Community-acquired Cases Research Articles

Community-acquired Respiratory Virus Cases Mimic COVID-19 on Lung Computed Tomography.

We herein report four patients with community-acquired respiratory virus (CRV) infection. Although they had no history of contact with any individual with coronavirus disease 2019 (COVID-19), they were suspected of having COVID-19 based on findings of high-resolution computed tomography (CT) of the lungs. Among the four patients, two were infected with rhinovirus, one with metapneumovirus, and one with influenza A. Their chest CT findings were similar to those of COVID-19 patients reported in previous studies. Both CRV infection and COVID-19 can show various patterns on chest CT. CRV infection is thus indistinguishable from COVID-19 based on CT findings alone.

A Systematic Review and Meta-Analysis of Inpatient Mortality Associated With Nosocomial and Community COVID-19 Exposes the Vulnerability of Immunosuppressed Adults.

BackgroundLittle is known about the mortality of hospital-acquired (nosocomial) COVID-19 infection globally. We investigated the risk of mortality and critical care admission in hospitalised adults with nosocomial COVID-19, relative to adults requiring hospitalisation due to community-acquired infection.MethodsWe systematically reviewed the peer-reviewed and pre-print literature from 1/1/2020 to 9/2/2021 without language restriction for studies reporting outcomes of nosocomial and community-acquired COVID-19. We performed a random effects meta-analysis (MA) to estimate the 1) relative risk of death and 2) critical care admission, stratifying studies by patient cohort characteristics and nosocomial case definition.Results21 studies were included in the primary MA, describing 8,251 admissions across 8 countries during the first wave, comprising 1513 probable or definite nosocomial COVID-19, and 6738 community-acquired cases. Across all studies, the risk of mortality was 1.3 times greater in patients with nosocomial infection, compared to community-acquired (95% CI: 1.005 to 1.683). Rates of critical care admission were similar between groups (Relative Risk, RR=0.74, 95% CI: 0.50 to 1.08). Immunosuppressed patients diagnosed with nosocomial COVID-19 were twice as likely to die in hospital as those admitted with community-acquired infection (RR=2.14, 95% CI: 1.76 to 2.61).ConclusionsAdults who acquire SARS-CoV-2 whilst already hospitalised are at greater risk of mortality compared to patients admitted following community-acquired infection; this finding is largely driven by a substantially increased risk of death in individuals with malignancy or who had undergone transplantation. These findings inform public health and infection control policy and argue for individualised clinical interventions to combat the threat of nosocomial COVID-19, particularly for immunosuppressed groups.Systematic Review RegistrationPROSPERO CRD42021249023

Diversity of Rotavirus Strains in Children; Results From a Community-Based Study in Nepal.

Objective: The objectives of this study were to describe the incidence and genetic diversity of Rotavirus (RV) infection among children up to 3 years of age in a community in Nepal.Methods: We investigated community-acquired cases of asymptomatic and symptomatic RV infections in children from birth to 36 months of age in a community-based birth cohort in Bhaktapur, Nepal. Monthly surveillance and diarrheal stool samples were collected from 240 children enrolled at birth, of which 238 completed the 3 years of follow-up. Samples were screened for rotavirus by Enzyme Immuno Assay (EIA). All RV screened positives were further genotyped by reverse transcription-polymerase chain reaction for the capsid genes VP7 and VP4.Results: In total, 5,224 stool samples were collected from 238 children, followed from birth to 36 months of age. Diarrhea occurred in 92.4% (230/238) of all children in the cohort. During the 3 years study period, RV was more frequently seen in children with symptoms (7.6%) than in non-symptomatic children (0.8%). The highest RV detection rate was found in younger children between 3 and 21 months of age. Although rotavirus is known as winter diarrhea, it was detected throughout the year except in August. The highest positivity rate was observed in the months between December and March, with a peak in January. Four common G types were seen: G2 (30%), G1 (29%), G12 (19%), and G9 (16%). The most predominant genotypes seen were G2P[4] (30%), followed by G1P[8] (27.0%), G12P[6] (14.0%), G9P[8] (10%), and remaining were mixed, partial, and untyped.Conclusion: Our study confirms that rotavirus is a common cause of gastroenteritis in young children in the community. The prevalence and pathogenicity of rotavirus infection differed by age. There was substantial variability in circulating strains in the community samples compared to samples collected from hospitals. This shows the importance of including community-based surveillance systems to monitor the diversity of circulating rotavirus strains in Nepal.

917Stakeholder analysis to develop a national outbreak response plan for Q fever in Australia

917Stakeholder analysis to develop a national outbreak response plan for Q fever in Australia

Healthcare-associated COVID-19 in England: A national data linkage study

ObjectivesNosocomial transmission was an important aspect of SARS-CoV-1 and MERS-CoV outbreaks. Healthcare-associated SARS-CoV-2 infection has been reported in single and multi-site hospital-based studies in England, but not nationally.MethodsAdmission records for all hospitals in England were linked to SARS-CoV-2 national test data for the period 01/03/2020 to 31/08/2020. Case definitions were: community-onset community-acquired, first positive test <14 days pre-admission, up to day 2 of admission; hospital-onset indeterminate healthcare-associated, first positive on day 3–7; hospital-onset probable healthcare-associated, first positive on day 8–14; hospital-onset definite healthcare-associated, first positive from day 15 of admission until discharge; community-onset possible healthcare-associated, first positive test ≤14 days post-discharge.ResultsOne-third (34.4%, 100,859/293,204) of all laboratory-confirmed COVID-19 cases were linked to a hospital record. Hospital-onset probable and definite cases represented 5.3% (15,564/293,204) of all laboratory-confirmed cases and 15.4% (15,564/100,859) of laboratory-confirmed cases among hospital patients. Community-onset community-acquired and community-onset possible healthcare-associated cases represented 86.5% (253,582/293,204) and 5.1% (14,913/293,204) of all laboratory-confirmed cases, respectively.ConclusionsUp to 1 in 6 SARS-CoV-2 infections among hospitalised patients with COVID-19 in England during the first 6 months of the pandemic could be attributed to nosocomial transmission, but these represent less than 1% of the estimated 3 million COVID-19 cases in this period.

The Experience of Implementing a National Antimicrobial Resistance Surveillance System in Brazil

Antimicrobial resistance (AMR) is a major public health threat of global proportions, which has the potential to lead to approximately ten million deaths per year by 2050. Pressured by this wicked problem, in 2014, the World Health Organization launched a call for member states to share AMR data through the implementation of the Global Antimicrobial Resistance Surveillance System (GLASS), to appropriately scale and monitor the general situation world-widely. In 2017, Brazil joined GLASS and, in 2018, started its own national antimicrobial surveillance program (BR-GLASS) to understand the impact of resistance in the country. We compiled data obtained from the complete routine of three hospitals' microbiology labs during the year of 2018. This pilot data sums up to 200,874 antimicrobial susceptibility test results from 11,347 isolates. It represents 119 different microorganisms recovered from 44 distinct types of clinical samples. Specimens came from patients originating from 301 Brazilian cities, with 4,950 of these isolates from presumed Healthcare-Associated Infections (HAIs) and the other 6,397 community-acquired cases. The female population offered 58% of the collected samples, while the other 42% were of male origin. The urinary tract was the most common topography (6,372/11,347 isolates), followed by blood samples (2,072/11,347). Gram-negative predominated the bacterial isolates: Escherichia coli was the most prevalent in general, representing 4,030 isolates (89.0% of these from the urinary tract). Coagulase-negative Staphylococci were the most prevalent bacteria in blood samples. Besides these two species, the ESKAPE group have consolidated their prevalence. Regarding drug susceptibility results, 141,648 (70.5%) were susceptible, 9,950 (4.9%) intermediate, and 49,276 (24.5%) resistant. Acinetobacter baumannii was the most worrisome microorganism, with 65.3% of the overall antimicrobial susceptibility tests showing resistance, followed by ESBL-producing Klebsiella pneumoniae, with a global resistance rate of 59%. Although this is a pilot project (still limited to one state), this database shows the importance of a nation-wide surveillance program,[153mm][-12mm] Q14 especially considering it already had patients coming from 301 distinct counties and 18 different states. The BR-GLASS Program is an ongoing project that intends to encompass at least 95 hospitals distributed in all five geographical regions in Brazil within the next 5 years.

The search for novel treatment strategies for Streptococcus pneumoniae infections.

ABSTRACTThis review provides an overview of the most important novel treatment strategies against Streptococcus pneumoniae infections published over the past 10 years. The pneumococcus causes the majority of community-acquired bacterial pneumonia cases, and it is one of the prime pathogens in bacterial meningitis. Over the last 10 years, extensive research has been conducted to prevent severe pneumococcal infections, with a major focus on (i) boosting the host immune system and (ii) discovering novel antibacterials. Boosting the immune system can be done in two ways, either by actively modulating host immunity, mostly through administration of selective antibodies, or by interfering with pneumococcal virulence factors, thereby supporting the host immune system to effectively overcome an infection. While several of such experimental therapies are promising, few have evolved to clinical trials. The discovery of novel antibacterials is hampered by the high research and development costs versus the relatively low revenues for the pharmaceutical industry. Nevertheless, novel enzymatic assays and target-based drug design, allow the identification of targets and the development of novel molecules to effectively treat this life-threatening pathogen.

Economic burden and cost-effectiveness of therapies for Clostridiodes difficile infection: a narrative review.

Clostridioides difficile is the most common cause of healthcare-associated diarrhea. Disease complications as well as recurrent infections contribute significantly to morbidity and mortality. Over the past decades, there has been a rapid increase in the incidence of C. difficile infection (CDI), with a rise in the number of community-acquired cases. CDI has a profound economic impact on both the healthcare system and patients, secondary to recurrences, hospitalization, prolonged length of stay, cost of treatment, and indirect societal costs. With emergence of newer treatment options, the standard of care is shifting from metronidazole and vancomycin towards fidaxomicin and fecal microbiota transplantation (FMT), which despite being more expensive, are more efficacious in preventing recurrences and hence overall are more beneficial forms of therapy per cost-effectiveness analyses. Data regarding preferred route of FMT, timing of FMT, and non-conventional therapies such as bezlotoxumab is scant. There is a need for further studies to elucidate the true attributable costs of CDI as well as continued cost-effectiveness research to reduce the economic burden associated with the disease and improve clinical practice.

Incidence of hospital-acquired influenza in adults: A prospective surveillance study from 2004 to 2017 in a French tertiary care hospital

Hospital-acquired influenza potentially leads to significant morbidity and mortality in already vulnerable patients, but its overall burden is not fully understood. We undertook this study to estimate the incidence and trends of hospital-acquired laboratory-confirmed influenza among adults, and to compare clinical characteristics between hospital-acquired and community-acquired influenza cases. This was a prospective surveillance study over 11 years of adults with influenza-like-illness (ILI) hospitalized in surgery, medicine and geriatric wards in a tertiary acute-care hospital in Lyon, France. Nasal swabs were systematically collected from those with ILI and tested for influenza by reverse transcriptase-polymerase chain reaction at the national influenza reference laboratory (Lyon, France). Influenza was laboratory confirmed at a rate of 1 in 13 patients who developed ILI during their hospitalization. Having an underlying disease was an important characteristic of hospital-acquired ILI cases. Cardiovascular disease was the most frequent underlying condition in both influenza-positive and influenza-negative patients. Complications were more frequent for influenza-positive than influenza-negative patients. The influenza incidence rate was highest in the geriatric ward and increased over the study period. Hospital-acquired influenza poses a significant risk to already vulnerable patients. Longitudinal surveillance data are essential to support better recognition and monitoring of viral infections in hospitals.

Source attribution of community-acquired cases of Legionnaires' disease-results from the German LeTriWa study; Berlin, 2016-2019.

IntroductionSources of infection of most cases of community-acquired Legionnaires’ disease (CALD) are unknown.ObjectiveIdentification of sources of infection of CALD.SettingBerlin; December 2016–May 2019.ParticipantsAdult cases of CALD reported to district health authorities and consenting to the study; age and hospital matched controls.Main outcome measurePercentage of cases of CALD with attributed source of infection.MethodsAnalysis of secondary patient samples for monoclonal antibody (MAb) type (and sequence type); questionnaire-based interviews, analysis of standard household water samples for Legionella concentration followed by MAb (and sequence) typing of Legionella pneumophila serogroup 1 (Lp1) isolates; among cases taking of additional water samples to identify the infectious source as appropriate; recruitment of control persons for comparison of exposure history and Legionella in standard household water samples. For each case an appraisal matrix was filled in to attribute any of three source types (external (non-residence) source, residential non-drinking water (RnDW) source (not directly from drinking water outlet), residential drinking water (RDW) as source) using three evidence types (microbiological results, cluster evidence, analytical-comparative evidence (using added information from controls)).ResultsInclusion of 111 study cases and 202 controls. Median age of cases was 67 years (range 25–93 years), 74 (67%) were male. Among 65 patients with urine typable for MAb type we found a MAb 3/1-positive strain in all of them. Compared to controls being a case was not associated with a higher Legionella concentration in standard household water samples, however, the presence of a MAb 3/1-positive strain was significantly associated (odds ratio (OR) = 4.9, 95% confidence interval (CI) 1.7 to 11). Thus, a source was attributed by microbiological evidence if it contained a MAb 3/1-positive strain. A source was attributed by cluster evidence if at least two cases were exposed to the same source. Statistically significant general source types were attributed by calculating the population attributable risk (analytical-comparative evidence). We identified an external source in 16 (14%) cases, and RDW as source in 28 (25%). Wearing inadequately disinfected dentures was the only RnDW source significantly associated with cases (OR = 3.2, 95% CI 1.3 to 7.8) and led to an additional 8% of cases with source attribution, for a total of 48% of cases attributed.ConclusionUsing the appraisal matrix we attributed almost half of all cases of CALD to an infectious source, predominantly RDW. Risk for LD seems to be conferred primarily by the type of Legionella rather than the amount. Dentures as a new infectious source needs further, in particular, integrated microbiological, molecular and epidemiological confirmation.

Neonatal Infection Due to SARS-CoV-2: An Epidemiological Study in Spain.

Objective: Coronavirus disease 2019 (COVID-19) cases caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue to increase worldwide. Although some data from pediatric series are available, more evidence is required, especially in neonates, a group with specific characteristics that deserve special attention. This study aimed to describe general and clinical characteristics, management, and treatment of postnatal-acquired (community and nosocomial/hospital-acquired) COVID-19 neonatal cases in Spain.Methods: This was a national prospective epidemiological study that included cases from a National Registry supported by the Spanish Society of Neonatology. Neonates with postnatal SARS-CoV-2 infection were included in this study. General data and infection-related information (mode and source of transmission, age at diagnosis, clinical manifestations, need for hospitalization, admission unit, treatment administered, and complementary studies performed, hospital stay associated with the infection) were collected.Results: A total of 40 cases, 26 community-acquired and 14 nosocomial were registered. Ten were preterm newborns (2 community-acquired and 8 nosocomial COVID-19 cases). Mothers (in both groups) and healthcare workers (in nosocomial cases) were the main source of infection. Hospital admission was required in 22 community-acquired cases [18 admitted to the neonatal intermediate care unit (NIMCU) and 4 to the neonatal intensive care unit (NICU)]. Among nosocomial COVID-19 cases (n = 14), previously admitted for other reasons, 4 were admitted to the NIMCU and 10 to the NICU. Ten asymptomatic patients were registered (5 in each group). In the remaining cases, clinical manifestations were generally mild in both groups, including upper respiratory airways infection, febrile syndrome or acute gastroenteritis with good overall health. In both groups, most severe cases occurred in preterm neonates or neonates with concomitant pathologies. Most of the cases did not require respiratory support. Hydroxychloroquine was administered to 4 patients in the community-acquired group and to 2 patients in the nosocomial group. Follow-up after hospital discharge was performed in most patients.Conclusions: This is the largest series of COVID-19 neonatal cases in Spain published to date. Although clinical manifestations were generally mild, prevention, treatment, and management in this group are essential.

Risk perception of COVID-19 pandemic among health care providers: qualitative study conducted at the King Baudoin Hospital in Guédiawaye, the first hospital faced with managing a community-acquired COVID-19 case in Senegal

health care systems in West Africa have been under strain since the beginning of the COVID-19 pandemic. The exposure of health personnel to infection during the COVID-19 pandemic has been reported in several studies. The purpose of this study was to analyze health workers' actual and perceived risk in the first hospital faced with managing a community-acquired COVID-19 case in Senegal. we conducted an exploratory descriptive study of health care providers' perception about their own risk during the COVID-19 pandemic. Forty-seven health-care providers were interviewed in personal, extensive interviews in this hospital. the fear of disease was present among the health staff. This fear was caused by several exogenous and endogenous factors, including the lack of knowledge of the virus and COVID-19 disease, the feeling of vulnerability due to insufficient availability of personal protective equipment, healthcare professionals' position in relation to the priesthood from the medical profession and the real and perceived risk of putting their family and their entourage in potentially dangerous situations. this study highlights the need for psycho-affective management of health care workers during this pandemic by taking the gender dimension into account. The provision of personal adequate protective equipment and stress management measures could enable front-line workers to cope with this pandemic in complete serenity.

Healthcare-Associated Legionnaires' Disease, Europe, 2008-2017.

Healthcare-associated Legionnaires’ disease (HCA LD) can cause nosocomial outbreaks with high death rates. We compared community-acquired LD cases with HCA LD cases in Europe during 2008−2017 using data from The European Surveillance System. A total of 29 countries reported 40,411 community-acquired and 4,315 HCA LD cases. Of the HCA LD cases, 2,937 (68.1%) were hospital-acquired and 1,378 (31.9%) were linked to other healthcare facilities. The odds of having HCA LD were higher for women, children and persons <20 years of age, and persons >60 years of age. Out of the cases caused by Legionella pneumophila with a known serotype, community-acquired LD was more likely to be caused by L. pneumophila serogroup 1 (92.3%) than was HCA LD (85.1%). HCA LD patients were more likely to die. HCA LD is associated with specific patient demographics, causative strains, and outcomes. Healthcare facilities should consider these characteristics when designing HCA LD prevention strategies.

Bacterial infections in cirrhosis: a narrative review and key points for clinical practice

Bacterial infections are frequent complications of liver cirrhosis, accounting for severe clinical courses, and increased mortality. The reduction of the negative clinical impact of infections may be achieved by a combination of prophylactic measures to reduce the occurrence, early identification, and management. Spontaneous bacterial peritonitis (SBP), urinary tract infections, pneumonia, cellulitis, and spontaneous bacteremia are frequent in cirrhosis. The choice of initial empirical antimicrobial therapy should be based on both site, severity, and origin of infection (community-acquired, nosocomial, or healthcare-associated) and on antibiotic resistance patterns. 3rd generation cephalosporins are generally indicated as empirical therapy in most community-acquired cases. However, for nosocomial and healthcare-associated infections, due to a high rate of multidrug-resistant (MDR) pathogens, a broader spectrum treatment is appropriate. In order to prevent antibiotic resistance emergence, microbiological cultures should be collected, and a de-escalation applied when antimicrobial susceptibility tests are available. Standard measures to prevent infections and the identification of carriers of MDR bacteria are essential strategies to prevent infections in cirrhosis. Antibiotic prophylaxis should be applied only to gastrointestinal bleeding, SBP recurrence prevention, and cirrhotics at high risk of a first episode of SBP.

Analysis of community-acquired COVID-19 cases in Taiwan.

The demographic characteristics and transmission dynamics of the community-acquired coronavirus disease 2019 (COVID-19) cases in Taiwan were analyzed for more effective control and prevention of the community transmission of this novel disease. Open-access data and press releases on COVID-19 in Taiwan were collected on the website of the Taiwan Centers for Disease Control. All 55 community-acquired cases of COVID-19 confirmed from January 28 to April 12, 2020, in Taiwan were included. Basic demographic characteristics, symptom presentation, infection source, route of identification, and transmission dynamics were analyzed. Of the 55 cases, 52.7% were female and 74.5% were between 20-59 years of age. One-sixth (16.4%) of community-acquired cases were asymptomatic. More than half (58.2%) of the cases were identified via contact tracing. The median incubation period was 6 days (range 1-13 d) and the median serial interval was 4 days (range -3-24 d). Twenty-six cases (47.3%) were transmitted from presymptomatic cases, 11 cases (20%) from symptomatic cases, and 2 cases (3.6%) from an asymptomatic case. The contagious period of symptomatic cases was from 7 days before to 15 days after the onset of symptoms. The high proportion of asymptomatic cases and the transmissibility in the presymptomatic and asymptomatic periods make control of COVID-19 challenging. Protective measures such as social distancing, wearing face masks, and hand washing are mandatory to prevent community transmission.

CTX-M group gene distribution of extended spectrum beta-lactamase-producing Enterobacteriaceae at a Japanese Children's hospital

Extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae have spread globally as one of the most common multidrug resistant organisms. Although a wide variety of ESBL genes were known in each geographical region, few reports existed on the distribution of ESBL genes in Japanese children. To clarify the distribution of ESBL genes, we investigated the CTX-M type of the ESBL-producing Enterobacteriaceae and patient characteristics among hospital-acquired and community-acquired cases. Total of 253 isolates of ESBL-producing Enterobacteriaceae were recovered from 238 pediatric patients. ESBL-producing Enterobacteriaceae were mostly recovered from children with underlying diseases (76.5%). Ratio of community-acquired and hospital-acquired cases was 58.8% and 41.2%, respectively. Compared to the hospital-acquired cases, community-acquired cases had younger age, fewer underlying diseases, and the dominant detection of Escherichia coli. The most common ESBL-producing Enterobacteriaceae was E. coli (79.8%), followed by Klebsiella pneumoniae (9.1%). CTX-M9 group was the most prevalent CTX-M group gene (63.2%), which was dominantly detected in E. coli (72.7%). This was the largest descriptive study to find CTX-M9 group as the most prevalent ESBL genotype among Enterobacteriaceae isolated from Japanese children in line with adult's epidemiology.

Incidence and characteristics of nosocomial influenza in a country with low vaccine coverage

Influenza vaccination coverage is low in France, in at-risk patients and in healthcare workers. We aimed to estimate the incidence of nosocomial influenza, its characteristics and outcome. During one influenza season, we retrospectively evaluated all cases of documented influenza. Inpatients with symptoms onset ≥48 h after admission were enrolled. Data were collected on a standardized questionnaire. From November 2017 to April 2018, 860 patients tested positive for influenza by polymerase chain reaction analysis on a respiratory sample. Among them, 204 (23.7%) were diagnosed ≥48 h after admission, of whom 57 (6.6% of all influenza cases) fulfilled inclusion criteria for nosocomial influenza: 26 women and 31 men, median age 82 years (interquartile range, 72.2-86.9). Twenty patients (38.6%) had recently (<6 months) received the seasonal influenza vaccine. Median time between admission and symptoms onset, and between symptoms onset and diagnosis were, respectively, 11 days (7-19.5) and 29 h (15.5-48). Influenza was mostly acquired in a double-bedded room (N= 39, 68.4%), with documented exposure in 14 cases. Influenza B virus was more common in nosocomial (46/57, 80.7%), than in community-acquired cases (359/803, 44.6%), P<0.001. Mortality rate at three months was 15.8% (N= 9). Incidence of nosocomial influenza was estimated at 0.22 per 1000 hospital-days during the study period. Nosocomial influenza is not rare in elderly inpatients, and may have severe consequences. Influenza B virus was over-represented, which suggests higher transmissibility and/or transmission clusters.

Post-Traumatic Meningitis Is a Diagnostic Challenging Time: A Systematic Review Focusing on Clinical and Pathological Features.

Post-traumatic meningitis is a dreadful condition that presents additional challenges, in terms of both diagnosis and management, when compared with community-acquired cases. Post-traumatic meningitis refers to a meningeal infection causally related to a cranio-cerebral trauma, regardless of temporal proximity. The PICO (participants, intervention, control, and outcomes) question was as follows: “Is there an association between traumatic brain injury and post-traumatic meningitis?” The present systematic review was carried out according to the Preferred Reporting Items for Systematic Review (PRISMA) standards. Studies examining post-traumatic meningitis, paying particular attention to victims of traumatic brain injury, were included. Post-traumatic meningitis represents a high mortality disease. Diagnosis may be difficult both because clinical signs are nonspecific and blurred and because of the lack of pathognomonic laboratory markers. Moreover, these markers increase with a rather long latency, thus not allowing a prompt diagnosis, which could improve patients’ outcome. Among all the detectable clinical signs, the appearance of cranial cerebrospinal fluid (CSF) leakage (manifesting as rhinorrhea or otorrhea) should always arouse suspicion of meningitis. On one hand, microbiological exams on cerebrospinal fluid (CSF), which represent the gold standard for the diagnosis, require days to get reliable results. On the other hand, radiological exams, especially CT of the brain, could represent an alternative for early diagnosis. An update on these issues is certainly of interest to focus on possible predictors of survival and useful tools for prompt diagnosis.

Phenotypic and Genomic Characterization of Virulence Heterogeneity in Multidrug-Resistant ST11 Klebsiella pneumoniae During Inter-Host Transmission and Evolution.

BackgroundMultidrug-resistant (MDR) ST11 hypervirulent Klebsiella pneumoniae (hvKp) is emerging in China.PurposeThe aim of this study was to track the transmission and evolution of hvKp.Materials and MethodsA retrospective study focused on Kp infection was conducted. Clinical data were collected from electronic medical records. Whole-genome sequencing of Kp strains was performed. Single-nucleotide polymorphisms (SNPs) were analyzed and a transmission map was constructed. Sequence type, and antimicrobial and virulence-associated genes were characterized. Strains with some combination of the virulence genes, prmpA, prmpA2, iucA, iroB, and peg-344, were defined as hvKp. Kp virulence phenotypes were evaluated using the Galleria mellonella model.ResultsAll 33 Kp strains were MDR-Kp and 13 (39.4%) were hvKp. Most hvKp strains (84.6%, 11/13) were hospital-acquired infections (HAIs). Two unique combinations of virulence-associated genes were detected among hvKp strains. Eleven cases were associated with prmpA2+iucA and two strains presented with peg-344+prmpA+prmpA2+iucA. Surprisingly, two community-acquired MDR-hvKp infection cases were identified. Eight hvKp strains (61.5%, 8/13) exhibited a hypervirulent phenotype in the G. mellonella model. Five MDR-hvKp strains with the hypervirulence phenotype originated from a single cluster. Additionally, nine clones were identified among the two clades, six of which were hvKp. Moreover, the hvKp in clade 1 carried the IncHI1B plasmid replicon, whereas none of the hvKp strains in clade 2 harbored IncHI1B. These data, showing that different hvKp clones distributed into separate clades, indicate that transmission and evolution occurred within the hospital.ConclusionDuring inter-host evolution and transmission, various virulence clusters of the epidemic clone, MDR-ST11, converged, conferring phenotypic virulence heterogeneity and spread within the hospital and possibly the community. Mobile/conjugative genetic elements associated with virulence-encoding gene clusters might emerge and have been transmitted within the hospital, suggesting that enhanced ongoing surveillance is essential.

Antimicrobial Resistance and Pathogenicity Determination of Community-Acquired Hypervirulent Klebsiella pneumoniae.

Hypervirulent Klebsiella pneumoniae (hvKp) can cause severe invasive infections in healthy and immunocompromised individuals. However, there is still lack of a consensus definition of hvKp. In this study, we solely focused on the clinical isolates cultured from subcutaneous drainage of community-acquired liver abscess cases, and an hvKp strain was defined on the basis of co-harboring virulence gene regulator of mucoid phenotype A (rmpA)/rmpA2, iucA, iroB, and peg-344. A total of 47 nonrepetitive hvKp isolates were collected from January 2015 to December 2017 in a tertiary teaching hospital in Shanghai, China. All isolates were susceptible to the commonly used antibiotics. Only one strain (RJ-Kp24) had the positive detection of blaCTX-M-14 and was resistant to ceftazidime, cefotaxime, and cefepime. S1-pulsed-field gel electrophoresis (PFGE) and southern hybridization confirmed the presence of a roughly 90 kb blaCTX-M-14-carrying plasmid and a roughly 240 kb virulence plasmid. Further analysis revealed that ST23 (n = 17) sequence type and K1 (n = 20) and K2 (n = 9) serotypes were dominant in hvKp, while only 31.9% (15/47) and 46.8% (22/47) of hvKp isolates displayed hypermucoviscosity and resistance to serum killing, respectively. For further evaluation of the pathogenicity of hvKp, six representative strains were randomly selected. Three strains, RJ-Kp10, RJ-Kp28, and RJ-Kp31, displayed a remarkable resistance to serum killing and neutrophil phagocytosis. Mouse lethality assay revealed that these strains had the 50% lethal dose (LD50) of 102-103 cell forming unit (CFU), while others had the LD50 of 104-105 CFU. These results demonstrated that strain virulence differed significantly within these defined hvKp. The convergence of multidrug resistance and enhanced virulence in K. pneumoniae has presented a major infection control challenge.