Invasive Bloodstream Infections Research Articles

Antibiogram and Salmonella typhi detection in suspected patients using advanced PCR technique, serology, and conventional blood culture

Background & Objectives: Salmonella enterica serovar Typhi is a diverse gram-negative bacillus that causes life-threatening invasive bloodstream infection and remains a public health burden in developing countries. The antimicrobial resistance in Salmonella typhi has led to widespread multidrug resistance strains making complication in the treatment and demanding alternative therapies. Various diagnostics test such as blood culture, serological assay, and molecular assay are available. PCR is a newer gold standard method, but blood culture is still considered a definitive diagnosis of typhoid fever. Materials and Methods: A cross-sectional study was conducted. Venous blood was collected, and a widal test was performed to detect antibodies against O and H antigens in serum. Blood culture, isolation, and identification were performed using the standard techniques. The antibiogram of isolates was performed by the Kirby Bauer method. Amplification of the hilA gene through PCR was used for the molecular diagnosis. Results: Out of 141 suspected typhoid patients, 78 were males, and 63 were females. PCR detected maximum positivity rate (70%) followed by Widal test (43.26%) and blood culture (16.25%). PCR positive cases were highly prevalent in the male in less than 15 years of age group (14.8%), followed by 15-30 (12.7%) and 30-45 (9.1%). The isolated organism was found to be 100% sensitive to most antibiotics studied, except ofloxacin, which showed 71.4% sensitivity. In contrast, all the isolates were 100% resistant to nalidixic acid. None of the isolates showed multi-drug resistance. Conclusion: PCR is a sensitive, rapid, and better alternative than conventional methods that can be used in clinical diagnosis for early detection of the Salmonella typhi.

Preclinical validation of an Escherichia coli O-antigen glycoconjugate for the prevention of serotype O1 invasive disease.

The Escherichia coli serotype O1 O-antigen serogroup is a common cause of invasive bloodstream infections (BSI) in populations at risk such as newborns and the elderly. Sequencing of US BSI isolates and structural analysis of O polysaccharide antigens purified from strains that are representative of genotypic sub-groups confirmed the relevance of the O1a subtype as a vaccine antigen. O polysaccharide was purified from a strain engineered to produce long-chain O1a O-antigen and was chemically conjugated to CRM197 carrier protein. The resulting glycoconjugate elicited functional antibodies and was protective in mice against lethal challenges with virulent K1-encapsulated O1a isolates.

Epidemiology, Clinical, and Microbiological Characteristics of Multidrug-Resistant Gram-Negative Bacteremia in Qatar.

Antimicrobial resistance is a global healthcare threat with significant clinical and economic consequences peaking at secondary and tertiary care hospitals where multidrug-resistant Gram-negative bacteria (MDR GNB) lead to poor outcomes. A prospective study was conducted between January and December 2019 for all invasive bloodstream infections (BSIs) secondary to MDR GNB in Qatar identified during routine microbiological service to examine their clinical, microbiological, and genomic characteristics. Out of 3238 episodes of GNB BSIs, the prevalence of MDR GNB was 13% (429/3238). The predominant MDR pathogens were Escherichia coli (62.7%), Klebsiella pneumoniae (20.4%), Salmonella species (6.6%), and Pseudomonas aeruginosa (5.3%), while out of 245 clinically evaluated patients, the majority were adult males, with the elderly constituting almost one-third of the cohort and with highest observed risk for prolonged hospital stays. The risk factors identified included multiple comorbidities, recent healthcare contact, previous antimicrobial therapy, and admission to critical care. The in-hospital mortality rate was recorded at 25.7%, associated with multiple comorbidities, admission to critical care, and the acquisition of MDR Pseudomonas aeruginosa. Resistant pathogens demonstrated high levels of antimicrobial resistance but noticeable susceptibility to amikacin and carbapenems. Genomic analysis revealed that Escherichia coli ST131 and Salmonella enterica ST1 were the predominant clones not observed with other pathogens.

Targeting host deoxycytidine kinase mitigates Staphylococcus aureus abscess formation.

Host-directed therapy (HDT) is an emerging approach to overcome antimicrobial resistance in pathogenic microorganisms. Specifically, HDT targets host-encoded factors required for pathogen replication and survival without interfering with microbial growth or metabolism, thereby eliminating the risk of resistance development. By applying HDT and a drug repurposing approach, we demonstrate that (R)-DI-87, a clinical-stage anticancer drug and potent inhibitor of mammalian deoxycytidine kinase (dCK), mitigates Staphylococcus aureus abscess formation in organ tissues upon invasive bloodstream infection. Mechanistically, (R)-DI-87 shields phagocytes from staphylococcal death-effector deoxyribonucleosides that target dCK and the mammalian purine salvage pathway-apoptosis axis. In this manner, (R)-DI-87-mediated protection of immune cells amplifies macrophage infiltration into deep-seated abscesses, a phenomenon coupled with enhanced pathogen control, ameliorated immunopathology, and reduced disease severity. Thus, pharmaceutical blockade of dCK represents an advanced anti-infective intervention strategy against which staphylococci cannot develop resistance and may help to fight fatal infectious diseases in hospitalized patients.

Targeting host deoxycytidine kinase mitigates Staphylococcus aureus abscess formation

Host-directed therapy (HDT) is an emerging approach to overcome antimicrobial resistance in pathogenic microorganisms. Specifically, HDT targets host-encoded factors required for pathogen replication and survival without interfering with microbial growth or metabolism, thereby eliminating the risk of resistance development. By applying HDT and a drug repurposing approach, we demonstrate that (R)-DI-87, a clinical-stage anticancer drug and potent inhibitor of mammalian deoxycytidine kinase (dCK), mitigates Staphylococcus aureus abscess formation in organ tissues upon invasive bloodstream infection. Mechanistically, (R)-DI-87 shields phagocytes from staphylococcal death-effector deoxyribonucleosides that target dCK and the mammalian purine salvage pathway-apoptosis axis. In this manner, (R)-DI-87-mediated protection of immune cells amplifies macrophage infiltration into deep-seated abscesses, a phenomenon coupled with enhanced pathogen control, ameliorated immunopathology, and reduced disease severity. Thus, pharmaceutical blockade of dCK represents an advanced anti-infective intervention strategy against which staphylococci cannot develop resistance and may help to fight fatal infectious diseases in hospitalized patients.

Evolution of Invasive and Colonizing Pediatric Staphylococcus aureus Isolates

Abstract Background Staphylococcus aureus is the most common bacterial pathogen isolated in children with invasive bloodstream and musculoskeletal infections. A major barrier to vaccine and novel therapeutic development against S. aureus is its continuous evolution. Many recent and current vaccine candidates target antigens that may have appeared crucial to its pathogenesis, only to see these factors recede from circulating invasive strains. Characterization of clinically relevant S. aureus isolates over time is necessary to find targets for novel therapeutics. Efforts toward new interventions should target factors that remain prevalent in invasive isolates over time. Methods We obtained 131 invasive S. aureus isolates from children admitted to the Monroe Carell Jr. Children's Hospital at Vanderbilt from 2010 to 2022, and 246 colonizing isolates. Whole genome sequences were obtained using the Illumina sequencing platform. Virulence factors and multi-locus sequence type (MLST) were determined using Geneious software and through PubMLST, an open-access curated database. Results There were 10 unique clonal complexes (CC) identified among 320 isolates. CC8 remains the most common invasive clonal complex, though CC8 is significantly less frequent now than in 2010-2012. Diversity of invasive strains has increased substantially, with the emergence of CC5 and CC121 lineages causing invasive disease in children. CC1 was found exclusively in colonization isolates. Virulence factor prevalence has changed significantly over time. Panton-Valentine leucocidin (PVL), enterotoxins K and Q (SEK/SEQ), and the pathogenic arginine catabolic mobile element (ACME), have decreased significantly in invasive S. aureus isolates since 2010, from 53-70% to 21-35% of current isolates. Leukocidin ED (LukED) and surface protein staphylokinase (Sak) are strongly associated with invasive isolates compared to colonization isolates. Conversely, toxic shock toxin (TST) and Staphylococcal enterotoxin B (SEB) were seen more commonly in colonization isolates (12-15%) compared to invasive isolates (5-7%). The genes encoding for gamma hemolysins (HlgA-C), leukocidin AB (LukAB), iron-regulated surface proteins (IsdA, IsdB), staphylococcal binding immunoglobulin protein (sbi), extracellular fibrinogen-binding protein (Efb), and clumping factors A and B (ClfA, ClfB) were identified in all isolates tested. Figure 1 Figure 2 Conclusions Significant shifts have occurred over the past decade in the predominant circulating S. aureus strains and their virulence factor repertoires. The once-dominant CC8 (USA300 clone) has receded, and with that has come a significant reduction in some factors once thought crucial for pathogenesis. These findings also have implications for infection prevention and control practices, as eradication of colonizing strains with low potential for pathogenicity may inadvertently allow for replacement by more virulent strains.

Novel SCCmec variants in clonal complex 398 and lineage-specific pseudo-SCCmec identified in ST88 MRSA from invasive bloodstream infections in China.

Methicillin resistance in Staphylococcus aureus is primarily due to the mecA gene found in highly diverse staphylococcal cassette chromosome mec (SCCmec) elements, with an increasing number of variants being continually discovered. To characterize two novel SCCmec variants identified in clonal complex (CC) 398 strains and lineage-specific pseudo-SCCmec elements in the ST88 clone. WGS and comparative genomic analysis were used to elucidate the SCCmec element diversity of representative isolates. The non-typeable 47 kb SCCmec found in the CC398 strain SKLX55795 represents a novel subtype of XIV, showing significant differences in structural organization and genetic content within the joining regions compared with the XIV element from the prototype strain SC792. This unique subtype comprised remnants from various mobile genetic elements that encode antimicrobial resistance genes, ultimately forming a large MDR region. Genome analysis of CC398 strain SKLX61416 revealed the presence of a novel 50 kb composite SCCmec with two distinct domains, carrying the ccr gene complexes 5/8 and containing genes for the detoxification of arsenic and sulphide. Further sequence analysis disclosed that 44.23% (23/52) of ST88 strains in our collection carried a lineage-specific pseudo-SCCmec, termed ΨSCCmecST88. This ΨSCCmecST88 harboured the mec gene complex C2, along with a series of genes associated with heavy metal resistance, but lacked an approximately 28 kb region encompassing the ccr gene complex. Our findings provide evidence for the ongoing evolution of SCCmec elements within the CC398 and ST88 clones, underscoring the need for further surveillance to understand the biological significance of these elements.

Vaccine safety surveillance in Kenya using GAIA standards: A feasibility assessment of existing national and subnational research and program systems

BackgroundActive surveillance systems for monitoring vaccine safety among pregnant women address some of the limitations of a current passive surveillance approach utilized in low- and middle-income countries (LMIC). However, few active surveillance systems in LMIC exist.Our study assessed the feasibility of utilizing three existing data collection systems in Kenya for active surveillance of maternal immunization and to assess the applicability of Global Alignment of Immunization Safety Assessment in pregnancy (GAIA) case definitions that were initially developed for clinical trials within these systems. MethodsWe assessed applicability of GAIA case definition for maternal Tetanus Toxoid exposure, stillbirth, low birth weight, small for gestational age, Neonatal Invasive Blood Stream Infection (NIBSI), prematurity and neonatal death in two routine web-based health information systems (Kenya EMR and DHIS-2), and a web-based population-based pregnancy research platform (ANCOV11Antenatal, Intrapartum and Postnatal care COVID-19 Surveillance Study (ANCOV).) in Kenya. ResultsAll three HIS were capable of reporting selected outcomes to varying degrees of GAIA certainty. The ANCOV platform was the most robust in collecting and collating clinical data for effective maternal pharmacovigilance. The utilization of facility- and district-aggregated data limits the usefulness of DHIS-2 in pharmacovigilance as currently operationalized. While the Kenya EMR contained individual level data and meets the key considerations for effective pharmacovigilance, it was used primarily for HIV care and treatment records in a small proportion of health facilities and would require additional resources to expand to all antenatal care facilities and to link maternal and infant records. DiscussionPopulation-based research studies may offer a responsive short-term option for implementing maternal vaccine pharmacovigilance in LMICs. However, the foundation exists for long-term capacity building within the national health electronic data systems to provide this critical service as well as ensure participation of the country in international studies on maternal vaccine safety.

Multidrug-Resistant Shigella sonnei Bacteremia among Persons Experiencing Homelessness, Vancouver, British Columbia, Canada.

Increased invasive bloodstream infections caused by multidrug resistant Shigella sonnei were noted in Vancouver, British Columbia, Canada, during 2021-2023. Whole-genome sequencing revealed clonal transmission of genotype 3.6.1.1.2 (CipR.MSM5) among persons experiencing homelessness. Improvements in identifying Shigella species, expanding treatment options for multidrug resistant infections, and developing public health partnerships are needed.

P200 Lodderomyces elongisporus fungemia in a late post-operative patient with ventricular septal defect: case report

Poster session 2, September 22, 2022, 12:30 PM - 1:30 PMObjectivesTo report a case of Lodderomyces elongisporus fungemia in a late post-operative patient with the ventricular septal defect.MethodsInformed consent was obtained from the parents of the child. Clinical history was collected. Routine biochemical tests were conducted. Blood samples were sent to the bacteriology and mycology laboratory for culture. Radiological examination of the head was done to ascertain the cause of neurological manifestations.ResultsAn 11-year-old boy, previously diagnosed as a case of ventricular septal defect (VSD) and severe aortic regurgitation, had undergone VSD closure in December 2010 and aortic valve replacement in January 2011. He was discharged on oral anticoagulants. However, he did not follow up.In August 2018, he presented with fever and right-sided hemiparesis. Hemogram was within normal limits except for decreased hemoglobin. Bacteriological blood culture was sterile, but I.V. antibiotics were administered empirically. However, the patient started to have epileptic attacks and therefore was intubated and antiepileptics were administered. An NCCT of the head revealed a large intraparenchymal bleed. Echocardiography revealed intra-cardiac vegetation measuring 8 × 7 mm and moderate aortic regurgitation.Fungal blood culture inoculated in BACTEC Mycosis IC/F bottle flagged positive after 5 days of incubation. A smear and Gram stain from the same revealed budding yeast cells. Sub-culture was done on Sabouraud dextrose agar and HiCromeTM Candida Differential Agar, and blue-tinged colonies were observed on the latter. The isolate was identified as L. elongisporus when subjected to MALDI-TOF analysis. Identification was confirmed by sequencing the internal transcribed spacer (ITS) region of the ribosomal DNA.Antifungal susceptibility test was performed by broth microdilution as per CLSI guidelines. Antifungal therapy was initiated with liposomal amphotericin B, but he continued to have fever even after 1 week and consequently developed status epilepticus. CT scan of the brain revealed massive intracranial hemorrhage. Parents were advised neurosurgery, but they requested discharge against medical advice. The patient was lost to follow-up.Conclusions Lodderomyces elongisporus is a rare cause of invasive bloodstream infections and should not be ignored as a contaminant when isolated from sterile sites. It is often misidentified as Candida parapsilosis by conventional methods and commercially available systems but can be distinguished from it using chromogenic culture media and MALDI-TOF-MS. The current case report highlights the significance of L. elongisporus as a rare cause of invasive fungal infections, the difficulties faced in the identification of this pathogen, and the importance of newer diagnostic methods in identifying it.

Genetic and Structural Variation in the O-Antigen of Salmonella enterica Serovar Typhimurium Isolates Causing Bloodstream Infections in the Democratic Republic of the Congo.

ABSTRACTSalmonella enterica serovar Typhimurium causes a devastating burden of invasive disease in sub-Saharan Africa with high levels of antimicrobial resistance. No licensed vaccine is available, but O-antigen-based candidates are in development, as the O-antigen moiety of lipopolysaccharides is the principal target of protective immunity. The vaccines under development are designed based on isolates with O-antigen O-acetylated at position C-2 of abequose, giving the O:5 antigen. Serotyping data on recent Salmonella Typhimurium clinical isolates from the Democratic Republic of the Congo (DRC), however, indicate increasing levels of isolates without O:5. The importance and distribution of this loss of O:5 antigen in the population as well as the genetic mechanism responsible for the loss and chemical characteristics of the O-antigen are poorly understood. In this study, we Illumina whole-genome sequenced 354 Salmonella Typhimurium isolates from the DRC, which were isolated between 2002 and 2017. We used genomics and phylogenetics combined with chemical approaches (1H nuclear magnetic resonance [NMR], high-performance anion-exchange chromatography with pulsed amperometric detection [HPAEC-PAD], high-performance liquid chromatography–PAD [HPLC-PAD], and HPLC-size exclusion chromatography [HPLC-SEC]) to characterize the O-antigen features within the bacterial population. We observed convergent evolution toward the loss of the O:5 epitope predominantly caused by recombination events in a single gene, the O-acetyltransferase gene oafA. In addition, we observe further O-antigen variations, including O-acetylation of the rhamnose residue, different levels of glucosylation, and the absence of O-antigen repeating units. Large recombination events underlying O-antigen variation were resolved using long-read MinION sequencing. Our study suggests evolutionary pressure toward O-antigen variants in a region where invasive disease by Salmonella Typhimurium is highly endemic. This needs to be taken into account when developing O-antigen-based vaccines, as it might impact the breadth of coverage in such regions.

Mobility of antimicrobial resistance across serovars and disease presentations in non-typhoidal Salmonella from animals and humans in Vietnam.

Non-typhoidal Salmonella (NTS) is a major cause of bacterial enterocolitis globally but also causes invasive bloodstream infections. Antimicrobial resistance (AMR) hampers the treatment of these infections and understanding how AMR spreads between NTS may help in developing effective strategies. We investigated NTS isolates associated with invasive disease, diarrhoeal disease and asymptomatic carriage in animals and humans from Vietnam. Isolates included multiple serovars and both common and rare phenotypic AMR profiles; long- and short-read sequencing was used to investigate the genetic mechanisms and genomic backgrounds associated with phenotypic AMR profiles. We demonstrate concordance between most AMR genotypes and phenotypes but identified large genotypic diversity in clinically relevant phenotypes and the high mobility potential of AMR genes (ARGs) in this setting. We found that 84 % of ARGs identified were located on plasmids, most commonly those containing IncHI1A_1 and IncHI1B(R27)_1_R27 replicons (33%), and those containing IncHI2_1 and IncHI2A_1 replicons (31%). The vast majority (95%) of ARGS were found within 10 kbp of IS6/IS26 elements, which provide plasmids with a mechanism to exchange ARGs between plasmids and other parts of the genome. Whole genome sequencing with targeted long-read sequencing applied in a One Health context identified a comparatively limited number of insertion sequences and plasmid replicons associated with AMR. Therefore, in the context of NTS from Vietnam and likely for other settings as well, the mechanisms by which ARGs move contribute to a more successful AMR profile than the specific ARGs, facilitating the adaptation of bacteria to different environments or selection pressures.

The Role of the Oral Immune System in Oropharyngeal Candidiasis-Facilitated Invasion and Dissemination of Staphylococcus aureus.

Candida albicans and Staphylococcus aureus account for most invasive fungal and bacterial bloodstream infections (BSIs), respectively. However, the initial point of invasion responsible for S. aureus BSIs is often unclear. Recently, C. albicans has been proposed to mediate S. aureus invasion of immunocompromised hosts during co-colonization of oral mucosal surfaces. The status of the oral immune system crucially contributes to this process in two distinct ways: firstly, by allowing invasive C. albicans growth during dysfunction of extra-epithelial immunity, and secondly following invasion by some remaining function of intra-epithelial immunity. Immunocompromised individuals at risk of developing invasive oral C. albicans infections could, therefore, also be at risk of contracting concordant S. aureus BSIs. Considering the crucial contribution of both oral immune function and dysfunction, the aim of this review is to provide an overview of relevant aspects of intra and extra-epithelial oral immunity and discuss predominant immune deficiencies expected to facilitate C. albicans induced S. aureus BSIs.

Machine-learning based prediction of prognostic risk factors in patients with invasive candidiasis infection and bacterial bloodstream infection: a singled centered retrospective study

BackgroundInvasive candidal infection combined with bacterial bloodstream infection is one of the common nosocomial infections that is also the main cause of morbidity and mortality. The incidence of invasive Candidal infection with bacterial bloodstream infection is increasing year by year worldwide, but data on China is still limited.MethodsWe included 246 hospitalised patients who had invasive candidal infection combined with a bacterial bloodstream infection from January 2013 to January 2018; we collected and analysed the relevant epidemiological information and used machine learning methods to find prognostic factors related to death (training set and test set were randomly allocated at a ratio of 7:3).ResultsOf the 246 patients with invasive candidal infection complicated with a bacterial bloodstream infection, the median age was 63 years (53.25–74), of which 159 (64.6%) were male, 109 (44.3%) were elderly patients (> 65 years), 238 (96.7%) were hospitalised for more than 10 days, 168 (68.3%) were admitted to ICU during hospitalisation, and most patients had records of multiple admissions within 2 years (167/246, 67.9%). The most common blood index was hypoproteinemia (169/246, 68.7%), and the most common inducement was urinary catheter use (210/246, 85.4%). Moreover, the most frequently infected fungi and bacteria were Candida parapsilosis and Acinetobacter baumannii, respectively. The main predictors of death prognosis by machine learning method are serum creatinine level, age, length of stay, stay in ICU during hospitalisation, serum albumin level, C-Reactive protein (CRP), leukocyte count, neutrophil count, Procalcitonin (PCT), and total bilirubin level.ConclusionOur results showed that the most common candida and bacteria infections were caused by Candida parapsilosis and Acinetobacter baumannii, respectively. The main predictors of death prognosis are serum creatinine level, age, length of stay, stay in ICU during hospitalisation, serum albumin level, CRP, leukocyte count, neutrophil count, PCT and total bilirubin level.

TRIAZOLE RESISTANCE IN ASPERGILLUS FUMIGATUS-A COMPREHENSIVE REVIEW

Aspergillus fumigatus is a common ubiquitous fungal pathogen present in the environment including soil, decaying leaves, compost, grain crops and household dust. It can turn opportunistic in immunocompromised individuals causing allergic diseases, respiratory problems and invasive blood stream infections. Being saprophytic, it propagates by producing minute grey-green conidia that can become airborne and reach humans. In majority of cases, aspergillosis due to this organism can heal with treatment by antifungals. The azole compounds, one of the most important antifungal drugs, generally target the 14-α sterol demethylase enzyme, encoded by the cyp51A gene of the fungus, causing impaired membrane ergosterol synthesis. However in recent years the situation has turned grave due to development of azole resistant fungal species both in the environment as well as in the clinics. The main mechanism of resistance in A. fumigatus involves incorporation of tandem repeats in the promoter region of cyp51A, along with point mutations in the gene sequence. Resistant isolates tend to arise either due to excessive use of azole fungicides in the agricultural fields, from where they reach human through sporulation; or by prolonged treatment of patients with azole drugs. The early diagnosis of aspergillosis is very crucial for successful treatment of a patient. The article brings forth a comprehensive study of this organism, the mechanism of development and spread of azole resistant fungal isolates, genetic basis of development of azole resistance, detection of resistant strains and finally drugs used to combat the fungal infection.

Genomic epidemiology and characterisation of penicillin-sensitive Staphylococcus aureus isolates from invasive bloodstream infections in China: an increasing prevalence and higher diversity in genetic typing be revealed

ABSTRACT Many countries have reported increasing rates of penicillin-susceptible methicillin-sensitive Staphylococcus aureus (MSSA-PENS). To date, there is relatively little known about the current situation and molecular characteristics of MSSA-PENS in China. In this study, we carried out a laboratory-based multi-region retrospective study to investigate the genomic epidemiology and characterisation of MSSA-PENS isolated from invasive bloodstream infections (BSIs) across 17 provinces. The prevalence of MSSA-PENS isolates increased significantly over the 6-year period, with the proportion increasing from 3.51% in 2014–8.80% in 2019, an average relative increase of 22.14% per year (95% confidence interval 9.67%-34.61%, P for trend <0.001), suggesting that China is experiencing a resurgence of MSSA-PENS. Phylogenetic analysis showed a higher strain diversity occurred; the most frequent clonal complexes (CCs) identified were CC188 (17.14%), CC398 (15.71%) and CC5 (15.71%). Over half of MSSA-PENS strains were pan-susceptible, with erythromycin the most frequent resistance observed. Moreover, 25 isolates were identified as immune evasion cluster negative, including CC15, CC188 and CC1, and 6 strains encoded the Panton-Valentine leucocidin gene. Importantly, virulence assays showed that MSSA-PENS exhibited a level of virulence comparable to that of penicillin-resistant MSSA (MSSA-PENR), indicating that more-sensitive strains should not be mistaken for lacking aggressiveness in vivo. Furthermore, 11 of these isolates were confirmed as blaZ positive but phenotype sensitive, with different amino acid changes in blaZ. Our data support the recommendation to clinicians regarding the usage of penicillin in invasive BSIs caused by MSSA-PENS, which might create a novel opportunity for better antimicrobial stewardship in the future.

Epidemiology, Microbiological Characteristics and Clinical Outcomes of Invasive Blood Stream Infections of Group B Streptococcal Isolates From Qatar

Background: Group B Streptococci (GBS) or Streptococcus agalactiae colonize humans genitourinary and gastrointestinal tracts particularly in females1. The pathogen is capable of causing invasive disease primarily in infants, pregnant and postpartum women as well as the elderly and patients with comorbidities2. There is a paucity of studies on the disease with regional differences in prevalence and presentation of invasive bloodstream infection (BSI)3. In this study, we aim to assess the prevalence, microbiological characteristics as well as clinical outcomes of invasive GBS disease from all ages groups at Hamad Medical Corporation (HMC), Qatar. Methods: A retrospective study was conducted on all patients with microbiologically confirmed GBS bacteremia between January 2015–March 2019. Demographic, microbiological characteristics, as well as clinical data, were extracted from the hospital information system. Results: Out of the 196 confirmed cases of GBS bloodstream infections, 63.7 % were females (125/196) of whom 44.8 % were pregnant (56/125). There were three distinct age group populations: pediatric less than 4 years of age at 35.7 %, young adults 25-34 (20.9 %), and the elderly &gt; 65 years (17.4 %). Presenting symptoms were fever in 53 % of the cases (104/196) (Table 1). Microbiological characteristics using disc diffusion tests demonstrated all isolates were universally sensitive to penicillin (100%, 196/196) with significant resistance to clindamycin at 28.6 % (56/196) and erythromycin at 49 % (96/196) of which 34.4 % (33/96) had inducible clindamycin resistance (Figure 1). The clinical outcomes showed a high cure rate of 87.25% (171/196) with low complications at 8.76 % (17/196) and 4% (8/196) 30-day mortality. Conclusion: Streptococcus agalactiae bloodstream infection in Qatar is common in females, affects the very young, and the elderly. The organism remains universality sensitive to penicillin with significant resistance to clindamycin and erythromycin. Patients present with mild symptoms have high cure rates, low complications, and safe outcomes for the majority of cases.

192. Epidemiology, Microbiological Characteristics and Clinical Outcomes of Invasive Blood Stream Infections of Group B Streptococcal Isolates From Qatar

BackgroundGroup B Streptococci (GBS) or Streptococcus agalactiae colonize humans genitourinary and gastrointestinal tracts particularly of females. The pathogen is capable of causing invasive disease primarily in infants, pregnant and postpartum women as well as the elderly and patients with comorbidities. There is paucity of studies of the disease with regional differences in prevalence and presentation of invasive blood stream infection (BSI). In this study, we aim to assess prevalence, microbiological characteristics as well as clinical outcomes of invasive GBS disease from all ages groups at Hamad Medical Corporation (HMC), Qatar.MethodsA retrospective study was conducted on all patients with microbiologically confirmed GBS bacteraemia between January 2015–March 2019. Demographic, microbiological characteristics as well as clinical data were extracted from hospital information system.ResultsOut of 196 confirmed cases of GBS blood stream infection, 63.7 % were females (125/196) of whom 44.8 % were pregnant (56/125), 53.6 % (30/56) were colonized while 36.3 % (71/196) were males. There were three distinct age group populations, paediatric less than 4 years of age at 35.7 %, young adults 25-34 (20.9 %) and the elderly > 65 year (17.4 %). Presenting symptoms were mild with fever recognised in only 53 % of cases (104/196) while 89% of cases had low Pitt bactermia score of 0-2. Microbiological characteristic using disc diffusion tests demonstrated all isolates were universally sensitive to penicillin (100%, 196/196) with significant resistance to clindamycin at 28.6 % (56/196) and erythromycin at 49 % (96/196) of which 34.4 % (33/96) had inducible clindamycin resistance. Clinical outcome showed high cure rate of 87.25% (171/196) with low complications at 8.76 % (17/196) and 4% (8/196) 30-day mortality. Antibiotic sensitivity profile for GBS isolates Conclusion Streptococcus agalactiae blood stream infection in Qatar is common in females, affects the very young, young adults and the elderly. Almost half of affected pregnant women are colonized. The organism remains universality sensitive to pencilling with significant resistance to clindamycin and erythromycin. Patients presents with mild symptoms with high cure rates, low complications and safe outcome for the majority of cases. Disclosures All Authors: No reported disclosures

TRIAZOLE RESISTANCE IN ASPERGILLUS FUMIGATUS-A COMPREHENSIVE REVIEW

Aspergillus fumigatus is a common ubiquitous fungal pathogen present in the environment including soil, decaying leaves, compost, grain crops and household dust. It can turn opportunistic in immunocompromised individuals causing allergic diseases, respiratory problems and invasive blood stream infections. Being saprophytic, it propagates by producing minute grey-green conidia that can become airborne and reach humans. In majority of cases, aspergillosis due to this organism can heal with treatment by antifungals. The azole compounds, one of the most important antifungal drugs, generally target the 14-α sterol demethylase enzyme, encoded by the cyp51A gene of the fungus, causing impaired membrane ergosterol synthesis. However in recent years the situation has turned grave due to development of azole resistant fungal species both in the environment as well as in the clinics. The main mechanism of resistance in A. fumigatus involves incorporation of tandem repeats in the promoter region of cyp51A, along with point mutations in the gene sequence. Resistant isolates tend to arise either due to excessive use of azole fungicides in the agricultural fields, from where they reach human through sporulation; or by prolonged treatment of patients with azole drugs. The early diagnosis of aspergillosis is very crucial for successful treatment of a patient. The article brings forth a comprehensive study of this organism, the mechanism of development and spread of azole resistant fungal isolates, genetic basis of development of azole resistance, detection of resistant strains and finally drugs used to combat the fungal infection.

Pseudomonas aeruginosa Positivity and Sensitivity in Invasive Bloodstream Infections Using Automated Bactec in Tertiary Care Teaching Hospital of North India

Background: Pseudomonas aeruginosa is one of the most commonly encountered gram-negative aerobic bacilli in the differential diagnosis of several probable hospital-acquired infections. Hence, the present study is designed to determine the Pseudomonas positivity and sensitivity in Invasive bloodstream infections using automated Bactec systems as the Antibiotic Sensitivity Profiles differ from one clinical setting to another.&#x0D; Material and Methods: All the blood culture samples received in the Department of Microbiology for culture by Bactec Bd fx from July 2015 to June 2016 were included in the study. The blood culture was observed in the Bactec bd fx system for at least 5 days before they are reported as sterile.&#x0D; Results: Among the total 1275 cultures which were positive for bacteria, 931(73.02%) were positive for gram-negative bacteria. Among the total of 931culture which were positive for gram-negative bacteria, Pseudomonas aeruginosa was isolated in 120(12.89%) cultures. Maximum was found in the age group of 0-1 years 33(27.50%) followed by 19-45 years 26(21.67%). Pseudomonas spp isolates were 100.00% sensitive to Colistin followed by Levofloxacin 84.44%, Piperacillin Tazobactum 82.50%, PB 77.50%, Amikacin 75.00%, Cefepime 75.00% while Pseudomonas spp isolates were 90% resistant to Ampicillin followed by Ceftazidime clavulanic acid 82.64% and Aztreonam 70.31%.&#x0D; Conclusion: Pseudomonas aeruginosa is one of the most common organisms among Gram-Negative isolates and the most commonly isolated in the neonate and infant age group. All the Pseudomonas isolates showed maximum sensitivity to Colistin followed by Levofloxacin, Piperacillin Tazobactum, Amikacin while they were most resistant to Ampicillin followed by Ceftazidime clavulanic acid and Aztreonam. Some alternative novel techniques need to be developed to counter the increasing menace of antibiotic resistance in this particular pathogenic bacteria