observational study on nasopharyngeal carriage of Streptococcus pneumoniae 3 years after implementation of the program in the Netherlands. We compared pneumococcal serotypes in 329 prebooster 11-month-old children, 330 fully vaccinated 24-month-old children, and 324 parents with age-matched pre-PCV7 (unvaccinated) controls (ages 12 and 24 months, n = 319 and n = 321, respectively) and 296 of their parents. PCV7 serotype prevalences before and after PCV7 implementation, respectively, were 38% and 8% among 11-month-old children, 36% and 4% among 24-month-old children, and 8% and 1% among parents. Non-PCV7 serotype prevalences were 29% and 39% among 11-month-old children, 30% and 45% among 24-month-old children, and 8% and 15% among parents, respectively; serotypes 11A and 19A were most frequently isolated. PCV7 serotypes were largely replaced by non-PCV7 serotypes. Disappearance of PCV7 serotypes in parents suggests strong transmission reduction through vaccination.

Deficient mannose-binding lectin-mediated complement activation despite mannose-binding lectin-sufficient genotypes in an outbreak of Legionella pneumophila pneumonia.

Polymorphisms leading to deficiency of mannose-binding lectin (MBL) are associated with predisposition to infection. However, MBL deficiency can be protective against intracellular pathogens that use MBL to enter host cells. The role of MBL genotype and activity in infection with the intracellular pathogen Legionella pneumophila was studied in a large outbreak of legionellosis at a Dutch flower show. A total of 141 patients, 65 exposed asymptomatic exhibition staff members and 670 unexposed blood bank donors were included for the study of MBL2 genotypes and MBL-mediated complement activation. Genotypic MBL deficiency was equally prevalent in patients and controls. Deficient MBL-mediated complement activation was more prevalent in patients. Even in patients with genotypes that confer MBL sufficiency, 20.6% lacked MBL-mediated complement activation. In most patients with MBL-sufficient genotypes who lacked MBL-mediated activation at the acute phase of disease, lectin pathway functionality was restored at convalescence. In conclusion, genotypic MBL deficiency was not a risk factor for legionellosis. However, patients with legionellosis displayed deficient MBL-mediated complement activation even with MBL-sufficient genotypes. Together, these genotypical and functional data suggest that the observed deficiency of lectin pathway activation is an effect of legionellosis rather than a risk factor for acquiring it.

Outbreak detection and secondary prevention of Legionnaires' disease: a national approach.

BACKGROUND: To stop a possible outbreak of Legionnaires' disease (LD) at an early stage an outbreak detection programme was installed in The Netherlands. METHODS: The programme consisted of sampling and controlling of potential sources to which LD patients had been exposed during their incubation period. Potential sources were considered to be true sources of infection if two or more LD patients (cluster) had visited them, or if available patients' isolates and environmental Legionella spp. were indistinguishable by amplified fragment length polymorphism genotyping. RESULTS: Rapid sampling and genotyping as well as cluster recognition helped to target control measures. Despite these measures, two small outbreaks were only stopped after renewal of the water system. The combination of genotyping and cluster recognition lead to 29 of 190 (15%) patient-source associations. CONCLUSION: Systematic sampling and cluster recognition can contribute to outbreak detection and lead to cost-effective secondary prevention of Legionnaires' disease.

Sensitivity of three serum antibody tests in a large outbreak of Legionnaires' disease in the Netherlands.

In 1999, an outbreak involving 188 patients with Legionnaires' disease (LD) occurred at a flower show in the Netherlands. This large outbreak provided the opportunity to evaluate serum antibody tests to assay anti-Legionella pneumophila, since limited data are available on the sensitivity of these tests. The sensitivities of an indirect serotype 1-6 immunofluorescence antibody test (IFAT), a rapid micro-agglutination test (RMAT) IgM serotype 1 antibody assay, and an ELISA to detect IgM and IgG serotype 1-7 antibodies, were evaluated using serum samples from LD patients related to the 1999 outbreak. Sensitivity was calculated using positive culture and/or a positive urinary antigen test as the gold standard in outbreak-related patients with radiographically confirmed pneumonia who fulfilled the epidemiological criteria. The IFAT, RMAT and ELISA showed sensitivities of 61, 44 and 64%, respectively. The sensitivity of the three tests combined was 67%. In epidemic situations, however, high standing titres may be included in the laboratory evidence of LD cases. In the study population, high standing titres were found in 16% of cases. If the presence of high standing antibody titres was added to the criteria of a positive test, the sensitivities of IFAT, RMAT and ELISA were 86, 48 and 75%, respectively. The sensitivity was 91% for all tests combined. The higher sensitivity for the combined use of tests is offset by a reduction in specificity to 97.6%. The results of this study indicate that using a combination of serologic tests in pneumonia patients suspected to have LD does not substantially improve sensitivity. The results suggest that in the microbiological diagnosis of LD, both IFAT and ELISA are reasonably sensitive assays. In an epidemic situation, both tests are highly sensitive, the IFAT more so than the ELISA.

A case of Legionnaires' disease caused by aspiration of ice water.

The authors discuss the case of a 79-year-old patient who suffered from a swallowing disorder and developed Legionnaires' disease 2 days after her dismissal from an orthopedics ward, where she had recovered from hip surgery. To determine the source of the Legionnaires' disease, the authors performed an environmental investigation, which included a national, standardized questionnaire and a microbiological investigation of suspected sources. The investigation revealed ice from an ice-making machine in the hospital as the most probable source of the infection through aspiration, even though the hospital had rigorously adhered to strict assessment and decontamination schedules. The infectious serogroup was one that was not common to the area. From the data available, the authors inferred that a dose of 1-2000 colony-forming units might have caused Legionnaires' disease in this patient.

Domestic exposure to legionellae for Dutch Legionnaires' disease patients.

The source of infection for travelers who develop Legionnaires' disease (LD) shortly after a journey abroad is difficult to ascertain. Infection is likely to have occurred abroad, but could also have occurred at the patient's own residence. The authors conducted a case-control study to determine risk for acquiring LD at home in the Netherlands after traveling abroad. They compared homes of 44 traveling LD patients with 44 homes of nontraveling LD patients, using logistic regression models. Geographic distribution was confounding the association between traveling and presence of Legionella spp. in residences; adjustment was necessary. In traveler's homes, legionellae were present more often, with crude and adjusted OR (95% CI) being 1.6 (0.5-5.0) and 1.4 (0.4-4.4), respectively. The authors' findings indicate that the patient's residence can be a potential source of infection after traveling.

Legionnaires' disease at a Dutch flower show: prognostic factors and impact of therapy.

After a large outbreak of Legionnaires' disease in the Netherlands, we determined risk factors for intensive care unit (ICU) admission and death and the impact of adequate therapy on ICU-free survival among 141 hospitalized patients. Overall mortality rate was 13%, and ICU mortality rate was 36%. Smoking, temperature >38.5 degrees C, and bilateral infiltrates shown on chest x-ray were independent risk factors for ICU admission or death (all p<0.05). Starting adequate therapy within 24 hours after admission resulted in a higher ICU-free survival rate compared to therapy initiation after 24 hours: 78% versus 54%, respectively (p=0.005). However, delay in providing therapy to patients with urinary antigen tests with negative results did not influence outcome. These data suggest that by using the urinary antigen test on admission a more tailored approach to patients with community-acquired pneumonia may be applied.

Sensitivity of three urinary antigen tests associated with clinical severity in a large outbreak of Legionnaires' disease in The Netherlands.

In 1999 an outbreak involving 188 patients with Legionnaires' disease (LD) occurred among visitors to a flower show in the Netherlands. Two enzyme immunoassays (Binax and Biotest) and one immunochromatographic assay (Binax NOW) were tested, using urine samples from LD patients from the 1999 outbreak. Sensitivity was calculated using positive culture and/or seroconversion as the "gold standard" in outbreak-related patients with radiographically confirmed pneumonia who fulfilled the epidemiological critera. The Binax EIA, Biotest EIA, and Binax NOW assay showed overall sensitivities of 69, 71, and 72%, respectively. When the tests were performed with concentrated urine samples, the overall sensitivities increased to 79, 74, and 81%, respectively. Using multiple logistic regression analysis with backward elimination, a statistically significant association was found between clinical severity and test sensitivity for all tests. For patients with mild LD, the test sensitivities ranged from 40 to 53%, whereas for patients with severe LD who needed immediate special medical care, the sensitivities reached 88 to 100%. These findings have major implications for the diagnostic process in patients with mild pneumonia and suggest that patients with mild pneumonia may go underdiagnosed if urine antigen tests alone are used.

A large outbreak of Legionnaires' disease at a flower show, the Netherlands, 1999.

In 1999, an outbreak of Legionnaires' disease affected many visitors to a flower show in the Netherlands. To identify the source of the outbreak, we performed an environmental investigation, as well as a case-control study among visitors and a serologic cohort study among exhibitors to measure exposure to possible sources. Of 77,061 visitors, 188 became ill (133 confirmed and 55 probable cases), for an attack rate of 0.23% for visitors and 0.61% for exhibitors. Two whirlpool spas in halls 3 and 4 of the exhibition and a sprinkler in hall 8 were culture positive for Legionella pneumophila. One of three genotypes found in both whirlpool spas was identical to the isolates from 28 of 29 culture-positive patients. Persons who paused at the whirlpool spa in hall 3 were at increased risk for becoming ill. This study illustrates that whirlpool spas may be an important health hazard if disinfection fails.