Hospital-acquired Legionella pneumonia outbreak at an academic medical center: Lessons learned

BackgroundAn outbreak of Legionella pneumonia occurred at a university hospital using copper-silver ionization for potable water disinfection. We present the epidemiological and laboratory investigation of the outbreak, and associated case-control study.MethodsCases were defined by syndrome compatible with Legionella pneumonia with laboratory-confirmed Legionella infection. The water circuit and disinfection system were assessed, and water samples collected for Legionella culture. Whole genome multi-locus sequence typing (wgMLST) was used to compare the genetic similarity of patient and environmental isolates. A case-control study was conducted to identify risk factors for Legionella pneumonia.ResultsWe identified 13 cases of hospital-acquired Legionella. wgMLST revealed >99.9% shared allele content among strains isolated from clinical and water samples. Smoking (P= .008), steroid use (P= .007), and documented shower during hospitalization (P= .03) were risk factors for Legionella pneumonia on multivariable analysis. Environmental assessment identified modifications to the hospital water system had occurred in the month preceding the outbreak. Multiple mitigation efforts and application of point of use water filters stopped the outbreak.ConclusionsPotable water system Legionella colonization occurs despite existing copper-silver ionization systems, particularly after structural disruptions. Multidisciplinary collaboration and direct monitoring for Legionella are important for outbreak prevention. Showering is a modifiable risk factor for nosocomial Legionella pneumonia. Shower restriction and point-of-use filters merit consideration during an outbreak.     

Environmental surveillance of Legionella in tourist facilities of the Balearic Islands,Spain, 2006 to 2010 and 2015 to 2018

BackgroundLegionnaires’ disease is a respiratory illness often associated with hotels and travel. Spain is a major tourist destination and one of the European countries with most cases of Legionnaires’ disease , both community- and travel-associated. However, the prevalence of Legionella in tourist facilities is unknown.AimThe present investigation aimed to survey the tourist facilities in the Balearic Islands, Spain, for Legionella prevalence.MethodsWe visited tourist facilities in the Balearic Islands in two different periods (2006–2010 and 2015–2018) and took water samples following national and international guidelines. Legionella was investigated by culture methods following international standards (ISO 11731:1998).ResultsWe evaluated 13,472 samples from 465 facilities. Bacteria of the Legionella genus were detected in 65.4% of the surveyed facilities. Contamination of the facilities was significantly higher during the second decade (54.5 vs 78.6%). The most frequent colonisers were L. pneumophila serogroup 2–14. We detected the pathogen in 15.9% and 6.9% of hot and cold water distribution systems samples, respectively. The Legionella contamination rate in cold water systems samples was higher when free chlorine levels were < 0.2 mg/L and at > 25 °C temperatures, while in the hot water systems samples, the contamination rate was higher at < 50 °C. Of the samples from hot tubs, 10.9% were contaminated.Conclusion Legionella prevalence in hotels in the Balearic Islands was high but the contamination rates depended on the installations. Corrective measures are still needed to improve Legionella control.     

Point-of-use filters for prevention of health care–acquired Legionnaires’ disease: Field evaluation of a new filter product and literature review

BackgroundThe Centers for Medicare & Medicaid Services requires that health care facilities assess their building water systems and minimize the risk of growth and spread of Legionella and other waterborne pathogens. Increasingly, point-of-use (POU) filters are being used to prevent exposure to these pathogens. This study provides efficacy and performance specifications (membrane size, pore size, and use restrictions), which will aid in selecting POU filters.MethodsNew faucet and shower filters rated for 62 days of use were evaluated at an acute care facility in Southwestern Ontario, Canada. Five faucets and 5 showers served as controls or were equipped with filters. Hot water samples were collected weekly for 12 weeks and cultured for Legionella, heterotrophic plate count, and Pseudomonas. Literature searches for articles on POU filters used in health care settings were performed using PubMed and Google Scholar. Filter specifications from 5 manufacturers were also compared.ResultsThe 62-day POU filters installed on both faucets and showers eliminated Legionella and reduced heterotrophic plate count concentrations for 12 weeks. No Pseudomonas was recovered during this study. Twenty peer-reviewed studies are summarized, and 21 features of 53 POU filters have been compiled.ConclusionsThe information provides infection preventionists and facility engineers with information to verify claims from manufacturers and compare differences among POU products, including validated efficacy, filter design, and operational specifications.     

Legionella endocarditis: A case report and review

BackgroundLegionella is a well known but infrequent cause of bacterial endocarditis.MethodsWe report a case of endocarditis caused by Legionella spp. We reviewed previously reported cases in PubMed, Google Scholar and in references included in previous reports, and summarized relevant clinical data.ResultsA 63-year-old man with a history of aortic valve replacement developed persistent fever and monoarthritis. Transesophageal echocardiography showed perivalvular abscess. He died during surgery. Blood and valve cultures were negative. Legionella spp. was demonstrated with 16S-rRNA PCR from the resected material. Twenty cases of Legionella endocarditis have been reported. Harboring a prosthetic valve was the main risk factor. Prognosis was favorable, both for patients treated with or without surgical valve replacement. Overall mortality was <10%.ConclusionsLegionella is an infrequent cause of endocarditis. It frequently requires surgical treatment. Prognosis is good. Molecular techniques are likely to become the gold standard for diagnosis.     

Actualités sur les infections à Legionella

Legionella-related disease is caused by an intracellular bacteria mainly living in water. Contamination results from inhalation of Legionella sp containing aerosolized water. Main risk factors are tobacco, immunodeficiency, and advanced age. Antigenuria is the cornerstone of the diagnosis. Immunocompromised patients, more commonly infected with non pneumophila Legionella, present negative antigenuria, and culture and PCR are essential for the diagnosis. Legionnaires’ disease may be severe, especially in elderly and/or immunocompromised patients. Mortality rate varies from 10 % in the general population to 50 % in intensive care. Treatment is based on macrolides or fluoroquinolones. Antibiotic resistance is very rare.     

Legionellosis in Transplantation

Legionella species are emerging opportunistic pathogens in hematopoietic stem cell and solid organ transplant recipients, associated with significant morbidity and mortality. The clinical and radiological features of Legionella infections can mimic other opportunistic pathogens in these profoundly immunocompromised patients. Diagnosis in transplant patients is challenging as non-pneumophila Legionella infections, for which these patients are at risk, cannot be identified using the urinary antigen test. Changes in management of transplant recipients and changes in Legionella epidemiology suggest that the number of transplant patients potentially exposed to Legionella spp. may be on the rise. Yet, evidence-based, transplant-specific guidelines for managing and preventing Legionella infections are not currently available. In this article, we review the epidemiology, clinical features, diagnostic challenges, treatment options, and preventive strategies of Legionella infections in these high-risk patient populations.     

Reusable terminal tap water filters for nosocomial legionellosis prevention

Hospital water supplies often contain Legionella spp. and therefore represent a source of nosocomial infection especially for immunocompromised patients in intensive care or organ transplant units. Therefore, pathogen-free water should be provided for the care of these patients. Approaches of long-term Legionella spp. eradication from the plumbing system are rarely successful. Exposition prophylaxis might be another reasonable approach in high-risk patient care. To investigate the ability to provide water free of Legionella spp. with reusable water filters, a surveillance of splash water samples was performed. After determining the burden of Legionella spp. in the plumbing system of a paediatric oncological ward by ten unfiltered splash water samples, ten designated water taps were provided with terminal tap water filters that could be reprocessed by thermal disinfection. A further 129 samples were taken after a usage interval of 7 days and 10 more samples after a usage interval of 21 days before reprocessing the filters. All samples were checked for growth of Legionella spp. as well as other pathogenic bacteria. A total germ count of all samples was also performed. Half of the unfiltered splash water samples revealed growth of Legionella spp. All filtered water samples remained free of Legionella. Total germ count did not increase before a usage interval of 7 days. We believe the water filters tested are suitable for prevention of nosocomial legionellosis when reprocessed after 7 days as recommended by the manufacturer. To avoid retrograde contamination of filters, education of staff and patients in handling these devices is mandatory.     

Suspected Legionella-Induced Perimyocarditis in an Adult in the Absence of Pneumonia: A Rare Clinical Entity

Legionella infection can manifest itself in many clinical forms, most commonly as pneumonia, but rarely in the form of myocardial involvement. Legionella with myocardial involvement independent of pneumonia is almost never seen in the adult population and therefore is cited only a handful of times in the medical literature. When reported, Legionella carditis itself typically occurs as an isolated pericarditis with effusion. Cases of isolated Legionella with myocardial involvement, but without associated pneumonia, have been reported among children. To our knowledge, there are no reported cases of Legionella myocarditis and pericarditis presenting concurrently with or without pneumonia, in either an adult or a pediatric population.Herein, we report a rare manifestation of Legionella pneumophila-induced perimyocarditis (strongly suspected, if not incontrovertibly proved) in an adult, in the absence of pneumonia.Key words: Antibodies, bacterial; bacterial infections/diagnosis; Legionella; Legionella pneumophila; Legionnaires'' disease; middle aged; myocarditis; pericarditisLegionella infection can manifest itself in many different clinical presentations—most commonly as pneumonia, but rarely as myocardial involvement. The severity of illness at presentation varies from mild, nonspecific findings to profound respiratory or multiorgan failure. Extrapulmonary legionellosis is rare; but when extrapulmonary manifestation does occur, its most common site of infection is the heart, especially in the pediatric population.¹ Legionella carditis is rarely seen independent of pneumonia in the adult population and is more commonly observed in pediatric patients.² Herein, we report a case of suspected perimyocarditis, a rare manifestation of Legionella pneumophila in an adult, in the absence of pneumonia.     

Sequence-based typing of clinical and environmental Legionella pneumophila isolates in Shenyang,China

IntroductionWe performed SBT (sequence-based typing) on clinical and environmental Legionella pneumophila isolates in Shenyang (China). We analyzed and compared the results with those obtained by PFGE (pulsed field gel electrophoresis).MethodsTwenty-two L. pneumophila isolates were collected from two patients with L. pneumophila infection, two hospitals, and 13 office buildings. There were two clinical isolates, one strain isolated from domestic tap water, another from shower water and 18 strains from cooling tower water. All these isolates were analyzed by SBT and PFGE methods.ResultsThe 22 isolates were divided into 7 types by SBT. Five isolates belonged to novel sequence types (ST2345, ST2344, ST2406, ST2407, and ST2408) and one isolate belonged to ST328. The STs were not obtained for two of the isolates. The remaining 14 isolates belonged to ST1. PFGE typing divided the 22 isolates into 14 pulsotypes. The main pulsotype was SYC, which included seven isolates.ConclusionBoth typing methods showed that predominant clonal lines exist in the Shenyang region, with high levels of genetic polymorphisms. Five novel STs were identified, indicating a unique genetic composition of L. pneumophila strains in this region, which are significantly different from those found in other environmental water systems in the world.     

A community-acquired Legionnaires’ disease outbreak caused by Legionella pneumophila serogroup 2: an uncommon event,Italy, August to October 2018

In September 2018 in Brescia province, northern Italy, an outbreak of Legionnaires'' disease (LD) caused by Legionella pneumophila serogroup 2 (Lp2) occurred. The 33 cases (two fatal) resided in seven municipalities along the Chiese river. All cases were negative by urinary antigen test (UAT) and most were diagnosed by real-time PCR and serology. In only three cases, respiratory sample cultures were positive, and Lp2 was identified and typed as sequence type (ST)1455. In another three cases, nested sequence-based typing was directly applied to respiratory samples, which provided allelic profiles highly similar to ST1455. An environmental investigation was undertaken immediately and water samples were collected from private homes, municipal water systems, cooling towers and the river. Overall, 533 environmental water samples were analysed and 34 were positive for Lp. Of these, only three samples, all collected from the Chiese river, were Lp2 ST1455. If and how the river water could have been aerosolised causing the LD cases remains unexplained. This outbreak, the first to our knowledge caused by Lp2, highlights the limits of UAT for LD diagnosis, underlining the importance of adopting multiple tests to ensure that serogroups other than serogroup 1, as well as other Legionella species, are identified.     

Caspase-11 stimulates rapid flagellin-independent pyroptosis in response to Legionella pneumophila

A flagellin-independent caspase-1 activation pathway that does not require NAIP5 or NRLC4 is induced by the intracellular pathogen Legionella pneumophila. Here we demonstrate that this pathway requires caspase-11. Treatment of macrophages with LPS up-regulated the host components required for this caspase-11 activation pathway. Activation by Legionella differed from caspase-11 activation using previously described agonists in that Legionella caspase-11 activation was rapid and required bacteria with a functional type IV secretion system called Dot/Icm. Legionella activation of caspase-11 induced pyroptosis by a mechanism independent of the NAIP/NLRC4 and caspase-1 axis. Legionella activation of caspase-11 stimulated activation of caspase-1 through NLRP3 and ASC. Induction of caspase-11–dependent responses occurred in macrophages deficient in the adapter proteins TRIF or MyD88 but not in macrophages deficient in both signaling factors. Although caspase-11 was produced in macrophages deficient in the type-I IFN receptor, there was a severe defect in caspase-11–dependent pyroptosis in these cells. These data indicate that macrophages respond to microbial signatures to produce proteins that mediate a capsase-11 response and that the caspase-11 system provides an alternative pathway for rapid detection of an intracellular pathogen capable of evading the canonical caspase-1 activation system that responds to bacterial flagellin.     

Isolation and identification of Acanthamoeba from Taiwan spring recreation areas using culture enrichment combined with PCR

In the study, 52 spring water samples were collected from three hot spring recreation areas in northern Taiwan and Acanthamoebae were isolated from 11 samples (21.2%) on two hot spring recreation areas and mainly present in the hot spring water, hot tubs and wastewater. The most frequently identified Acanthamoeba genotype was T15, followed by T6, and then T5. Genotype T1, T2, T3 and T4 were detected once, respectively. The presence or absence of Acanthamoeba within the spring water samples showed significant difference with the levels of heterotrophic plate counts (HPC). Genotype T2-T6 and genotype T15, the organism responsible for Acanthamoeba keratitis, and the Acanthamoeba species organism, retained pathogenic Legionella, and should be considered a potential health threat associated with human activities in spring recreation areas.     

TandemHeart as a Bridge to Recovery in Legionella Myocarditis

Legionnaires'' disease is the designation for pneumonia caused by the Legionella species. Among the rare extrapulmonary manifestations, cardiac involvement is most prevalent, in the forms of myocarditis, pericarditis, postcardiotomy syndrome, and prosthetic valve endocarditis. Mechanical circulatory support has proved to be a safe and effective bridge to myocardial recovery in patients with acute fulminant myocarditis; however, to our knowledge, this support has not been used in infectious myocarditis specifically related to Legionellosis.We describe a case of Legionella myocarditis associated with acute left ventricular dysfunction and repolarization abnormalities in a 48-year-old man. The patient fully recovered after left ventricular unloading with use of a TandemHeart percutaneous ventricular assist device. In addition, we review the English-language medical literature on Legionella myocarditis and focus on cardiac outcomes.     

Significance of Hypophosphatemia in Patients with Pneumonia

Objective Phosphate is a fundamental element involved in a number of physiological pathways. A previous study showed abnormal laboratory findings and a higher mortality in hypophosphatemic patients than in normophosphatemic patients with pneumonia. Sporadic cases of pneumonia due to Legionella spp., Streptococcus pneumoniae, and viruses have been reported; however, the significance of hypophosphatemia in patients with pneumonia has not been adequately studied. We determined whether or not hypophosphatemia in patients with community-acquired pneumonia (CAP) was associated with specific pathogens, patient factors, disease severity, and mortality. Method We retrospectively analyzed 600 patients with CAP who were admitted to our hospital between January 1, 2010, and December 31, 2019. Results Hypophosphatemia was found in 72 (12.0%) of the 600 patients. The most frequent causative microbial agents of CAP in patients with hypophosphatemia were S. pneumoniae, Legionella spp., and influenza virus, whereas in severely ill patients with hypophosphatemia, influenza virus was the most common. Legionella spp., diabetes mellitus, and severe pneumonia were the independent factors for hypophosphatemia in the multivariable analysis. An impaired performance status, severe status on admission, interstitial pneumonia, bacteremia, and guideline-discordant therapy were the independent factors associated with mortality in the multivariable analysis. Hypophosphatemia was not significantly associated with mortality but showed a trend towards higher mortality in the multivariable analysis. Conclusion Hypophosphatemia was not associated with the prognosis in patients with CAP. However, the significance of hypophosphatemia for clinicians lies in the laboratory findings that predict abnormal glucose metabolism, Legionella infection, and severe disease.     

An outbreak investigation of Legionella non-pneumophila Legionnaires’ disease in Sweden,April to August 2018: Gardening and use of commercial bagged soil associated with infections

In early June 2018, an increase in non-travel-related cases of Legionella non-pneumophila Legionnaires’ disease (LD) was observed in Sweden and a national outbreak investigation was started. Outbreak cases were defined as notified confirmed or probable cases of L. non-pneumophila LD, with symptom onset after 1 April 2018. From April to August 2018, 41 cases were reported, 30 of whom were identified as L. longbeachae. We conducted a case–control study with 27 cases and 182 matched controls. Results from the case–control study indicated that gardening and handling commercial bagged soil, especially dusty dry soil, were associated with disease. L. longbeachae was isolated in soils from cases’ homes or gardens, but joint analysis of soil and human specimens did not identify any genetic clonality. Substantial polyclonality was noted between and within soil samples, which made finding a genetic match between soil and human specimens unlikely. Therefore, whole genome sequencing may be of limited use to confirm a specific soil as a vehicle of transmission for L. longbeachae. Handling soil for residential gardening was associated with disease and the isolation of L. longbeachae in different soils provided further evidence for Legionella non-pneumophila infection from soil.     

Clinical and computed tomographic features of Legionella pneumonia with negative urine antigen test results

BackgroundLegionella spp. can cause severe pneumonia and most Legionella pneumonia (LP) cases are diagnosed using the urine antigen test (UAT). However, diagnosis of LP with negative UAT results (LPNUAT) is challenging. We investigated the clinical and radiological features of LPNUAT.MethodsWe retrospectively collected LP cases with positive UAT (LPPUAT) and cases of suspected LP with negative UAT that were examined by Legionella culture between July 2014 and March 2020. We investigated the clinical and CT findings for LP that showed negative UAT results and was diagnosed by culture and compared these findings with those for other pneumonias suspicious for LP with negative results in UAT and Legionella culture (OPSLP).ResultsEight LPNUAT, 20 LPPUAT, and 19 OPSLP cases were included in this study. There were no significant differences in the clinical and CT findings between LPPUAT and LPNUAT when examined by UAT. In LPNUAT, dyspnea, renal dysfunction, liver dysfunction, and bilateral lesions were more commonly observed and inflammatory changes and the number of affected lobes were significantly higher when examined by culture than when examined by UAT. Comparison to OPSLP, LPNUAT did not show such differences, but rather showed disturbances in consciousness, hyponatremia and rhabdomyolysis. Furthermore, lobar consolidation was observed more frequently and bronchial wall thickening and centrilobular nodules were observed less frequently in LPNUAT.ConclusionsLP characteristics such as disturbance of consciousness, hyponatremia, rhabdomyolysis, lobar consolidation, and less bronchial wall thickening and centrilobular nodule contribute to the diagnosis of LP in patients with negative UAT results.     

Structural mechanism of host Rab1 activation by the bifunctional Legionella type IV effector SidM/DrrA

Bacterial pathogens deliver effector proteins with diverse biochemical activities into host cells, thereby modulating various host functions. Legionella pneumophila hijacks host vesicle trafficking to avoid phagosome–lysosome fusion, a mechanism that is dependent on the Legionella Dot/Icm type IV secretion system. SidM/DrrA, a Legionella type IV effector, is important for the interactions of Legionella-containing vacuoles with host endoplasmic reticulum–derived vesicles. SidM is the only known protein that catalyzes both the exchange of GDP for GTP and GDI displacement from small GTPase Rab1. We determined the crystal structures of SidM alone (residues 317–647) and SidM (residues 193–550) in complex with nucleotide-free WT Rab1. The SidM structure contains an N-terminal helical domain with a potential new function, a Rab1-activation domain, and a C-terminal phosphatidylinositol 4-phosphate–binding P4M domain. The Rab1-activation domain has extensive strong interactions mainly with Rab1 switch I and II regions that undergo substantial conformational changes on SidM binding. Mutations of switch-contacting residues in SidM attenuate both the nucleotide exchange and GDI displacement activities. Structural comparisons of Rab1 in the SidM complex with Rab1-GDP and Ypt1-GDP in the GDI complex identify key conformational changes that disrupt the nucleotide and GDI binding of Rab1. Further biochemical and structural analyses reveal a unique mechanism of coupled GDP release and GDI displacement likely triggered by the SidM-induced drastic displacement of switch I of Rab1.     

Spontaneous rupture of the spleen associated with Legionella pneumonia

Spontaneous rupture of the spleen associated with Legionella pneumonia is a rare and life-threatening complication; only three cases have been reported to date. The authors describe a case of a 47-year-old man who presented with pneumonia and abdominal pain. He underwent a splenectomy, and was successfully treated with clarithromycin and levofloxacin.     

Migration of Volatile Organic Compounds (VOCs) from PEX-a Pipes into the Drinking Water during the First Five Years of Use

A brand-new office building in Rauma, Finland, was used to study the first five years of PEX-a drinking water pipes in normal use. Both pipe material and water samples from hot and cold-water pipelines were analyzed. Migration of volatile organic compounds (VOC) from the PEX-a pipes into the drinking water was observed to decrease rapidly during the first months. Deterioration of the PEX-a material was observed to take place due to the wearing down of organic antioxidants added into the PEX-a material during the manufacturing of the pipes. Tert-butyl alcohol (TBA) concentrations were high during the first months after commissioning of use. The stagnation time of the drinking water in contact with the PEX-a material before the actual water sample was taken had a major impact on analyzed migration of organic compounds. Hence, the amount of organic compounds able to migrate from materials into the drinking water will increase when the stagnation time increases. In this study, the water samples were taken after overnight stagnation, whereas in normal use it is advisable to run water properly before drinking it. Instructions will be needed for the average user to avoid harmful health effects.