Cause Of Bloodstream Infections Research Articles

Bloodstream infection and ventilator-associated pneumonia in patients with coronavirus disease 2019 (COVID-19) supported by extracorporeal membrane oxygenation.

Extracorporeal membrane oxygenation (ECMO) has been widely used in the care of patients with respiratory failure from coronavirus disease 2019 (COVID-19). We characterized bloodstream infections (BSIs) and ventilator-associated pneumonias (VAPs) in COVID-19 patients supported with ECMO, and we investigated their impact on patient outcomes. Retrospective cohort study from March 1, 2020, to June 30, 2021. Academic tertiary-care referral center. Consecutive adult patients admitted for COVID-19 who received ECMO. We identified BSIs and VAPs and described their epidemiology and microbiology. Cumulative antimicrobial use and the specific management of BSIs were determined. Multivariate time-dependent Cox proportional hazards models were constructed to evaluate the impact of BSIs and VAPs on mortality, controlling for age, receipt of COVID-19-specific therapeutics, and new renal replacement therapy. We identified 136 patients who received ECMO for COVID-19 pneumonia during the study period. BSIs and VAPs occurred in 81 patients (59.6%) and 93 patients (68.4%), respectively. The incidence of BSIs was 29.5 per 1,000 ECMO days and increased with duration of ECMO cannulation. Enterococci, Enterobacterales, and Staphylococcus aureus were the most common causes of BSIs, whereas S. aureus, Klebsiella species, and Pseudomonas aeruginosa comprised the majority of VAPs. Mean antibiotic use comprised 1,031 days of therapy per 1,000 ECMO days (SD, 496). We did not detect an association between BSIs or VAPs and mortality. BSIs and VAPs are common in COVID-19 ECMO-supported patients. Efforts to optimize their diagnosis, prevention, and management should be prioritized.

The Role of Metagenomics Next-Generation Sequencing (mNGS) in Early Diagnosis of Bloodstream Infection in Hematologic Patients with Febrile Neutropenia: A Multicenter Prospective Study

Background: Bloodstream infection (BSI) is a lethal complication in hematologic patients with febrile neutropenia (FN). The delayed diagnosis and intervention will lead to significant mortality. Unfortunately, the traditional golden standard diagnostic method using blood culture (BC) can only identify pathogens in 20-30% patients with BSI, and usually needs more than 48 hours. Therefore, novel methods with fast turnover, improved sensitivity and specificity are needed. Metagenomics next-generation sequencing (mNGS) shows promise as diagnostic testing for difficult and critical infectious diseases in immunodeficient hosts, but its significance in BSI of hematological patients remains unclear, and has not been evaluated in prospective study. Aims: To evaluate the ability of mNGS to identify infectious etiologies in FN patients with BSI. Method: This study was prospective performed in four Chinese hematologic centers since October 2021. For patients≥15 years with hematologic diseases, patients were screened at the onset of neutropenia. At the onset of FN, Peripheral blood specimens were collected per subject for simultaneous BC and mNGS (separate sequencing for plasma and blood cells). All patients will be followed for 14 days, or until death before 14 days. The intervention was per the attending physician. The primary endpoints of this study is the sensitivity and specificity of mNGS. Thepositive agreement was defined as mNGS identified at least one same pathogen as initial BC. The negative agreement was defined as both mNGS and BC were negative. And the adjudication of the result of BC, mNGS, and clinical diagnosis was evaluated by 4 independent specialists in hematology. Clinical adjudication categorized mNGS results as: Definite, mNGS identified at least one pathogen also found by BC or SMT with in 7 days; Probable, mNGS result was concordant with a clinical diagnosis of BSI in FN; Possible, mNGS result was consistent with BSI but not considered a common cause of FN; Unlikely, mNGS result was not a plausible cause of BSI in FN. This study was registered on ClinicalTrials.gov ID: NCT05149547. This is an interim analysis of 134 patients enrolled in this multicenter, prospective observational study. Results: Te basic information of the patients was summarized in table 1. Clinical adjudication categorized mNGS results as: Definite (N=24); Probable (N=21); Possible (N=7); Unlikely (N=49). Definite, probable and possible cases were regarded as true positives. The positive percent agreement (PPA) and negative percent agreement (NPA) with BC were 80.0% (20/25) and 25.7% (28/109) respectively; 44% of mNGS results were polymicrobial (except viruses). According to the clinical adjudication, mNGS sensitivity and specificity were 94.6% (52/55) and 38.0% (30/79) respectively (table 2 and table 3). Compared with BC, the reporting time of mNGS was significant shorter (24.8±4.0 vs. 72.3±21.2 h, p < 0.05). Conclusions: Compared with conventional BC, mNGS might provide an early and rapid microbiological diagnosis of BSI in hematologic patients with FN. However, the clinical application needs pending further study. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Clinical and genomic analysis of virulence-related genes in bloodstream infections caused by Acinetobacter baumannii

ABSTRACT Acinetobacter baumannii has emerged as a common cause of bloodstream infections, which is associated with high mortality and long periods of hospitalization. To advance the medical care of our patients, the study was designed to identify microbial characteristics associated with poor clinical outcomes. A collection of 32 A. baumannii bloodstream isolates with diverse genetic backgrounds (as determined by multilocus sequence typing) was studied. These isolates were recovered by unique patients (18 males, 14 females; age range: 17 days to 87 years) between 2011 and 2018. A sequential screening approach (cross-referencing analyses using different endpoints) was used to identify isolates with the best correlation between bacterial virulence and clinical prognosis. Isolates associated with more rapid in vitro growth rate, shorter median survival time in pre-clinical infection models, and hospital mortality were selected as candidates for high virulence, while those with opposite characteristics were selected as controls with low virulence. Whole genome sequencing was undertaken in the most promising clinical isolates. We found five virulence genes (beta-hemolysin/cytolysin, Cpi-1a + Cpi-1 (SPI-1 like), enhanced entry proteins, FbpABC, Paa) and 1 secretory system (T6SS) only present in a highly virulent isolate (AB23), compared to a low virulence control isolate (AB6). These genetic elements could be associated with the poor prognosis of A. baumannii bacteraemia and further investigations are warranted.

Prevalence and Impact of Co-infection in Critically Ill COVID-19 Patients

Objective: To determine the epidemiology and impact of co-infection on COVID-19 pneumonia in critical care setting. Methods: This was a single center- retrospective study of COVID-19 patients, who were admitted to intensive care unit between March 2020-April 2021. Only patients with microbiological evaluation of blood, respiratory, or urine culture data were included. Community onset bacterial co-infection (COI) was defined as infection diagnosed within 48 hours and hospital acquired bacterial infection (HAI) after 48 hours of hospital admission. Both COI and HAI were further categorized into respiratory, blood or urinary sources. Demographics, laboratory and hospitalization outcomes were compared between patients with and without COI and HAI. Results: Among the 141 patients, COI was found in 25/132 patients (19%) and HAI in 41/109 patients (38%). COI was associated with younger age, lower body mass index (BMI) and being from nursing or long- term care facility. HAI was associated with longer length of hospital stay (29 vs 15 days). Staphylococcus aureus pneumonia (31.3%) and Pseudomonas aeruginosa pneumonia (40.0%) were the most common cause of COI and HAI respectively. Overall, gram negative bacteria predominated in both community and hospital acquired pneumonia. Candida was the single most common cause of blood stream infection in HAI (23%). The hospital survival was not significantly different with or without COI. Conclusion: In the critical care setting, a significant proportion of patients with COVID-19 had COI and HAI, especially patients from nursing or long-term care facility. Antibiotic coverage for COI and HAI pneumonia should account for the increase in prevalence of Staphylococcus aureus and Pseudomonas aeruginosa respectively.

Determine the microbial profile of catheter related sepsis in ICU

Background: Intravenous catheter-related blood stream infections (PVC-BSIs) are one of the common causes of death and illness in hospitals worldwide. Failure to practice adequate aseptic techniques is a leading cause of blood stream infections caused by catheters. The aim of this study to identify the microbiological makeup of catheter-related sepsis in the intensive care unit. Materials and methods: Participants comprised all intensive care unit (ICU) inpatients who had a peripheral venous catheter (PVC) implanted and who showed symptoms of septicemia within 48 hours after PVC implantation. Kirby-Brauer disc diffusion technique was used to test the antibiotic susceptibility of the bacterial isolates, as recommended by the CLSI. Results: Twenty percent of patients had identical bacterial growth in PVC tip cultures and blood cultures, suggesting peripheral venous catheter-related bloodstream infection (PVC- BSI), while twenty-five percent of patients were colonised and thirty percent of patients had bloodstream infections unrelated to the catheter. For one-quarter of patients, (25%) no organism development was identified. Among the 20 patients diagnosed with PVC-BSI, 8 (40%) were found to have infections caused by Staphylococcus aureus, 4 (20%) by Klebsiella species, 4 (20%) by CONS, 2 (10%) by Enterococcus species, and 1 (5%) by both Acinetobacter and Pseudomonas species.

EPIDEMIOLOGY, PREDISPOSING FACTORS AND OUTCOME OF STAPHYLOCOCCUS AUREUS BACTEREMIA IN NEUTROPENIC PATIENTS

Staphylococcus aureus is a common cause of bloodstream infection in neutropenic patients. We analyzed trends in incidence, epidemiology, predisposing factors and outcome of S. aureus bacteremia (SAB) in febrile neutropenic patients. We reviewed a database of febrile neutropenia at a single institution in Brazil in a 30-year period (January 1991 to December 2020). We divided in 3 periods: 1991-1994 (period 1), 2001-2010 (period 2) and 2011-2020 (period 3), and looked at incidence rates, risk factors and mortality. Risk factors and prognostic factors were evaluated by univariate (Fisher or Chi-square for categorical variables and Wilcoxon test for continuous variables) and multivariate (logistic regression) analysis. We diagnosed 62 (3%) episodes of SAB in 2,243 episodes of febrile neutropenia, 23 (38%) of which were caused by methicillin-resistant S. aureus (MRSA). The incidence of SAB per 1,000 days of neutropenia was 1.57, 2.53 and 1.50 in periods 1, 2 and 3, respectively (p > 0.05), and of MRSA was 0.49, 0.84 and 1.07, respectively (p > 0.05). Most infections (70%) were diagnosed in the first day of fever and the clinical presentation were skin infection (19%), catheter-related infection (14%) and pneumonia (3%). Complications like endocarditis or osteomyelitis were not observed. The only factor associated with S. aureus bacteremia by multivariate analysis was cellulitis at site of catheter exit site or tunnel on day 1 of fever (odds ratio [OR] 4.34, 95% confidence interval [CI] 2.05 – 9.16), whereas quinolone prophylaxis was protective (OR 0.37, 95% CI 0.18 - 0.74). The crude mortality of SAB was 30.6%, compared 13.8% in patients without this infection (p < 0.001). However, early mortality (within 3 days of start of empiric antibiotic therapy) was not significantly different (4.8% vs. 1.9%, p = 0.08). The mortality with MRSA was higher than with methicillin-susceptible S. aureus (47.8% vs. 13.9%, p < 0.001), but no difference was found regarding early mortality (5.0 vs 1.7%, p = 0.27). Among various predictors of death during febrile neutropenia MRSA bacteremia (but not methicillin-sensitive) was associated with an increased risk of death by multivariate analysis. The median time from febrile neutropenia to death in MRSA episodes was 19 days. The incidence of SAB over the period remained stable. Complication of SAB were not common. Although the crude mortality was higher with SAB (including MRSA), it was not associated with early deaths, thus not demanding anti-staphylococcal coverage in the first day of febrile neutropenia. MRSA bacteremia was associated with increased risk of death, with most deaths occurring after 2 weeks of febrile neutropenia.

Assessment of the antifungal susceptibility profile and virulence factors of non-albicans candida species obtained from the infection of the bloodstream

Background: Earlier the fungal infection spectrum was considered to be only restricted to mucocutaneous and cutaneous tissues. However, this consideration has now changed. The threatening rise in the incidence of invasive mycosis is seen recently. Despite advancements in diagnostic and therapeutic modalities, high mortality rates are linked to invasive mycosis. The most common cause of bloodstream infections is Candida spp. Among candida genus, the most pathogenic species is C. Albicans, recent literature data has shown the emergence of treatment-resistant, relatively uncommon, and unusual nonalbicans Candida (NAC) spp. Aim: The present study was conducted to assess the antifungal susceptibility profile and virulence factors of non-Albicans candida species obtained from the infection of the bloodstream. Material and methods: The present study included blood culture isolates of nonalbicans Candida (NAC) spp. which were identified to species level using the standard mycological protocol. This NAC spp. were screened for virulence factors production including biofilm formation, hemolysin, and extracellular hydrolytic enzymes. Ezy MIC strip was used for assessing the antifungal susceptibility profile of these isolates. Results: 100% (n=1) C. rugosa NAC spp. showed hemolysin production. In C. gulliermondii, 50% (n=1) subject showed phospholipase production and biofilm formation each.

Diagnostic MALDI-TOF MS can differentiate between high and low toxic Staphylococcus aureus bacteraemia isolates as a predictor of patient outcome.

Staphylococcus aureus bacteraemia (SAB) is a major cause of blood-stream infection (BSI) in both healthcare and community settings. While the underlying comorbidities of a patient significantly contributes to their susceptibility to and outcome following SAB, recent studies show the importance of the level of cytolytic toxin production by the infecting bacterium. In this study we demonstrate that this cytotoxicity can be determined directly from the diagnostic MALDI-TOF mass spectrum generated in a routine diagnostic laboratory. With further development this information could be used to guide the management and improve the outcomes for SAB patients.

P239 Molecular identification and antifungal susceptibility pattern of Candida species isolated from pediatrics with high colonization index in the Children Medical Center, Tehran

Poster session 2, September 22, 2022, 12:30 PM - 1:30 PMObjectivesCandidemia is the third leading cause of bloodstream infections whereas it is the second leading cause of sepsis-related mortality in children and subsequently, understanding a link between such infection and Candida colonization is an important issue for clinicians for decades; so, this link has proposed the colonization index as the ‘missing link’. The aim of this study was to evaluate the Candida colonization index in pediatric patients staying at intensive care units (ICUs) as well as bone marrow transplantation (BMT) unit and to determine the species distribution and susceptibility pattern of the isolates against several antifungal drugs.Material and MethodsThis study was conducted in the Children's Medical Center in Tehran-Iran between March 2019 and September 2019. Totally, 661 samples from 83 patients including oral cavity, skin surrounded catheters; ear, throat, nasal, and urine cultures were collected. Candida colonization index (CI) was calculated according to the previous study's description. CHROMagar Candida medium was applied for primary/multiple species identification and the isolates were then identified by using PCR-based methods to the species-specific complex level. Antifungal Susceptibility test was performed according to the Clinical and Laboratory Standards protocol published as M27-A2 and M60 documents. Fluconazole (FLZ), itraconazole (ITZ), voriconazole (VRZ), ravuconazole (RVZ), and isavuconazole (ISZ), caspofungin (CAS) and anidulafungin (AFG), and amphotericin B were used.ResultsOf 661 samples, 178 samples from 50 individuals (27%) were considered as positive cultures, amongst CI >0.5 confirmed in 29 cases (58% of positive samples). Candida albicans was reported as the most frequent species in BMT and IICU. Notably, C. krusei was the most prevalent species in PICU and the second in IICU. Candida albicans (n = 53, 49.5%) followed by C. glabrata (n = 20, 18.7%), C. krusei (n = 15, 14%), C. parapsilosis (n = 12, 11.2%) were the most frequent Candida species in patients with CI >0.5. Among FLZ-resistant strains, 12 isolates (7.01%) were multi-azole resistant which showed high MICs against both ISZ and RVZ and 7 strains (4.09%) were resistant to all echinocandins. ISZ, RVZ, and AFG were reported as the most effective antifungals, regarding the values of GM.ConclusionIn the present study, more than half of children with positive yeast cultures had CI >0.5 representing the high possibility of developing invasive candidiasis. However, none of the children with CI ≥0.5 developed invasive candidiasis during the time of the study. To the best of our knowledge, there is no study about the evaluation of CI in pediatrics in Iran. More detailed and larger studies should be made to understand the impact of risk factors on CI value in the future.

P150 Profile of Candidemia in a national level HAI Surveillance Network of India

Poster session 2, September 22, 2022, 12:30 PM - 1:30 PMBackground Candida is responsible for roughly 96% of all opportunistic mycoses and is a major cause of bloodstream infections (BSIs). The potential for nosocomial spread of Candidemia infections is a new concern concurrent with the rapid expansion of intensive care facilities for COVID-19 patients. With the pandemic of COVID-19 now moving into 2022, it is understood that critically ill COVID-infected patients in the ICUs are commonly infected with highly resistant bacterial and fungal infections.ObjectiveTo estimate the incidence rates and compare the epidemiology of candidemia in COVID infected and non-infected patients requiring ICU care.MethodologyIn this 2-year retrospective multicentric study, we present the findings on candidemia from the Healthcare-Associated Infections (HAI) surveillance network which includes 40 hospitals across India and with special emphasis on differences in the epidemiology of Candidemia in COVID infected and non-infected patients in the pre-COVID (April 2019 to April 2020) and COVID times (April 2020 to April 2021) across this network. We compared the incidence of candidemia between COVID infected and non-infected patients using Poisson regression analysis. Chi-squared (χ2) test was used to test for differences in variables such as gender and 14-day mortality between the patients and Wilcoxon rank-sum (Mann-Whitney) test was used to compare median between the patients.ResultsA total of 628 patients with candidemia were screened from HAI Surveillance Database where 68 patients are COVID infected and 560 non-infected patients from both pre-COVID and COVID periods. Incidence of Candida-associated BSI increased significantly from 1.47 (95% CI, 1.35-1.60) to 3.08 (95% CI, 2.38-3.92) in non-infected and COVID-infected patients respectively, while in CLABSI the rates increased from 2.62 (95% CI, 2.34-2.92) in non-infected to 5.99 (95% CI, 4.30-8.12) in COVID-infected patients. COVID infected patients in the age group (>60 years) were significantly more prone to candidemia compared to non-infected patients. During the COVID period, the maximum time for candidemia to develop (from the time of ICU admission) in COVID-infected patients was shorter (<65 days) than in non-infected patients (>90 days).ConclusionWe observed an increased incidence of candidemia in hospitalized patients during the COVID period compared with the same during the pre-COVID period.

Pandemic clone USA300 in a Brazilian hospital: detection of an emergent lineage among methicillin-resistant Staphylococcus aureus isolates from bloodstream infections

BackgroundStaphylococcus aureus is one of the leading causes of bloodstream infections (BSI) worldwide. In Brazil, the hospital-acquired methicillin-resistant S. aureus USA100/SCCmecII lineage replaced the previously well-established clones. However, the emergence of community-associated (CA) MRSA lineages among hospitalized patients is an increasing issue.MethodsConsecutive S. aureus isolates recovered from BSI episodes of patients admitted between January 2016 and December 2018 in a Brazilian teaching hospital were tested for antimicrobial resistance, their genotypic features were characterized, and the clinical characteristics of the patients were evaluated.ResultsA total of 123 S. aureus isolates were recovered from 113 patients. All isolates were susceptible to linezolid, teicoplanin and vancomycin and 13.8% were not susceptible to daptomycin. Vancomycin MIC50 and MIC90 of 2 mg/L were found for both MRSA and MSSA isolates. The MRSA isolation rate was 30.1% (37/123), and 51.4% of them carried the SCCmec type II, followed by SCCmecIV (40.5%). Among the 37 MRSA isolates, the main lineages found were USA100/SCCmecII/ST5 and ST105 (53.7%) and USA800/ST5/SCCmecIV (18.9%). Surprisingly, six (16%) CA-MRSA isolates, belonging to USA300/ST8/SCCmecIVa that carried PVL genes and the ACME cassette type I, were detected. These six patients with USA300 BSI had severe comorbidities, including cancer, and most had a Charlson score ≥ 5; furthermore, they were in wards attended by the same health professionals. MRSA isolates were associated with hospital acquired infections (p = 0.02) in more elderly patients (p = 0.03) and those diagnosed with hematologic cancer (p = 0.04). Among patients diagnosed with MRSA BSI, 19 (54.3%) died.ConclusionsThe pandemic MRSA USA300 was detected for the first time in the Brazilian teaching hospital under study, and its cross-transmission most probably occurred between patients with BSI. This lineage may already be circulating among other Brazilian hospitals, which highlights the importance of carrying out surveillance programs to fight multidrug resistant and hypervirulent isolates.

Trends in Occurrence and Phenotypic Resistance of Coagulase-Negative Staphylococci (CoNS) Found in Human Blood in the Northern Netherlands between 2013 and 2019.

Background: For years, coagulase-negative staphylococci (CoNS) were not considered a cause of bloodstream infections (BSIs) and were often regarded as contamination. However, the association of CoNS with nosocomial infections is increasingly recognized. The identification of more than 40 different CoNS species has been driven by the introduction of matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. Yet, treatment guidelines consider CoNS as a whole group, despite increasing antibiotic resistance (ABR) in CoNS. This retrospective study provides an in-depth data analysis of CoNS isolates found in human blood culture isolates between 2013 and 2019 in the entire region of the Northern Netherlands. Methods: In total, 10,796 patients were included that were hospitalized in one of the 15 hospitals in the region, leading to 14,992 CoNS isolates for (ABR) data analysis. CoNS accounted for 27.6% of all available 71,632 blood culture isolates. EUCAST Expert rules were applied to correct for errors in antibiotic test results. Results: A total of 27 different CoNS species were found. Major differences were observed in occurrence and ABR profiles. The top five species covered 97.1% of all included isolates: S. epidermidis, S. hominis, S. capitis, S. haemolyticus, and S. warneri. Regarding ABR, methicillin resistance was most frequently detected in S. haemolyticus (72%), S. cohnii (65%), and S. epidermidis (62%). S. epidermidis and S. haemolyticus showed 50–80% resistance to teicoplanin and macrolides while resistance to these agents remained lower than 10% in most other CoNS species. Conclusion: These differences are often neglected in national guideline development, prompting a focus on ‘ABR-safe’ agents such as glycopeptides. In conclusion, this multi-year, full-region approach to extensively assess the trends in both the occurrence and phenotypic resistance of CoNS species could be used for evaluating treatment policies and understanding more about these important but still too often neglected pathogens.

Urban rats as carriers of invasive Salmonella Typhimurium sequence type 313, Kisangani, Democratic Republic of Congo.

Invasive non-typhoidal Salmonella (iNTS-mainly serotypes Enteritidis and Typhimurium) are major causes of bloodstream infections in children in sub-Saharan Africa, but their reservoir remains unknown. We assessed iNTS carriage in rats in an urban setting endemic for iNTS carriage and compared genetic profiles of iNTS from rats with those isolated from humans. From April 2016 to December 2018, rats were trapped in five marketplaces and a slaughterhouse in Kisangani, Democratic Republic of the Congo. After euthanasia, blood, liver, spleen, and rectal content were cultured for Salmonella. Genetic relatedness between iNTS from rats and humans-obtained from blood cultures at Kisangani University Hospital-was assessed with multilocus variable-number tandem repeat (VNTR) analysis (MLVA), multilocus sequence typing (MLST) and core-genome MLST (cgMLST). 1650 live-capture traps yielded 566 (34.3%) rats (95.6% Rattus norvegicus, 4.4% Rattus rattus); 46 (8.1%) of them carried Salmonella, of which 13 had more than one serotype. The most common serotypes were II.42:r:- (n = 18 rats), Kapemba (n = 12), Weltevreden and Typhimurium (n = 10, each), and Dublin (n = 8). Salmonella Typhimurium belonged to MLST ST19 (n = 7 rats) and the invasive ST313 (n = 3, isolated from deep organs but not from rectal content). Sixteen human S. Typhimurium isolates (all ST313) were available for comparison: MLVA and cgMLST revealed two distinct rat-human clusters involving both six human isolates, respectively, i.e. in total 12/16 human ST313 isolates. All ST313 Typhimurium isolates from rats and humans clustered with the ST313 Lineage 2 isolates and most were multidrug resistant; the remaining isolates from rats including S. Typhimurium ST19 were pan-susceptible. The present study provides evidence of urban rats as potential reservoirs of S. Typhimurium ST313 in an iNTS endemic area in sub-Saharan Africa.

P8.016: Gram Negative Blood Stream Infection in Renal Transplant Recipients: Risk Factors and Outcome From a Transplant Center in Pakistan

Background: Gram-negative bacteremia (GNB) is a common cause of bloodstream infection in renal transplant recipients (RTR). The risk factors are cytomegalovirus infection (CMV), pre-transplant dialysis, acute rejection, urological abnormalities, and ureteral stent. The mortality rate is 2.5 to 11%. Considering the huge impact on morbidity and mortality, our aim is to analyze the characteristics and outcomes of GNB in RTRs. Methods: A case-control study at Sindh Institute of Urology and Transplantation (SIUT), Karachi, Pakistan. The files of all renal transplant recipients who had documented GNB from January 2015 to December 2017 were reviewed till December 2020. The controls were matched with age, sex, and date of transplant. The first episode of GNB was taken. Clinical features, received anti-thymocyte globulin (ATG) or solumederol and cytomegalovirus infection (CMV) 90 days pre or post bacteremia, recurrent urinary tract infections (UTI), source of bacteremia and microbiology, all-cause mortality at day 28 and graft function at the last follow up were noted. Results: Out of 1009 RTR, 33 (3.3%) episodes of GNB occurred. The mean age was 30±11.85years, 61% males. Around 48% developed bacteremia within 6 months post-transplant. The most common source was UTI (75.8%). Fever in 48% and only 39% had leukocytosis. Around 9% were admitted in the intensive care unit. E-coli was the most common organism (70%) (Table 1). Stone disease at the time of transplant was significantly associated with bacteremia (p=0.029). There was no difference in receiving ATG or solumeredol and CMV before bacteremia. A significant number of patients received solumeredol for rejection (p=0.035) and had CMV (p=0.044) within 90 days after bacteremia. Recurrent UTI is significantly associated with bacteremia (p<0.001). The graft function at the last follow-up (2 years) was significantly deranged in patients with bacteremia (p=0.0001). Conclusion: Gram-negative bacteremia was found in 3% of RTR and half of them developed within 6 months post-transplant. UTI was the most common source and recurrent UTI was significantly associated with bacteremia. The stone disease was the most significant risk factor. Patients develop rejection and CMV infection within 3 months post bacteremia. There was a significant graft dysfunction among patients with bacteremia at a mean follow-up of 2 years. We need to focus on the management of recurrent UTIs to prevent bacteremia and graft dysfunction in renal transplant recipients.

Molecular epidemiology and antimicrobial resistance phenotype of paediatric bloodstream infections caused by Gram-negative bacteria

BackgroundGram-negative organisms are common causes of bloodstream infection (BSI) during the neonatal period and early childhood. Whilst several large studies have characterised these isolates in adults, equivalent data (particularly incorporating whole genome sequencing) is lacking in the paediatric population.MethodsWe perform an epidemiological and sequencing based analysis of Gram-negative bloodstream infections (327 isolates (296 successfully sequenced) from 287 patients) in children <18 years old between 2008 and 2018 in Oxfordshire, UK.ResultsHere we show that the burden of infection lies predominantly in neonates and that most infections are caused by Escherichia coli, Klebsiella spp. and Enterobacter hormaechei. There is no evidence in our setting that the proportion of antimicrobial resistant isolates is increasing in the paediatric population although we identify some evidence of sub-breakpoint increases in gentamicin resistance. The population structure of E. coli BSI isolates in neonates and children mirrors that in adults with a predominance of STs 131/95/73/69 and the same proportions of O-antigen serotypes. In most cases in our setting there is no evidence of transmission/point-source acquisition and we demonstrate the utility of whole genome sequencing to refute a previously suspected outbreak.ConclusionsOur findings support continued use of current empirical treatment guidelines and suggest that O-antigen targeted vaccines may have a role in reducing the incidence of neonatal sepsis.

Update on Staphylococcus aureus bacteraemia.

To review recently published evidence relevant to Staphylococcus aureus bacteremia (SAB). Staphylococcus aureus is the most common pathogen causing co-infections and superinfections in patients with COVID-19. Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia ratios have sharply risen during the pandemic. SAB mortality is 18% at 1 month and 27% at 3 months but has gradually decreased over the last 30 years. Recurrences and reinfections are common (9%). Standardised items to define complicated SAB, and a new cut-off defining persisting bacteremia after 2 days with positive blood cultures have been proposed. Multiple antibiotic combinations have been trialled including vancomycin or daptomycin with β-lactams, fosfomycin, or clindamycin, without significant results. In the recently published guidelines, vancomycin remains the first line of treatment for MRSA bacteremia. For the management of methicillin-susceptible Staphylococcus aureus , cefazolin less frequently causes acute kidney injury than flucloxacillin, and when susceptibility is demonstrated, de-escalation to penicillin G is suggested. Our review confirms that Staphylococcus aureus represents a special aetiology among all causes of bloodstream infections. Pending results of platform and larger trials, its distinct epidemiology and determinants mandate careful integration of clinical variables and best available evidence to optimize patient outcomes.

Molecular Determination of Virulence Factor Genes of Acinetobacter baumannii Isolates from Clinical Specimens

Acinetobacter baumannii is a gram negative coccobacilli present abundantly in nature, in soil and water. Acinetobacter baumannii is considered as a major cause of nosocomial infections affecting mainly ICU patients and other hospitalised patients. Both intrinsic and acquired antibiotic resistance of A. baumannii account for a significant cause of outbreaks. Significant levels of morbidity and mortality have been reported with outbreaks and common infections include ventilator associated pneumonia and bacteraemia. A.baumannii is also a common cause of bloodstream infections in the intensive care setting. Multiple virulence factors are required for the pathogenesis of infections by Gram negative bacteria including A. baumannii. Possession of specialized virulence genes enables pathogens to infect hosts efficiently. Virulence factors of A. baumannii were less identified compared to other Gram negative bacteria. Hence this study was done to identify the major virulence factor genes from the clinical isolates of multidrug resistant A. baumannii from a tertiary care hospital. A preliminary study was done to determine the prevalence of Acinetobacter infections in the region and then the isolates were subjected to determine the antibiotic sensitivity and to various molecular typing. Various clinical specimens like blood, urine, abscess, vaginal swab were analyzed and 15% of the isolates was confirmed and identified as to be resistant to carbapenems. A molecular typing was done to identify the genes conferring virulence factors. Presence of different genes like Bap, Omp A, EpsA, ptk, AdeG were screened from the isolates. : , , , ,

The Relationship Between Antibiotic Agent and Mortality in Patients With Febrile Neutropenia due to Staphylococcal Bloodstream Infection: A Multicenter Cohort Study.

BackgroundMethicillin-susceptible Staphylococcus aureus (MSSA) is a common cause of bloodstream infection (BSI) in patients with febrile neutropenia, but treatment practices vary, and guidelines are not clear on the optimal regimen.MethodsWe conducted a multicenter retrospective cohort study of MSSA BSI in febrile neutropenia. We divided patients into 3 treatment groups: (1) broad-spectrum beta-lactams (ie, piperacillin-tazobactam, cefepime, meropenem); (2) narrow-spectrum beta-lactams (ie, cefazolin, oxacillin, nafcillin); and (3) combination beta-lactams (ie, both narrow- and broad-spectrum). We used multivariable logistic regression to compare 60-day mortality and bacteremia recurrence while adjusting for potential confounders.ResultsWe identified 889 patients with MSSA BSI, 128 of whom had neutropenia at the time of the index culture: median age 56 (interquartile range, 43–65) years and 76 (59%) male. Of those, 56 (44%) received broad-spectrum beta-lactams, 30 (23%) received narrow-spectrum beta-lactams, and 42 (33%) received combination therapy. After adjusting for covariates, including disease severity, combination therapy was associated with a significantly higher odds for 60-day all-cause mortality compared with broad spectrum beta-lactams (adjusted odds ratio [aOR], 3.39; 95% confidence interval [CI], 1.29–8.89; P = .013) and compared with narrow spectrum beta-lactams, although the latter was not statistically significant (aOR, 3.30; 95% CI, .80–13.61; P = .071).ConclusionsUse of combination beta-lactam therapy in patients with MSSA BSI and febrile neutropenia is associated with a higher mortality compared with treatment with broad-spectrum beta-lactam after adjusting for potential confounders. Patients in this study who transitioned to narrow-spectrum beta-lactam antibiotics did not have worse clinical outcomes compared with those who continued broad-spectrum beta-lactam therapy.

Risk Factors and Outcomes of Acute Graft Pyelonephritis with Bacteremia Due to Multidrug-Resistant Gram-Negative Bacilli among Kidney Transplant Recipients.

Acute graft pyelonephritis (AGP) is the leading cause of bloodstream infection in kidney transplant (KT) recipients. The prevalence of urinary tract infections caused by multidrug-resistant (MDR) Gram-negative bacilli is increasing. This 14-year prospective observational study sought to determine the clinical characteristics, risk factors, and outcomes of AGP with bacteremia due to MDR Gram-negative bacilli. Overall, 278 episodes of AGP with bacteremia due to MDR Gram-negative and non-MDR Gram-negative bacilli were identified and compared in 214 KT recipients; MDR Gram-negative bacilli were the cause in 28.4%. Overall 30-day mortality was low (1.1%). Risk factors independently associated with AGP due to MDR Gram-negative bacilli were male sex (OR 3.08; 95%CI 1.60–5.93), previous episode of bacteremic AGP (OR 2.11, 95%CI 1.09–4.09), prior antibiotic therapy in the preceding month (OR 2.47, 95%CI 1.33–4.57), and nosocomial acquisition (OR 2.03, 95%CI 1.14–3.62). Forty-three percent of MDR Gram-negative episodes received inappropriate empirical antibiotic therapy. The risk factors identified in this study may help physicians when selecting empirical antibiotic treatment for AGP. Previous antibiotic use was the main modifiable factor. Its presence highlights the importance of avoiding unnecessary antibiotics in order to bring down the high rates of MDR Gram-negative bacilli infections in this population.

Medical microbiology

Candida species are the fourth most common cause of bloodstream infections and are the leading cause of invasive fungal infections among hospitalized patients [1]. Candidemia is a life-threatening fungal infection associated with a mortality rate of 38%; [2].The spectrum of candidemia has changed with the emergence of non- albicans Candida (NCAC) species, a strain with the threat of increased mortality especially in immunocompromised and severely ill patients [4]. It is very important to identify Candida to the species level to optimize the selection of the antifungal agent. More importantly, intrinsic and emerging resistance represents a major challenge for empirical, therapeutic and prophylactic strategies. Candida species have also been isolated from the respiratory tract, mouth, skin, ear and eye. Candida is a true opportunistic pathogen that under certain circumstances is able to invade tissues normally resistant to infection.