Non-bacterial Pathogens Research Articles

Demographic and Clinical Factors Associated with Bacterial or Nonbacterial Etiologies of Acute Undifferentiated Febrile Illness: Findings from a 3-Year Observational Study in Thailand, 2017-2020.

Acute undifferentiated febrile illness (AUFI) is often undiagnosed in Thailand, resulting in delayed or ineffective treatment. We compared the demographic, exposure history, and clinical characteristics of AUFI patients with laboratory evidence of bacterial and nonbacterial pathogens. Patients aged 2-80 years presenting to 12 hospitals in Nakhon Phanom and Tak provinces were enrolled from April 2017 through May 2020. Interviews were conducted and blood, urine, and sputum were collected for culture as well as rapid diagnostic and molecular testing. A total of 1,263 patients tested positive for one or more bacterial, viral, or parasitic pathogens and were included in the analysis. Multivariable logistic regression was performed to compare factors associated with bacterial infections versus nonbacterial infections. Bacterial infections were more commonly identified in participants from Nakhon Phanom than Tak. Bacterial infections were independently associated with several factors including age ≥50 years (adjusted odds ratio [95% CI]): (4.18 [2.85-6.14]), contact with farm animals (1.82 [1.29-2.57]), antibiotic use within 72 hours of hospital presentation (2.37 [1.50-3.74]), jaundice (2.31 [1.15-4.63]), existing comorbidities (2.77 [1.93-3.96]), contact with febrile individuals (0.42 [0.31-0.57]), muscle pain (0.44 [0.31-0.64]), and rash (0.45 [0.29-0.70]). Bacterial infections were also associated with longer hospitalization (2.75 [2.08-3.64]) and lower odds of recovery at the time of discharge (0.14 [0.07-0.31]). Consideration of patient characteristics and signs/symptoms may help to inform targeted laboratory testing for suspected infectious etiologies. Understanding factors associated with bacterial and non-bacterial causes of AUFI may aid diagnosis and judicious use of antibiotics in resource-limited settings.

Polymicrobial brain abscesses: A complex condition with diagnostic and therapeutic challenges.

Brain abscesses (BA) are focal parenchymal infections that remain life-threatening conditions. Polymicrobial BAs (PBAs) are complex coinfections of bacteria or bacterial and nonbacterial pathogens such as fungi or parasites, with diagnostic and therapeutic challenges. In this article, we comprehensively review the prevalence, pathogenesis, clinical manifestations, and microbiological, histopathological, and radiological features of PBAs, as well as treatment and prognosis. While PBAs and monomicrobial BAs have some similarities such as nonspecific clinical presentations, PBAs are more complex in their pathogenesis, pathological, and imaging presentations. The diagnostic challenges of PBAs include nonspecific imaging features at early stages and difficulties in identification of some pathogens by routine techniques without the use of molecular analysis. Imaging of late-stage PBAs demonstrates increased heterogeneity within lesions, which corresponds to variable histopathological features depending on the dominant pathogen-induced changes in different areas. This heterogeneity is particularly marked in cases of coinfections with nonbacterial pathogens such as Toxoplasma gondii. Therapeutic challenges in the management of PBAs include initial medical therapy for possibly underrecognized coinfections prior to identification of multiple pathogens and subsequent broad-spectrum antimicrobial therapy to eradicate identified pathogens. PBAs deserve more awareness to facilitate prompt and appropriate treatment.

The non-bacterial pathogenic and clinical characteristics of acute respiratory tract infection in children in a hospital of pediatric in Sichuan Province from 2019 to 2021

Objective: To explore the non-bacterial pathogen distribution, epidemiological characteristics, and clinical features of acute respiratory infections in children in Sichuan Province. Methods: Using a retrospective cohort study method, this study selected hospitalized children diagnosed with acute respiratory infections at West China Second Hospital of Sichuan University from February 2019 to January 2021, and tested 13 pathogens using polymerase chain reaction (PCR)-fragment analysis. The children were divided into infant group (<1 year old), toddler group (1 year old ≤ age <3 years old), preschool group (3 years old ≤ age <6 years old) and school-age group (6 years old ≤ age <18 years old). The distribution of pathogen positive rates, seasonal epidemic characteristics, clinical characteristics, and some laboratory test indicators were analyzed in children. Statistical analysis was performed on the results using SPSS 22.0 software, with count data expressed as percentages and inter group comparisons using SPSS 22.0 software χ2 Inspection. Results: A total of 2 922 pediatric patients were included in this study, with 1 748 (59.8%) positive for pathogens detected. Among them, 1 391 (79.6%) were detected as a single pathogen, and 357 (20.4%) were detected as a mixture of two or more pathogens. The most commonly detected pathogens were rhinovirus (HRV) (39.7%), syncytial virus (RSV) (22.8%), and parainfluenza virus (PIV) (12.5%). Pathogen positivity is more common in children under 6 years old (χ2=146.59, P<0.001), with a slightly higher positivity rate in male children (61.3%, 1 047/1 707) than in female children (57.7%, 701/1 215) (χ2=3.91, P=0.048), and compared with pathogen negative children, positive children are more prone to symptoms such as cough, wheezing, and shortness of breath (χ2=259.15, 366.06, 12.48, P<0.001). The distribution of different pathogens varies among children of different age groups, and HRV is more common in children aged 1-3 and 3-6 years old (χ2=9.74, P<0.001), while RSV is more common in children under 1 year old (χ2=178.63, P<0.001), while mycoplasma pneumoniae (MP) and influenza virus (InfA/B) are less common in children under 1 year old (χ2=92.54, 12.90,22.21, P<0.01). The prevalence of multiple pathogens showed seasonal changes. HRV showed a high prevalence trend in spring and autumn, while the prevalence of RSV infection was mainly seen in autumn and winter festivals. The positive rate of different pathogens after the outbreak of novel coronavirus pneumonia was significantly lower than that before the outbreak (χ2=252.68, P<0.001). Conclusion: The detection rate of non-bacterial respiratory pathogens in children in Sichuan Province from 2019 to 2021 is high, which is prone to symptoms such as cough, wheezing, and shortness of breath, with HRV and RSV being the main types. The positive rate of respiratory pathogens varies among different age groups, genders, and seasons.

Distribution of non-bacterial pathogens in 1 788 children with community-acquired pneumonia

To investigate the distribution characteristics of non-bacterial pathogens in community-acquired pneumonia (CAP) in children. A total of 1 788 CAP children admitted to Shenyang Children's Hospital from December 2021 to November 2022 were selected. Multiple RT-PCR and capillary electrophoresis were used to detect 10 viral pathogens and 2 atypical pathogens, and serum antibodies of Chlamydial pneumoniae (Ch) and Mycoplasma pneumoniae (MP) were detected. The distribution characteristics of different pathogens were analyzed. Among the 1 788 CAP children, 1 295 children were pathogen-positive, with a positive rate of 72.43% (1 295/1 788), including a viral pathogen positive rate of 59.68% (1 067/1 788) and an atypical pathogen positive rate of 22.04% (394/1 788). The positive rates from high to low were MP, respiratory syncytial virus (RSV), influenza B virus (IVB), human metapneumovirus (HMPV), human rhinovirus (HRV), human parainfluenza virus (HPIV), influenza A virus (IVA), bocavirus (BoV), human adenovirus (HADV), Ch, and human coronavirus (HCOV). RSV and MP were the main pathogens in spring; MP had the highest positive rate in summer, followed by IVA; HMPV had the highest positive rate in autumn; IVB and RSV were the main pathogens in winter. The positive rate of MP in girls was higher than that in boys (P<0.05), and there were no significant differences in other pathogens between genders (P>0.05). The positivity rates of certain pathogens differed among age groups (P<0.05): the positivity rate of MP was highest in the >6 year-old group; the positivity rates of RSV and Ch were highest in the <1 year-old group; the positivity rates of HPIV and IVB were highest in the 1 to <3 year-old group. RSV, MP, HRV, and HMPV were the main pathogens in children with severe pneumonia, while MP was the primary pathogen in children with lobar pneumonia, and MP, IVB, HMPV, RSV, and HRV were the top 5 pathogens in acute bronchopneumonia. MP, RSV, IVB, HMPV, and HRV are the main pathogens of CAP in children, and there are certain differences in the positive rates of respiratory pathogens among children of different ages, genders, and seasons.

A scoping review of the testing of bulk tank milk to detect nonbacterial pathogens or herd exposure to nonbacterial pathogens in dairy cattle

In this scoping review, we characterized the literature reporting on the testing of bulk milk samples to detect microorganisms other than bacteria that can cause diseases in dairy cattle, including viruses, helminths, algae, and protozoa. A search strategy was completed by screening databases, conference proceedings, animal health agency websites, disease surveillance program websites, and handbooks of cattle-related diagnostic tests for potentially relevant articles. Two reviewers independently screened articles in English, Portuguese, or Spanish; original studies reporting on the testing of farm-level, unprocessed bulk milk samples for presence of pathogens or specific antibodies against agents other than bacteria that can cause diseases in cows were retained. From all studies, we used spreadsheets to extract relevant information, including pathogen screened, test used, and country of origin of bulk milk samples. Additionally, for studies reporting sufficient data to estimate test characteristics, we extracted detailed information about herd eligibility, testing protocol, and herd-level infection definition. A total of 8,829 records were identified, from which 1,592 were retained and assessed for eligibility, and 306 were included. Bovine viral diarrhea virus, Fasciola hepatica, Ostertagia ostertagi, and bovine herpesvirus 1 were the most frequently screened agents, reported from 107, 45, 45, and 33 studies, respectively. Sensitivity of bulk milk ELISA to detect herds with animals infected by bovine herpesvirus 1 ranged from 2 to 100%, and was affected mostly by antigen selection, cut-off adopted, herd vaccination status, and seroprevalence of lactating cows. Bulk milk ELISA had very high specificity to detect herds free of bovine leukemia virus, and varying sensitivity to detect herds with infected animals, which depended on the within-herd seroprevalence of lactating cattle. As for bovine viral diarrhea virus, in general, the sensitivity of bulk milk ELISA was moderate to high (>80%) when infection status was defined based on presence of persistently infected cattle or a high proportion of seropositive lactating cattle. Nevertheless, bulk milk ELISA was not able to distinguish infected and noninfected herds based on presence of seropositive unvaccinated weanlings. The PCR or quantitative PCR protocols employed had very low sensitivities (<40%) and very high specificities (>95%) to classify bovine viral diarrhea virus infection status of dairy herds. Sensitivity and specificity of bulk milk ELISA to classify herds with regards to presence of F. hepatica- or O. ostertagi-parasitized cattle were generally high and driven mostly by the definition of herd infection status. Conversely, bulk milk ELISA demonstrated varying characteristics to detect herds with or without Dictyocaulus viviparus-parasitized cattle, depending primarily on the antigen selected and presence of cattle with clinical signs of lungworm infection.

Searching for a Reliable Viral Indicator of Faecal Pollution in Aquatic Environments.

The disposal of sewage in significant quantities poses a health hazard to aquatic ecosystems. These effluents can contain a wide range of pathogens, making faecal contamination a leading source of waterborne diseases around the world. Yet monitoring bacteria or viruses in aquatic environments is time consuming and expensive. The standard indicators of faecal pollution all have limitations, including difficulty in determining the source due to lack of host specificity, poor connection with the presence of non-bacterial pathogens, or low environmental persistence. Innovative monitoring techniques are sorely needed to provide more accurate and targeted solutions. Viruses are a promising alternative to faecal indicator bacteria for monitoring, as they are more persistent in ambient water, more abundant in faeces, and are extremely host-specific. Given the range of viruses found in diverse contexts, it is not easy to find one "ideal" viral indicator of faecal pollution; however, several are of interest. In parallel, the ongoing development of molecular techniques coupled with metagenomics and bioinformatics should enable improved ways to detect faecal contamination using viruses. This review examines the evolution of faecal contamination monitoring with the followingaims (i) to identify the characteristics of the main viral indicators of faecal contamination, including human enteric viruses, bacteriophages, CRESS and plant viruses, (ii) to assess how these have been used to monitor water pollution in recent years, (iii) to evaluate the reliability of recent detection methods of such viruses, and (iv) to tentatively determine which viruses may be most effective as markers of faecal pollution.

Nonbacterial Microflora in Wastewater Treatment Plants: an Underappreciated Potential Source of Pathogens.

Wastewater treatment plants (WWTPs) receive and treat large volumes of domestic, industrial, and urban wastewater containing pathogenic and nonpathogenic microorganisms, chemical compounds, heavy metals, and other potentially hazardous substances. WWTPs play an essential role in preserving human, animal, and environmental health by removing many of these toxic and infectious agents, particularly biological hazards. Wastewater contains complex consortiums of bacterial, viral, archaeal, and eukaryotic species, and while bacteria in WWTP have been extensively studied, the temporal and spatial distribution of nonbacterial microflora (viruses, archaea, and eukaryotes) is less understood. In this study, we analyzed the viral, archaeal, and eukaryotic microflora in wastewater throughout a treatment plant (raw influent, effluent, oxidation pond water, and oxidation pond sediment) in Aotearoa (New Zealand) using Illumina shotgun metagenomic sequencing. Our results suggest a similar trend across many taxa, with an increase in relative abundance in oxidation pond samples compared to influent and effluent samples, except for archaea, which had the opposite trend. Additionally, some microbial families, such as Podoviridae bacteriophages and Apicomplexa alveolates, appeared largely unaffected by the treatment process, with their relative abundance remaining stable throughout. Several groups encompassing pathogenic species, such as Leishmania, Plasmodium, Toxoplasma, Apicomplexa, Cryptococcus, Botrytis, and Ustilago, were identified. If present, these potentially pathogenic species could be a threat to human and animal health and agricultural productivity; therefore, further investigation is warranted. These nonbacterial pathogens should be considered when assessing the potential for vector transmission, distribution of biosolids to land, and discharge of treated wastewater to waterways or land. IMPORTANCE Nonbacterial microflora in wastewater remain understudied compared to their bacterial counterparts despite their importance in the wastewater treatment process. In this study, we report the temporal and spatial distributions of DNA viruses, archaea, protozoa, and fungi in raw wastewater influent, effluent, oxidation pond water, and oxidation pond sediments by using shotgun metagenomic sequencing. Our study indicated the presence of groups of nonbacterial taxa which encompass pathogenic species that may have potential to cause disease in humans, animals, and agricultural crops. We also observed higher alpha diversity in viruses, archaea, and fungi in effluent samples than in influent samples. This suggests that the resident microflora in the wastewater treatment plant may be making a greater contribution to the diversity of taxa observed in wastewater effluent than previously thought. This study provides important insights to better understand the potential human, animal, and environmental health impacts of discharged treated wastewater.

Loss-of-function mutations in WRKY22 and WRKY25 impair stomatal-mediated immunity and PTI and ETI responses against Pseudomonas syringae pv. tomato.

Plants defend themselves against pathogens using a two-layered immune system. The first response, pattern-triggered immunity (PTI), is activated upon recognition of microbe-associated molecular patterns (MAMPs). Virulent bacteria such as Pseudomonas syringae pv. tomato (Pst), deliver effector proteins into the plant cell to promote susceptibility. However, some plants possess resistance (R) proteins that recognize specific effectors leading to the activation of the second response, effector-triggered immunity (ETI). Resistant tomatoes such as Río Grande-PtoR recognize two Pst effectors (AvrPto and AvrPtoB) through the host Pto/Prf complex and activate ETI. We previously showed that the transcription factors (TF) WRKY22 and WRKY25 are positive regulators of plant immunity against bacterial and potentially non-bacterial pathogens in Nicotiana benthamiana. Here, the CRISPR-Cas9 technique was used to develop three knockout tomato lines for either one or both TFs. The single and double mutants were all compromised in Pto/Prf-mediated ETI and had a weaker PTI response. The stomata apertures in all of the mutant lines did not respond to darkness or challenge with Pst DC3000. The WRKY22 and WRKY25 proteins both localize in the nucleus, but we found no evidence of a physical interaction between them. The WRKY22 TF was found to be involved in the transcriptional regulation of WRKY25, supporting the idea that they are not functionally redundant. Together, our results indicate that both WRKY TFs play a role in modulating stomata and are positive regulators of plant immunity in tomato.

The Use of Antibiotics without a Prescription : a Literature Review

Background : Infectious diseases are treated with antibiotics. Antibiotics are widely used because infectious diseases are so common. Even though antibiotics are purchased at pharmacies with a doctor's prescription, many antibiotics are currently being taken without a prescription. Resistance will develop if antibiotics are consumed without a doctor's prescription and not according to indications for administration. Objective : This study examines how people use antibiotics without a doctor's prescription. Methods : The author of this article uses a method related to the article's title by using some relevant literature from database of journals such as Google Scholar. The discussion and findings of this study will assist readers and health professionals in analyzing how people use antibiotics without a prescription. Result : Based on the findings of the five studies, journals discuss the relationship between knowledge level and attitudes regarding the use of antibiotics without a prescription. This literature review shows that most people of reproductive age consume antibiotics without a doctor's prescription to treat symptoms usually caused by non-bacterial pathogens. Conclusion : . One of the intervention approaches taken to restrict access is government control. Holistic interventions against those who sell antibiotics without a prescription are expected to significantly reduce the irresponsible use of antibiotics in the community

Analysis of non-bacterial respiratory pathogens in children in Ningbo City from 2019 to 2021

Objective: To investigate the distribution characteristics of respiratory non-bacterial pathogens in children in Ningbo from 2019 to 2021. Methods: A retrospective analysis was performed on 23 733 children with respiratory tract infection who visited the department of pediatrics of Ningbo Women and Children's Hospital from July 2019 to December 2021. There were 13 509 males (56.92%) and 10 224 females (43.08%), with an age range of 1 day to 18 years old. There were 981 cases in the neonatal group (younger than 1 month old), 5 880 cases in the infant group (1 month to younger than 1 year old), 6 552 cases in the toddler group (1 to younger than 3 years old), 7 638 cases in the preschool group (3 to younger than 7 years old), and 2 682 cases in the school-age group (7 to 18 years old). Thirteen respiratory pathogens were detected by multiple polymerase chain reaction (PCR) based on capillary electrophoresis, and SPSS 23.0 software was used for statistical analysis of the results, the count data were expressed as percentages, and the χ2 test was used for comparison between groups. Results: Of the 23 733 specimens, 13 330 were positive for respiratory pathogens, with a total positive rate of 56.17%. The positive rates of human rhinovirus (HRV) 24.05% (5 707/23 733), human respiratory syncytial virus (HRSV) 10.45% (2 480/2 3733) and mycoplasma pneumoniae (Mp) 7.03% (1 668/23 733) were in the first three. The positive rates of pathogens in the male and female children were 57.47% (7 763/13 509) and 54.45% (5 567/10 224), respectively, and the difference was statistically significant (χ2=21.488, P<0.001). The positive rates in the neonatal group, infant group, toddler group, preschool group, and school-age group were 31.80% (312/981), 54.71% (3 217/5 880), 63.23% (4 143/6 552), 59.83% (4 570/7 638), 40.57% (1 088/2 682), respectively, and the difference among the groups was statistically significant (χ2=681.225, P<0.001). The single infection rate was 47.43% (11 256/23 733), the mixed infection rate of two or more pathogens was 8.74% (2 074/23 733), most of which were mixed infections of two pathogens. HRV, HADV, HCOV, Ch disseminated in the whole year. HRSV, HMPV, Boca, HPIV occurred mostly in fall and winter. The positive rates of FluA, FluB, Mp were at a low level after the corona virus disease 2019 (COVID-19) epidemic (2020 and 2021). The positive rates of FluA, H1N1, H3N2, FluB, HADV, Mp in 2020 were significantly lower than in 2019 (P<0.05). The positive rates of HPIV, HRV, HCOV, Ch in 2020 were significantly higher than in 2019 (P<0.05). The positive rates of FluA, H1N1, H3N2, HPIV, HCOV, Mp, Ch in 2021 were significantly lower than in 2020 (P<0.05). The positive rates of Boca, HMPV, HRSV in 2021 were significantly higher than in 2020 (P<0.05). Conclusion: From 2019 to 2021, the main non-bacterial respiratory pathogens of children in Ningbo City were Mp and HRV, and the detection rates of respiratory pathogens varied among different ages, seasons and genders.

A Broad-Range Disposable Electrochemical Biosensor Based on Screen-Printed Carbon Electrodes for Detection of Human Noroviruses.

Human noroviruses (HuNoVs) are the major non-bacterial pathogens causing acute gastroenteritis in people of all ages worldwide. No stable culture system in vitro is available for routing the detection of multiple strains of HuNoVs. A simple and rapid method for detection of HuNoVs is of great significance for preventing and controlling this pathogen. In this work, an electrochemical biosensor for sensitive and fast detection of HuNoVs was constructed based on a screen-printed carbon electrode (SPCE). Gold nanoparticles and protein-A were applied on the SPCE surface for enhancement of the electrical signals and the linkage of antibodies with a fixed orientation, respectively. A monoclonal antibody (MAb) against the S domain protein of the viral capsid (VP1) was further immobilized on the SPCE to bind HuNoVs specifically. The binding of VP1 to the coated MAbs resulted in the reduction of conductivity (current) measured by cyclic voltammetry (CV) and differential pulse voltammetry (DPV). The reduction in the current was correlated to the concentration of VP1/HuNoVs. The detection limitation of Genogroup I.1 (GI.1) VP1 and Genogroup II.4 (GII.4) VP1 was 0.37 ng/ml (≈1.93×107 HuNoVs/mL) and 0.22 ng/ml (≈1.15×107 HuNoVs/mL), respectively. The detection limitation of both GI and GII HuNoVs in clinical fecal samples was 104 genomic copies/mL. The results could be obtained in 1 h. We demonstrated that this disposable electrochemical biosensor was a good candidate for rapid detection of different genogroup and genotype HuNoVs.

Detection of Enteric Viruses from Wastewater and River Water in Botswana.

Waterborne diseases remain a public health concern in developing countries where many lack access to safe water. Water testing mainly uses bacterial indicators to assess water quality, which may not fully indicate the threat from other non-bacterial pathogens like enteric viruses. This study was done to ascertain and establish the viral load, the temporal and spatial distribution of rotavirus A and norovirus (GI and GII) in sewage and river water samples. A total of 45 samples of raw and treated sewage, and surface water, were collected from a sludge activated wastewater treatment plant in Gaborone, and after treatment from the Notwane River, Botswana, over a period of 9months (February 2016 to October 2016). Viruses were concentrated using polyethylene glycol/NaCl precipitation. Virus detection was performed using real-time polymerase chain reaction (RT-PCR). Rotavirus A was the most prevalent (84.4% positive samples), followed by Norovirus GI (48.9% positive samples), and Norovirus GII 46.7% positive samples). Detected viral loads went up to 104 genome copies per liter (copies/L) for all the viruses. The enteric viruses were detected in all the study sites with highest detection from site S1 (inlet). There was no significant association between physicochemical parameters and viral loads, except for pH which showed significant relationship with rotavirus and norovirus GII (p ≤ 0.05). This is the first study in Botswana to highlight the occurrence and quantification of the enteric viruses in treated and untreated wastewater, as well as surface water.

198. Comparison of Antibiotic Treatment Durations for Symptomatic Bacteriuria in Veterans with Spinal Cord Injuries or Disorders (SCI/D)

BackgroundIt is unclear based on published literature whether shorter courses of antibiotic treatment may be appropriate for urinary tract infections (UTI) in patients with SCI/D given their complex baseline clinical status. MethodsThis retrospective cohort study was conducted at the VA San Diego Healthcare System (VASDHS), which has a dedicated SCI/D unit. Adults with SCI/D were identified for inclusion if they had received antibiotics for a positive urine culture in conjunction with UTI symptoms from 1/2018-12/2020. Individual UTI events were excluded if associated with potential sources of harbored infection, anatomic abnormalities increasing risk of bacteriuria, non-bacterial pathogens, concurrent infections prolonging antibiotic treatment, or antibiotic courses managed outside of VASDHS. Treatment groups comprised UTI events treated with no more than 7 days of antibiotics (group 1) versus more than 7 days (group 2). Study endpoints were recurrence or new incidence of UTI within 30 and 90 days after completion of antibiotic treatment and onset of C. difficile infection or death within 30 or 90 days, respectively, after treatment completion. Statistical tests included Chi-square, Mann-Whitney U, and logistic regression. ResultsOne-hundred and seven patients with 241 unique UTI events were included in this study, with 79 events in group 1 and 162 events in group 2. Baseline characteristics were similar across both groups, aside from a higher incidence of hospital admission and more severe SCI/D based on the American Spinal Cord Injury Association (ASIA) impairment scale in group 2. Efficacy outcomes are described in Table 1. No deaths occurred within 90 days of treatment completion, and C. difficile infection occurred in 1 patient in group 2 after 3 days of antibiotic therapy. Duration of antibiotic therapy was not predictive of treatment failure within 30 days of antibiotic completion. Factors predictive of treatment with longer courses of antibiotic therapy included hospital admission and more severe ASIA impairment scale score. Table 1. Incidence of UTI after antibiotic completion ConclusionThe findings of this study suggest that for some patients with SCI/D, UTI treatment lasting 7 days or fewer may be effective compared to longer courses of antibiotics and could be beneficial in reducing collateral damage from antibiotic use. Disclosures All Authors: No reported disclosures

Evaluation of Activated Charcoal as an Alternative to Antimicrobials for the Treatment of Neonatal Calf Diarrhea.

PurposeNeonatal calf diarrhea (NCD) is a major cause of death and economic loss in the cattle industry. Although NCD is caused by a variety of nutritional factors and non-bacterial pathogens, treatment typically includes systemic antimicrobial therapy, even for non-severe cases that are more likely to have non-bacterial causes. Novel, non-antimicrobial therapies are needed to reduce antimicrobial use and optimize production efficiency.MethodsThis production-level study compared the efficacy of activated charcoal to that of an antimicrobial regimen for treating mild-to-moderate cases of NCD, and identified the most common etiological agents. Calves diagnosed with non-severe diarrhea were randomly allocated into 3 treatment groups (n = 86 per group): group A received a standard antimicrobial regimen, B received both antimicrobials and activated charcoal, and C received activated charcoal only. Animals were monitored over the course of 7 days for mortality and recovery from diarrhea. Fecal samples were collected upon enrollment (day 0) and on day 7 to assess the presence of major NCD-causing pathogens.ResultsMortality was higher for groups B and C relative to A, although this difference was only statistically significant for group B vs A. No significant difference in the number of recovered animals was observed among the treatment groups, although group C was significantly slower to recover than A or B. The vast majority of day 0 samples were positive for non-bacterial organisms (mainly rotavirus and Cryptosporidium parvum), which decreased significantly by day 7 regardless of treatment group.ConclusionAntimicrobials only moderately improved outcomes for non-severe diarrhea cases relative to activated charcoal. Thus, systemic antimicrobial treatment is likely unnecessary for the majority of NCD cases and should be limited to severe cases.

Accessory Genomic Epidemiology of Cocirculating Acinetobacter baumannii Clones.

ABSTRACTAcinetobacter baumannii has become one of the most important multidrug-resistant nosocomial pathogens all over the world. Nonetheless, very little is known about the diversity of A. baumannii lineages coexisting in hospital settings. Here, using whole-genome sequencing, epidemiological data, and antimicrobial susceptibility tests, we uncover the transmission dynamics of extensive and multidrug-resistant A. baumannii in a tertiary hospital over a decade. Our core genome phylogeny of almost 300 genomes suggests that there were several introductions of lineages from international clone 2 into the hospital. The molecular dating analysis shows that these introductions happened in 2006, 2007, and 2013. Furthermore, using the accessory genome, we show that these lineages were extensively disseminated across many wards in the hospital. Our results demonstrate that accessory genome variation can be a very powerful tool for conducting genomic epidemiology. We anticipate future studies employing the accessory genome along with the core genome as a powerful phylogenomic strategy to track bacterial transmissions over very short microevolutionary scales.IMPORTANCE Whole-genome sequencing for epidemiological investigations (genomic epidemiology) has been of paramount importance to understand the transmission dynamics of many bacterial (and nonbacterial) pathogens. Commonly, variation in the core genome, single nucleotide polymorphisms (SNPs), is employed to carry out genomic epidemiology. However, at very short periods of time, the core genome might not have accumulated enough variation (sufficient SNPs) to tell apart isolates. In this scenario, gene content variation in the accessory genome can be an option to conduct genomic epidemiology. Here, we used the accessory genome, as well as the core genome, to uncover the transmission dynamics of extensive and multidrug-resistant A. baumannii in a tertiary hospital for a decade. Our study shows that accessory genome variation can be a very powerful tool for conducting genomic epidemiology.

In vitro Assessment of Antimicrobial Susceptibility Patterns in Positive Blood Cultures of 22 Neonates with Neonatal Sepsis in a Children's Hospital in Baghdad

Introduction: neonatal sepsis (NS) is a serious disease in neonatology responsible for the higher percentage of neonatal deaths. It is a microbial disease caused by various types of bacterial and nonbacterial pathogens. Objectives: The objective is to determine the causative bacterial pathogens of NS for the specified period and their susceptibility toward the available antimicrobial drugs. Patients and Methods: Blood cultures of 67 neonates with clinical picture of NS were assessed for antimicrobial sensitivity. Results: Forty three cultures (64.2%) were negative, 4 cultures (5.9%) revealed Candida spp. and 20 (29.9%) cultures were positive. Gram-negative bacteria Klebsiella was the predominant pathogen causing NS (45.45%) followed be Gram-positive Staphylococcus aureus (18.2%). Vancomycin, ciprofloxacin, and amikacin were the most effective antimicrobials against Gram-positive isolates while imipenem was the most effective against Gram-negative bacteria. Discussion: klebsiella was the predominant microbe in NS in many studies, other pathogens were variable between countries. Vancomycin and imipenem approved their excellent effects reported in many others studies while penicillin approved high bacterial resistance recorded previously. Conclusion: Gram-negative bacteria were predominant and more resistant to the tested antimicrobials. Imipenem, vancomycin, ciprofloxacin were the best effective according to the isolated microbes.

A Multicenter Comparison of Rates of Central Venous Catheter-Associated Bloodstream Infections By Central Venous Catheter Type Among Pediatric Patients Receiving Treatment for Newly Diagnosed Acute Myeloid Leukemia

▪Therapy for pediatric acute myeloid leukemia (AML) requires long term central vascular access, which puts patients at risk for central line-associated bloodstream infections and their associated morbidity and mortality. Options for central venous catheter (CVC) access include tunneled external catheters, implanted ports, or peripherally inserted central catheters (PICC). Multiple studies provide conflicting reports on which CVC type is least likely to be associated with bloodstream infections in pediatric hematology-oncology patients. This multicenter cohort of pediatric AML patients is the first to investigate the course-specific incidence of positive CVC blood cultures by line type.The study included patients receiving frontline chemotherapy for AML between 1/1/2012 and 6/30/2017 at 12 US institutions. Trained personnel completed manual chart abstraction from 12/1/2015 to 07/15/2017 to obtain information on demographics, diagnosis, treatment, antibacterial prophylaxis, CVC type at the start of each course, neutropenia duration, and blood culture results obtained from CVC. Abstractors followed a standardized protocol and were required to achieve >95% concordance with trainer before starting formal chart review.Course-specific follow-up began the first day absolute neutrophil count (ANC) fell below 200 cells/uL and continued to the earliest of first positive CVC culture (overall and separately for gram-positive and gram-negative species), ANC recovery, start of conditioning for stem cell transplant, relapse, death or start of next course. Per National Healthcare Safety Network guidance, common commensals were not considered true events with the exception of viridans group streptococci (VGS). Nonbacterial pathogens were also excluded. Covariate distributions were compared by CVC type using chi-square tests. Variability in CVC type by site was examined graphically. Incidence rates for CVC positive blood cultures were reported by line type as per 1000 neutropenic days. Multivariate Poisson regression with log of neutropenia duration as offset was used to compute adjusted rate ratios (aIRR) comparing rates of positive CVC blood cultures by line type, controlling for covariates itemized in Table 1. General estimating equation methods were used to account for non-independence of observations from patients from the same institution.The study population included 357 patients who received 1,164 chemotherapy courses. Median course duration was 38 days (IQR: 34-44) with a median neutropenia duration of 19 days (IQR: 14-25). CVC were present in all patients at the start of each course, with the exception of 11 (3.3%) patients lacking a CVC at the start of Induction I. While tunneled CVC were most prevalent representing 59.1% of courses, PICC and implanted ports were utilized in 28.9% and 11.6% of courses, respectively. There was considerable variation in the distribution of CVC type by treating institution (Figure 1). Age, race, and ethnicity distributions varied by line type (Table 1). Antibacterial prophylaxis was utilized in 47% of courses.In total, there were 300 (25.8%) courses in 199 (55.7%) patients complicated by a positive CVC blood culture during the neutropenic period. The overall incidence rate of positive CVC blood cultures was 6.5 per 1000 neutropenic days. Rates increased over the course of frontline treatment from 3.1 per 1000 neutropenic days in Induction I to 9.6 per 1000 neutropenic days in Intensification II. The rate of gram-positive events (4.2 per 1000 neutropenic days) was higher than gram-negative events (2.0 per 1000 neutropenic days). The most common isolated organisms were VGS at 57.3% and less than 1% of events were polymicrobial infections. Overall rates of positive CVC blood cultures were higher for PICC relative to tunneled CVC (aIRR=1.19, 95% CI: 1.02, 1.38), while rates for implanted ports and tunneled CVC were similar (aIRR=1.06, 95% CI: 0.75, 1.51).While bacteremia is an expected complication during post-chemotherapy neutropenia and not always due to the presence of a CVC, the risk for a positive CVC blood culture is significantly increased for children with PICC compared with those with tunneled CVC or implanted port. Also, the risk was higher after Induction I and increased with age. Given the notable practice variation in line choice, these data highlight an opportunity for standardization with a goal to reduce infectious complications. [Display omitted] DisclosuresFisher:Pfizer: Research Funding; Merck: Research Funding. Gramatges:Bristol Meyer Squibb: Research Funding.

Antibiotic use practices of veterinarians and para-veterinarians and the implications for antibiotic stewardship in Nigeria.

The aim of this study was to describe the antibiotic use practices of veterinarians and para-veterinarians in Nigeria. An online survey was distributed during November through December 2018 via email and phone to veterinarians and para-veterinarians to collect information on antibiotic use practices. Data were downloaded into Excel and descriptive statistics were presented and analysed. The survey was completed by 390 respondents. Almost all respondents (98.5%, 384/390) recommended the use of antibiotics to treat animal patients, and of these, 93.2% (358/384) were veterinarians and 6.8% (26/384) were para-veterinarians. Most respondents reported commonly recommending the use of oxytetracycline (82.6%, 317/384), tylosin (44.5%, 171/384) and gentamycin (43.8%, 168/384). A third (32.0%, 122/384) of respondents did not undertake antimicrobial susceptibility testing (AST) prior to antibiotic treatment. At least 60% of the respondents recommended the use of antibiotics for the treatment of non-bacterial pathogens, including viral, helminth and fungal pathogens. Over 55% (217/390) were not aware of government-issued guidelines on antibiotic use in animals, although of those aware, 69% (74/107) utilised the guidelines. Across all respondents, the majority believed legislation or regulation by government can influence the use of antibiotics by animal health professionals. The study highlights areas that can be targeted as part of intervention strategies to promote antimicrobial stewardship by animal health professionals in Nigeria, including the need for increased use of AST as a tool for supporting disease management, increased awareness of appropriate antibiotic use and greater dissemination of antibiotic use guidelines and enforcement of relevant regulation by government authorities.

1482. Local validation of the drug resistance in pneumonia clinical prediction score at a large academic medical center and a community hospital

BackgroundCommunity-acquired pneumonia (CAP) is responsible for ~1 million emergency department (ED) visits yearly and the leading cause of infection-related deaths. Given that increasing antibiotic resistance rates complicate appropriate empiric antibiotic selection, clinicians may benefit from tools to help identify patients at risk for drug-resistant pathogens (DRPs). Limitations of traditional tools, such as healthcare-associated pneumonia criteria (HCAP), have led to development of novel scoring tools such as the drug resistance in pneumonia (DRIP) score. Webb et al. showed the DRIP score was more predictive of CAP caused by DRPs than HCAP criteria. The objective of this study was to validate the DRIP score in a local population of hospitalized patients at an academic and a community medical center.MethodsPatients who presented to the ED between May 2017 and May 2019 were included in this retrospective review. Patients were included if they were ≥ 18 years diagnosed with CAP by radiographic evidence with respiratory culture positivity and susceptibility results. Exclusion criteria were: presence of non-bacterial non-respiratory pathogens, patients with cystic fibrosis, lung transplant or systemic co-infections. The primary outcome was validation of the DRIP score by comparing the sensitivity, specificity, negative and positive predictive values (NPV/PPV) to the derivation and validation study by Webb et al. Secondary outcomes were the percentage of CAP cases with DRPs and the predictability of DRP using the DRIP score versus HCAP criteria.ResultsA total of 164 patients were included; 60.4% were male with a median age of 70 years. The primary outcome shown in Table 1 demonstrated similar sensitivity, specificity, NPV, and PPV of the DRIP score to those in the study by Webb et al. Staphylococcus aureus (32.9%) and Streptococcus pneumoniae (27.4%) were the most commonly isolated pathogens and CAP due to DRPs occurred in 30.5% of patients. The DRIP score also demonstrated improved performance in predicting DRPs in CAP compared to the HCAP Criteria as shown in Table 2.Table 1. DRIP Score Validation Table 2. Predictability of the DRIP score vs. HCAP criteria ConclusionOur results further validate the DRIP score derived by Webb et al. in predicting DRPs in CAP. These results encourage a local prospective evaluation of the DRIP score as an antimicrobial stewardship tool.Disclosures All Authors: No reported disclosures

Modern views on the problem of sepsis

BACKGROUND. By defining the cornerstone of sepsis as the “systemic” of the inflammatory response in the form of cytokine violations, the authors of the corresponding concept are forced to recognize the etiological factors almost all pathogens of infectious diseases, which naturally go with the increased activity of cytokines in serum. Without diminishing the importance of these components of inflammation, one should pay attention to the postulate that not only viruses and protozoa never cause sepsis, but also all non-bacterial pathogens are not etiological factors of this disease, although they lead to severe systemic reactions accompanied by an increase in the level of proinflammatory cytokines. OBJECTIVE. The purpose of the work is to draw the attention of physicians to the discrepancy between the new notions about sepsis imposed on the medical community and accepted not only by anesthetists, resuscitative surgeons and surgeons, but also by many infectionists. MATERIALS AND METHODS. A detailed analysis of the clinical case of sepsis in a young woman is presented, which, due to adequate surgical and long-term conservative therapy, has safely recovered. CONCLUSIONS. Sepsis is a generalized acyclic infectious disease of the bacterial and/or fungal etiology that develops in an immunodeficient organism with characteristic pathomorphological and pathologist changes in organs and tissues.