Bacterial etiology and antimicrobial resistance pattern of pediatric bloodstream infections: a 5-year experience in an Iranian referral hospital.

BACKGROUND: Bloodstream infections (BSI) are the major cause of morbidity and mortality in children in developing countries. The purpose of the current study was to establish the antimicrobial susceptibility pattern of bacterial isolates from bloodstream infections at Children's Medical Center Hospital (CMC), Tehran, Iran. METHODS: We retrospectively recorded all positive blood cultures and antimicrobial susceptibility of all bloodstream isolates among children admitted to CMC, during 5 years. Specimen culture, bacterial identification, and antimicrobial susceptibility testing were performed according to standard laboratory methods. RESULTS: From 3,179 pathogens isolated from the blood cultures 2,824 bacteria were cultured, with 1,312 cases being identified as Gram-positive bacteria (46%) and 1,512 cases as Gram-negative bacteria (54%). The most common Gram-negative bacteria isolated were as follows: Pseudomonas spp. (n = 266, 17.6%), Klebsiella pneumoniae (n = 242, 16%), Stenotrophomonas maltophilia (n = 204, 13.5%), Enterobacter spp. (n = 164, 10.8%), Escherichia coli (n = 159, 10.5%), Pseudomonas aeruginosa (n = 126, 8.3%), Serratia marcescens (n = 121, 8%), and Acinetobacter baumannii (n = 73, 4.8%). The most common Gram-positive bacteria isolated were coagulase-negative staphylococci (CONS) (n = 697, 53%), Streptococcus spp. (n = 237, 18%), Staphylococcus aureus (n = 202, 15%) and Enterococcus spp. (n = 167, 12.7%). 34% of bacterial strains were isolated from ICUs. The rates of methicillin resistance in S. aureus and CONS were 34% and 91%, respectively. E. coli isolates showed high resistance to cefotaxime (84%). All isolates of K. pneumoniae were susceptible to colistin and 56% were susceptible to imipenem. P. aeruginosa isolates showed high susceptibility to all antibiotics. CONCLUSIONS: Our findings emphasize the need of clinicians having access to up-to-date bacterial susceptibility data for routinely prescribed drugs. Continuous monitoring of changes in bacterial resistance will aid in the establishment of national priorities for local intervention initiatives in Iran. The increased risk of BSI caused by antibiotic-resistant organisms, emphasizes the significance of implementing appropriate antibiotic prescribing regulations and developing innovative vaccination techniques in Iran.

A Rare Cause of Empyema and Bacteremia Due to Shewanella Species in Alcoholic Cirrhosis Patients: A Case Report and Comprehensive Review of Literature.

BACKGROUND Shewanella spp. are gram-negative facultative anaerobic, oxidase-positive, motile bacilli that are ubiquitous but commonly occur in seawater and can cause opportunistic infection. Reports on the risk factors for Shewanella infection, its severity, antibiotic susceptibility, and prognosis are limited. This report is of a 78-year-old man with alcoholic cirrhosis presenting with bacteremia and empyema due to infection with Shewanella spp. CASE REPORT A 78-year-old man with alcoholic cirrhosis (Child-Pugh B) presented to our emergency room with a high fever. He had eaten raw fish one week prior to admission. Chest computed tomography showed a right unilateral pleural effusion, and he was hospitalized with suspected empyema. Shewanella spp. was detected in the pleural effusion and blood cultures. We initiated piperacillin/tazobactam and vancomycin empirically and switched to ceftriaxone; the effusion was successfully treated using antibiotics and pleural drainage. However, on hospitalization day 53, the patient died of aspiration pneumonia. In our literature review, we extracted 125 reported cases (including our case) and found that men were disproportionately affected (81%); median age was 61.6 (56-75) years; underlying diseases included hepatobiliary disease (33%), malignancy (25%), and cardiac disease (24%); Shewanella spp. infection sites were skin and soft tissue (35%), respiratory system (18%), and hepatobiliary system (11%); and management included antibiotics (100%), drainage (16%), and debridement (16%). The survival rate was 74% with antibiotics alone. CONCLUSIONS Our case highlights that clinicians should recognize Shewanella spp. as a cause of empyema and bacteremia in patients with liver cirrhosis, and that microbiological diagnosis with antibiotic sensitivity testing and treatment should be undertaken urgently to prevent fatal sepsis.

Polymicrobial bloodstream infections a risk factor for mortality in neonates at the national hospital, Tanzania: A case-control study.

BACKGROUND: Polymicrobial bloodstream infections (BSI) are difficult to treat since empiric antibiotics treatment are frequently less effective against multiple pathogens. The study aimed to compare outcomes in patients with polymicrobial and monomicrobial BSIs. METHODS: The study was a retrospective case-control design conducted at Muhimbili National Hospital for data processed between July 2021 and June 2022. Cases were patients with polymicrobial BSI, and controls had monomicrobial BSI. Each case was matched to three controls by age, admitting ward, and duration of admission. Logistic regression was performed to determine independent risk factors for in-hospital and 30-day mortality. RESULTS: Fifty patients with polymicrobial BSI and 150 with monomicrobial BSI were compared: the two arms had no significant differences in sex and comorbidities. The most frequent bacteria in polymicrobial BSI were Klebsiella pneumoniae 17% (17/100) and Enterobacter species 15% (15/100). In monomicrobial BSI, S. aureus 17.33% (26/150), Klebsiella pneumoniae 16.67% (25/150), and Acinetobacter species 15% (15/150) were more prevalent. Overall, isolates were frequently resistant to multiple antibiotics tested, and 52% (130/250) were multidrug resistance. The 30-day and in-hospital mortality were 33.5% (67/200) and 36% (72/200), respectively. On multivariable analysis, polymicrobial BSIs were independent risk factors for both in-hospital mortality (aOR 2.37, 95%CI 1.20-4.69, p = 0.01) and 30-day mortality (aOR 2.05, 95%CI 1.03-4.08), p = 0.04). In sub-analyses involving only neonates, polymicrobial BSI was an independent risk factor for both 30-day mortality (aOR 3.13, 95%CI 1.07-9.10, p = 0.04) and in-hospital mortality (aOR 5.08, 95%CI 1.60-16.14, p = 0.006). Overall, the median length of hospital stay post-BSIs was numerically longer in patients with polymicrobial BSIs. CONCLUSION: Overall, polymicrobial BSI was a significant risk for mortality. Patients with polymicrobial BSI stay longer at the hospital than those with monomicrobial BSI. These findings call for clinicians to be more aggressive in managing polymicrobial BSI.

Prospective observational pilot study of the T2Resistance panel in the T2Dx system for detection of resistance genes in bacterial bloodstream infections.

Early initiation of antimicrobial therapy targeting resistant bacterial pathogens causing sepsis and bloodstream infections (BSIs) is critical for a successful outcome. The T2Resistance Panel (T2R) detects the following resistance genes within organisms that commonly cause BSIs directly from patient blood samples: blaKPC, blaCTXM-14/15, blaNDM/bla/IMP/blaVIM, blaAmpC, blaOXA, vanA, vanB, and mecA/mecC. We conducted a prospective study in two major medical centers for the detection of circulating resistance genes by T2R in patients with BSIs. T2R reports were compared to antimicrobial susceptibility testing (AST), phenotypic identification, and standard molecular detection assays. Among 59 enrolled patients, 25 resistance genes were identified: blaKPC (n = 10), blaNDM/bla/IMP/blaVIM (n = 5), blaCTXM-14/15 (n = 4), blaAmpC (n = 2), and mecA/mecC (n = 4). Median time-to-positive-T2R in both hospitals was 4.4 hours [interquartile range (IQR): 3.65-4.97 hours] in comparison to that for positive blood cultures with final reporting of AST of 58.34 h (IQR: 45.51-111.2 hours; P < 0.0001). The sensitivity of T2R to detect the following genes in comparison to AST was 100% for blaCTXM-14/15, blaNDM/bla/IMP/blaVIM, blaAmpC, mecA/mecC and 87.5% for blaKPC. When monitored for the impact of significant antimicrobial changes, there were 32 events of discontinuation of unnecessary antibiotics and 17 events of escalation of antibiotics, including initiation of ceftazidime/avibactam in six patients in response to positive T2R results for blaKPC. In summary, T2R markers were highly sensitive for the detection of drug resistance genes in patients with bacterial BSIs, when compared with standard molecular resistance detection systems and phenotypic identification assays while significantly reducing by approximately 90% the time to detection of resistance compared to standard methodology and impacting clinical decisions for antimicrobial therapy. IMPORTANCE: This is the first reported study to our knowledge to identify key bacterial resistance genes directly from the bloodstream within 3 to 5 hours in patients with bloodstream infections and sepsis. The study further demonstrated a direct effect in modifying initial empirical antibacterial therapy in response to T2R signal to treat resistant bacteria causing bloodstream infections and sepsis.

Gardnerella Vaginalis Bacteremia in a Pregnant Woman with Vaginal Myomectomy.

BACKGROUND: This case involves a 28-year-old pregnant woman (39w+2) who was admitted to obstetrics due to abdominal tightness and bacteremia with Gardnerella vaginalis which developed after caesarean section and vaginal myomectomy. METHODS: A blood culture was performed, and the bacteria were identified through mass spectrometry. RESULTS: Mass spectrometry data indicated that the infection bacteria were Gardnerella vaginalis. The patient's temperature returned to normal after oral ampicillin in combination with clindamycin. CONCLUSIONS: Gardnerella vaginalis bacteremia is very rare in clinical practice, and the combination of ampicillin and clindamycin has a good therapeutic effect. This study may provide a reference for the diagnosis and treatment of Gardnerella vaginalis bacteremia.

Clinical characteristics and risk factors for Klebsiella pneumoniae bloodstream infection in 152 immunocompetent patients.

OBJECTIVE: To investigate the clinical characteristics and prognostic risk factors for Klebsiella pneumoniae bloodstream infections in immunocompetent patients. METHODS: The study included patients with K. pneumoniae bloodstream infection treated in Zhongda Hospital from June 2016 to June 2021. Clinical data and antibiotic susceptibility test results were retrospectively collected and analyzed. Independent risk factors for mortality were screened using the chi-square test and multivariate logistic regression. RESULTS: A total of 152 patients were included in the analysis. In our cohort, 77.6% of patients were older than 60 years, and 80.9% of them had community-acquired infections. The most common complications were type 2 diabetes, hypertension, and stroke sequelae. The proportion of patients with septic shock or abscesses was 34.9% and 25.7%, respectively. There were significant differences in the site of infection, septic shock, and serum levels of procalcitonin, hypersensitive C-reactive protein, D-dimer, creatinine, and lactic acid between survivors and non-survivors (p < 0.05). Multivariate regression analysis showed that hospital-acquired infections, septic shock, length of hospital stay, and creatinine levels were independent risk factors for mortality. Antibiotic susceptibility test results indicated that clinical outcomes varied depending on bacterial sensitivity to ampicillin/sulbactam. DISCUSSION: Klebsiella pneumoniae is a common community-acquired and hospital-acquired bacteria and usually infects older people with complications such as diabetes. Nosocomial infections, length of stay, septic shock, and renal insufficiency are potentially associated with poor prognosis. Bacterial susceptibility to ampicillin/sulbactam affects prognosis.

Epidemiology and outcomes associated with enterococcal blood stream infection among liver and kidney transplant recipients.

Bloodstream infections (BSIs) account for 18% of bacterial infections in the first year after solid organ transplantation (SOT). Enterococcus accounts for up to 20% of BSIs in this population, with vancomycin-resistant enterococcus (VRE) posing a particular risk. This is a retrospective, case-control study of adult liver and kidney transplant recipients between 01/01/2016 and 06/30/2021 that characterizes the epidemiology and outcomes of enterococcal BSIs in liver and kidney transplantations at a single institution. Subjects with an enterococcal BSI within the first 6 months post-transplant were compared to those with non-enterococcal BSIs in the same period. We identified 26 subjects with enterococcal BSIs and 28 controls with non-enterococcal BSIs (n = 54; 10.3%). Cases were mostly liver transplant recipients (n = 20; 77%) with a median MELD at transplant of 33 (range 14-43); controls included 14 KT recipients (50%). Groups differed significantly (all p < .05) by factors including perioperative transfusion requirements, need for reoperation, and number of interventions post-transplant. Cases had a median time of 25.5 days to infection and controls 100.5 days (p < .0001). There were no differences in 1-year mortality between the groups. Enterococcus faecium was the predominant species of Enterococcus (n = 23; 88.5%), with a majority (91.3%) of the isolates being VRE. In our liver and kidney transplants, enterococcal BSIs occurred early among liver transplant recipients. The high incidence of VRE among E. faecium isolates in this population warrants further investigation into the optimal approach to empiric antimicrobials for bacteremia in the early post-transplant period.

Whole-genome characterisation of Escherichia coli isolates from patients with bacteraemia presenting with sepsis or septic shock in Spain: a multicentre cross-sectional study.

BACKGROUND: Escherichia coli is the most frequent cause of bloodstream infections (BSIs). About one-third of patients with BSIs due to E coli develop sepsis or shock. The objective of this study is to characterise the microbiological features of E coli blood isolates causing sepsis or septic shock to provide exploratory information for future diagnostic, preventive, or therapeutic interventions. METHODS: E coli blood isolates from a multicentre cross-sectional study of patients older than 14 years presenting with sepsis or septic shock (according to the Third International Consensus Definitions for Sepsis and Septic Shock criteria) from hospitals in Spain between Oct 4, 2016, and Oct 15, 2017, were studied by whole-genome sequencing. Phylogroups, sequence types (STs), serotype, FimH types, antimicrobial resistance (AMR) genes, pathogenicity islands, and virulence factors were identified. Susceptibility testing was performed by broth microdilution. The main outcome of this study was the characterisation of the E coli blood isolates in terms of population structure by phylogroups, groups (group 1: phylogroups B2, F, and G; group 2: A, B1, and C; group 3: D), and STs and distribution by geographical location and bloodstream infection source. Other outcomes were virulence score and prevalence of virulence-associated genes, pathogenicity islands, AMR, and AMR-associated genes. Frequencies were compared using χ² or Fisher's exact tests, and continuous variables using the Mann-Whitney test, with Bonferroni correction for multiple comparisons. FINDINGS: We analysed 224 isolates: 140 isolates (63%) were included in phylogenetic group 1, 52 (23%) in group 2, and 32 (14%) in group 3. 85 STs were identified, with four comprising 44% (n=98) of the isolates: ST131 (38 [17%]), ST73 (25 [11%]), ST69 (23 [10%]), and ST95 (12 [5%]). No significant differences in phylogroup or ST distribution were found according to geographical areas or source of bloodstream infection, except for ST95, which was more frequent in urinary tract infections than in other sources (11 [9%] of 116 vs 1 [1%] of 108, p=0·0045). Median virulence score was higher in group 1 (median 25·0 [IQR 20·5-29·0) than in group 2 (median 14·5 [9·0-20·0]; p<0·0001) and group 3 (median 21 [16·5-23·0]; p<0·0001); prevalence of several pathogenicity islands was higher in group 1. No significant differences were found between phylogenetic groups in proportions of resistance to antibiotics. ST73 had higher median virulence score (32 [IQR 29-35]) than the other predominant clones (median range 21-28). Some virulence genes and pathogenicity islands were significantly associated with each ST. ST131 isolates had higher prevalence of AMR and a higher proportion of AMR genes, notably blaCTX-M-15 and blaOXA-1. INTERPRETATION: In this exploratory study, the population structure of E coli causing sepsis or shock was similar to previous studies that included all bacteraemic isolates. Virulence genes, pathogenicity islands, and AMR genes were not randomly distributed among phylogroups or STs. These results provide a comprehensive characterisation of invasive E coli isolates causing severe response syndrome. Future studies are required to determine the contribution of these microbiological factors to severe clinical presentation and worse outcomes in patients with E coli bloodstream infection. FUNDING: Instituto de Salud Carlos III.

Evaluation of three protocols for direct susceptibility testing for Gram-negative rods from flagged positive blood culture bottles.

Bloodstream infections are associated with high mortality, which can be reduced by targeted antibiotic therapy in the early stages of infection. Direct antibiotic susceptibility testing (AST) from flagged positive blood cultures may facilitate the administration of early effective antimicrobials much before the routine AST. This study aimed to evaluate three different direct AST protocols for Gram-negative rods from flagged positive blood culture broths. Blood culture broths showing Gram-negative rods only were subjected to direct AST by Clinical and Laboratory Standards Institute-recommended direct disk diffusion (protocol A). Additionally, automated AST (protocol B) and Kirby-Bauer disk diffusion (protocol C) were performed with standard inoculum prepared from bacterial pellets obtained by centrifuging blood culture broths in serum separator vials. For comparison, conventional AST of isolates from solid media subculture was also performed with Kirby-Bauer disk diffusion (reference standard) and the automated method. Overall, categorical agreements of protocols A, B, and C were 97.6%, 95.7%, and 95.9%, respectively. Among Enterobacterales, minor error, major error, and very major error rates of protocol B were 3.5%, 0.36%, and 0.43%, respectively, whereas minor error, major error, and very major error rates of protocol C were 3.4%, 0.72%, and 0.21%, respectively, and among non-fermenters, protocol B had a minor error rate of 6.5%, and protocol C had a minor error rate of 4.1% and major error rate of 1.9%. All three direct AST protocols demonstrated excellent categorical agreements with the reference method. Performance of protocols B and C between Enterobacterales and non-fermenters was not statistically different. IMPORTANCE: Bloodstream infections are associated with high mortality that can be reduced by targeted antibiotic therapy in the early stages of infection. Direct antibiotic susceptibility testing (AST) from flagged positive blood cultures may facilitate the administration of early effective antimicrobials much before the routine AST. Clinical and Laboratory Standards Institute-recommended direct AST can be performed with a limited number of antibiotic disks only. On the other hand, using an automated system for direct AST will not only allow effective laboratory workflow with reduced turnaround time but also provide the minimum inhibitory concentration values of tested antibiotics. However, using expensive automated systems for direct AST may not be feasible for resource-limited laboratories. Therefore, in this study, we aimed to evaluate the CLSI-recommended method and two other direct AST protocols (one with an automated system and the other with disk diffusion) for Gram-negative rods from flagged positive blood cultures.

Cefepime-Taniborbactam in Complicated Urinary Tract Infection.

BACKGROUND: Carbapenem-resistant Enterobacterales species and multidrug-resistant Pseudomonas aeruginosa are global health threats. Cefepime-taniborbactam is an investigational ß-lactam and ß-lactamase inhibitor combination with activity against Enterobacterales species and P. aeruginosa expressing serine and metallo-ß-lactamases. METHODS: In this phase 3, double-blind, randomized trial, we assigned hospitalized adults with complicated urinary tract infection (UTI), including acute pyelonephritis, in a 2:1 ratio to receive intravenous cefepime-taniborbactam (2.5 g) or meropenem (1 g) every 8 hours for 7 days; this duration could be extended up to 14 days in case of bacteremia. The primary outcome was both microbiologic and clinical success (composite success) on trial days 19 to 23 in the microbiologic intention-to-treat (microITT) population (patients who had a qualifying gram-negative pathogen against which both study drugs were active). A prespecified superiority analysis of the primary outcome was performed after confirmation of noninferiority. RESULTS: Of the 661 patients who underwent randomization, 436 (66.0%) were included in the microITT population. The mean age of the patients was 56.2 years, and 38.1% were 65 years of age or older. In the microITT population, 57.8% of the patients had complicated UTI, 42.2% had acute pyelonephritis, and 13.1% had bacteremia. Composite success occurred in 207 of 293 patients (70.6%) in the cefepime-taniborbactam group and in 83 of 143 patients (58.0%) in the meropenem group. Cefepime-taniborbactam was superior to meropenem regarding the primary outcome (treatment difference, 12.6 percentage points; 95% confidence interval, 3.1 to 22.2; P = 0.009). Differences in treatment response were sustained at late follow-up (trial days 28 to 35), when cefepime-taniborbactam had higher composite success and clinical success. Adverse events occurred in 35.5% and 29.0% of patients in the cefepime-taniborbactam group and the meropenem group, respectively, with headache, diarrhea, constipation, hypertension, and nausea the most frequently reported; the frequency of serious adverse events was similar in the two groups. CONCLUSIONS: Cefepime-taniborbactam was superior to meropenem for the treatment of complicated UTI that included acute pyelonephritis, with a safety profile similar to that of meropenem. (Funded by Venatorx Pharmaceuticals and others; CERTAIN-1 ClinicalTrials.gov number, NCT03840148.).

Performance of the 2023 Duke-International Society of Cardiovascular Infectious Diseases Diagnostic Criteria for Infective Endocarditis in Relation to the Modified Duke Criteria and to Clinical Management-Reanalysis of Retrospective Bacteremia Cohorts.

BACKGROUND: Revised diagnostic criteria for infective endocarditis (IE), the 2023 Duke-ISCVID criteria, were recently presented and need validation. Here, we compare the 2000 modified Duke criteria for IE with Duke-ISCVID among patients with bacteremia and relate the diagnostic classification to IE treatment. METHODS: We reanalyzed patient cohorts with Staphylococcus aureus, Staphylococcus lugdunensis, non-ß-hemolytic streptococci, Streptococcus-like bacteria, Streptococcus dysgalactiae, Enterococcus faecalis, and HACEK (Haemophilus, Aggregatibacter, Cardiobacterium, Eikenella, Kingella) bacteremia. Episodes were classified as definite, possible, or rejected IE with the modified Duke and Duke-ISCVID criteria. Reclassification included the microbiology criteria, positron emission tomography-computed tomography, and cardiac implanted electronic devices. To calculate sensitivity, patients treated for IE were considered as having IE. RESULTS: In 4050 episodes of bacteremia, the modified Duke criteria assigned 307 episodes (7.6%) as definite IE, 1190 (29%) as possible IE, and 2553 (63%) as rejected IE. Using the Duke-ISCVID criteria, 13 episodes (0.3%) were reclassified from possible to definite IE, and 475 episodes (12%) were reclassified from rejected to possible IE. With the modified Duke criteria, 79 episodes that were treated as IE were classified as possible IE, and 11 of these episodes were reclassified to definite IE with Duke-ISCVID. Applying the decision to treat for IE as a reference standard, the sensitivity of the Duke-ISCVID criteria was 80%. None of the 475 episodes reclassified to possible IE were treated as IE. CONCLUSIONS: The Duke-ISCVID criteria reclassified a small proportion of episodes to definite IE at the expense of more episodes of possible IE. Future criteria should minimize the possible IE group while keeping or improving sensitivity.

Bacteriophage and antibiotic combination therapy for recurrent Enterococcus faecium bacteremia.

Enterococcus faecium is a member of the human gastrointestinal (GI) microbiota but can also cause invasive infections, especially in immunocompromised hosts. Enterococci display intrinsic resistance to many antibiotics, and most clinical E. faecium isolates have acquired vancomycin resistance, leaving clinicians with a limited repertoire of effective antibiotics. As such, vancomycin-resistant E. faecium (VREfm) has become an increasingly difficult to treat nosocomial pathogen that is often associated with treatment failure and recurrent infections. We followed a patient with recurrent E. faecium bloodstream infections (BSIs) of increasing severity, which ultimately became unresponsive to antibiotic combination therapy over the course of 7 years. Whole-genome sequencing (WGS) showed that the patient was colonized with closely related E. faecium strains for at least 2 years and that invasive isolates likely emerged from a large E. faecium population in the patient's gastrointestinal (GI) tract. The addition of bacteriophage (phage) therapy to the patient's antimicrobial regimen was associated with several months of clinical improvement and reduced intestinal burden of VRE and E. faecium. In vitro analysis showed that antibiotic and phage combination therapy improved bacterial growth suppression compared to therapy with either alone. Eventual E. faecium BSI recurrence was not associated with the development of antibiotic or phage resistance in post-treatment isolates. However, an anti-phage-neutralizing antibody response occurred that coincided with an increased relative abundance of VRE in the GI tract, both of which may have contributed to clinical failure. Taken together, these findings highlight the potential utility and limitations of phage therapy to treat antibiotic-resistant enterococcal infections. IMPORTANCE: Phage therapy is an emerging therapeutic approach for treating bacterial infections that do not respond to traditional antibiotics. The addition of phage therapy to systemic antibiotics to treat a patient with recurrent E. faecium infections that were non-responsive to antibiotics alone resulted in fewer hospitalizations and improved the patient's quality of life. Combination phage and antibiotic therapy reduced E. faecium and VRE abundance in the patient's stool. Eventually, an anti-phage antibody response emerged that was able to neutralize phage activity, which may have limited clinical efficacy. This study demonstrates the potential of phages as an additional option in the antimicrobial toolbox for treating invasive enterococcal infections and highlights the need for further investigation to ensure phage therapy can be deployed for maximum clinical benefit.

Outbreak investigation of Serratia marcescens bloodstream infection in an obstetric ward for high-risk pregnant women.

BACKGROUND: Serratia marcescens is a gram-negative bacterium that is widespread in the environment. S. marcescens bacteremia can be fatal during pregnancy and cause persistent chorioamnionitis. This study reports an outbreak of Serratia marcescens bloodstream infection (BSI) among high-risk pregnant women in an obstetric ward. The purpose of this study is to report our experience with the usefulness of the ATP test in hospital environmental management and to confirm that bloodstream infections of patients with the same strain were correlated by WGS testing. METHODS: This retrospective study collected the data of inpatients with S. marcescens bacteremia in obstetric ward for high-risk pregnant women from August 22, 2021, to October 14, 2021. We performed: an adenosine triphosphate (ATP) bioluminescence test in the environment with a high-contact area; environmental culture; on-site monitoring and staff education; and whole-genome sequencing (WGS) to evaluate genetic relationships among S. marcescens isolates. RESULTS: S. marcescens BSI occurred in four consecutive patients. None of the patients had central venous catheters. An ATP bioluminescence test revealed that high-contact areas and areas for injection preparation were not clean (≥ 1000 relative light units). However, S. marcescens was not identified in the environmental cultures, likely due to intensive environmental cleaning and discarding of potentially contaminated specimens before the culture test. On-site monitoring and education were conducted for 1 month. There were no further reports of BSI until 6 months after the last patient was discharged. WGS performed on three isolates from three patients indicated that the isolated S. marcescens was likely from the same strain. CONCLUSIONS: We controlled an S. marcescens outbreak by improving environmental cleaning as well as education of and behavior changes in healthcare workers. Using the ATP bioluminescence test can provide feedback on environmental cleaning and education. WGS played a role in determining the spread of BSI caused by the same strain.

Bacterial Isolates and Characteristics of Children With Febrile Neutropenia on Treatment for Cancer at a Tertiary Hospital in Western Kenya.

PURPOSE: This study aimed to identify the patient characteristics of children with febrile neutropenia, the associated bacterial organisms, and their sensitivity patterns. MATERIALS AND METHODS: A descriptive cross-sectional study was conducted at the Moi Teaching and Referral Hospital (MTRH) pediatric oncology ward, from June 2021 to April 2022. A total of 110 children who developed fever and neutropenia during chemotherapy were enrolled. Blood samples for culture were collected aseptically. Patient characteristics were presented in frequency tables. Antimicrobial sensitivity patterns were plotted in tables against the bacterial isolates cultured. Chi-square/Fisher's exact test was used to determine any association between patient characteristics, bacterial growth, and antimicrobial sensitivity. RESULTS: The majority (n = 66; 60%) were males. The median age was 6.3 years (standard deviation, 3.7). The majority of patients 71 (64.5%) had hematologic malignancies, the most common being AML. There was a significant association between severity of neutropenia and hematologic malignancies (P = .028). In total, 31/110 (28.2%) blood cultures were positive for bacterial growth. Gram-positive bacteria were more frequent (n = 20; 58.1%). The most common organism was Escherichia coli (n = 6; 18.2%), followed by Staphylococcus aureus (n = 5; 15.2%). All the isolates were sensitive to linezolid and vancomycin and also showed good sensitivity toward meropenem (n = 10/11; 90.9%). High resistance to cephalosporins was noted with ceftriaxone (n = 5/6; 83.3%), cefepime (n = 4/7; 57.1%), and ceftazidime (n = 3/4; 75%). CONCLUSION: The most common malignancy associated with febrile neutropenia was AML. Gram-positive bacteria were the most common isolates. There was high resistance to cephalosporins.

New Antibiotic Binding Resin Bottles Collected from Children Enhances Rapid Microbial Identification.

BACKGROUND: Bloodstream infections (BSI) represent a common cause of sepsis and mortality in children. Blood culture (BC) is the gold standard for diagnosis of BSI. The low sensitivity of BC in the pediatric population is usually due to the small volume of blood used for inoculation and to the antibiotics used before sampling. Here, we explore the ways to effectively reduce antibiotic activity to maximize the chances of pathogen recovery, and to enhance the growth of microorganisms in lower blood volume and bacterial counts. METHODS: The recovery of common pathogens causing blood stream infections was analyzed after exposure to cefo-perazone/sulbactam, vancomycin, and caspofung by using resin-containing or not BacT/Alert PF Plus and BD FX400 peds plus pediatric bottles. The microbial growth in the resin-containing bottles was assessed using 0.5 colony-forming units (CFU) bacterial inoculum to mimic the bacteremia/fungemia condition. The usefulness of a diagnosis to confirm or exclude BSI was evaluated by lower than recommended blood culture sampling (102 CFU/mL, 0.3 mL). RESULTS: Staphylococcus aureus (S. aureus), and Candida glabrata (C. glabrata) were recovered from 100% of two types of resin-containing bottles in the presence of a sufficient antibiotic dose, while Escherichia coli (E. coli) was not restored to 100% in BD FX400 peds plus pediatric bottles. The shorter TTD for S. aureus, C. glabrata, and E. coli were observed in antibiotic-containing BacT/Alert PF Plus bottles. Both the PF Plus and BD resin test bottles showed consistently good TTD performances to Gram-negative, Gram-positive, and yeast species in low inoculum levels, with the exception of S. aureus. The lower volume of blood inoculated into culture bottles hardly affected the growth of most bacteria, but optimized PF Plus resin-bottles accelerated the detection of infectious agents, especially S. aureus, Streptococcus pneumoniae, and C. glabrata. CONCLUSIONS: It is possible to enhance recovery from antibiotic-containing pediatric bottles and shorten TTD for the identification of pathogens by using the BacT/Alert blood culture system combination with new resin-containing media.

Cholangitis with bacteremia due to Pseudomonas nitroreducens in a patient with pancreatic neuroendocrine tumors: a case report.

BACKGROUND: Pseudomonas nitroreducens is a non-fermenting, gram-negative, rod-shaped bacterium commonly inhabiting soil, particularly soil contaminated with oil brine. To our knowledge, no cases of human infection with P. nitroreducens have been previously reported. Here, we present the first documented case of cholangitis caused by P. nitroreducens in a patient with bacteremia. CASE PRESENTATION: A 46-year-old Japanese man with an advanced pancreatic neuroendocrine tumor was hospitalized with fever and chills. Four days before admission, the patient developed right upper abdominal pain. Two days later, he also experienced fever and chills. Endoscopic retrograde cholangiopancreatography was performed on the day of admission, and the patient was diagnosed as having cholangitis associated with stent dysfunction. Gram-negative rods were isolated from blood cultures, but attempts to identify the bacteria using VITEK2 and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) with VITEK MS ver. 4.7.1 (bioMérieux Japan Co. Ltd., Tokyo, Japan) were unsuccessful. Finally, the organism was identified as P. nitroreducens using MALDI-TOF MS with a MALDI Biotyper (Bruker Daltonics Co., Ltd., Billerica, MA, USA) and 16 S ribosomal RNA sequencing. Despite thorough interviews with the patient, he denied any exposure to contaminated soil. The patient was treated with intravenous cefepime and oral ciprofloxacin for 16 days based on susceptibility results, achieving a good therapeutic outcome. At the outpatient follow-up on day 28, the patient was in good general condition. CONCLUSIONS: This is the first reported human case of cholangitis with bloodstream infection caused by P. nitroreducens. This report provides clinicians with novel insights into the clinical manifestations and diagnostic methods necessary for the accurate diagnosis of P. nitroreducens, along with guidance on treatment.

Universal Digital High-Resolution Melt Analysis for the Diagnosis of Bacteremia.

Fast and accurate diagnosis of bloodstream infection is necessary to inform treatment decisions for septic patients, who face hourly increases in mortality risk. Blood culture remains the gold standard test but typically requires approximately 15 hours to detect the presence of a pathogen. We, therefore, assessed the potential for universal digital high-resolution melt (U-dHRM) analysis to accomplish faster broad-based bacterial detection, load quantification, and species-level identification directly from whole blood. Analytical validation studies demonstrated strong agreement between U-dHRM load measurement and quantitative blood culture, indicating that U-dHRM detection is highly specific to intact organisms. In a pilot clinical study of 17 whole blood samples from pediatric patients undergoing simultaneous blood culture testing, U-dHRM achieved 100% concordance when compared with blood culture and 88% concordance when compared with clinical adjudication. Moreover, U-dHRM identified the causative pathogen to the species level in all cases where the organism was represented in the melt curve database. These results were achieved with a 1-mL sample input and sample-to-answer time of 6 hours. Overall, this pilot study suggests that U-dHRM may be a promising method to address the challenges of quickly and accurately diagnosing a bloodstream infection.

Central venous catheter-related bloodstream infections: Epidemiology and risk factors for hematogenous complications.

BACKGROUND: Central catheter-related bloodstream infections (CRBIs) can lead to severe complications, including suppurative thrombophlebitis, endocarditis, and metastatic infections. While complications due to CRBIs caused by Staphylococcus aureus (SA) are well-known, there are limited data regarding CRBIs caused by other bacteria. METHODS: This 2-year retrospective single-center study of patients with CRBIs from a tertiary care hospital examined the hematogenous complications associated with CRBIs according to patient characteristics, central venous catheter (CVC) types, and causative bacteria. RESULTS: All in all, 254 patients with confirmed CRBIs were included; 285 bacteria types were isolated, mainly Enterobacteriaceae (n = 94), coagulase-negative Staphylococci (CNS, n = 82), SA (n = 45), and non-fermenting Gram-negative bacteria (NGB, n = 45). Among the patients, 35 developed at least one hematogenous complication (14 %), including suppurative thrombophlebitis (n = 15), endocarditis (n = 7) and metastatic infections (n = 16). In multivariate analysis, hemodialysis, persistent bacteremia for at least 3 days, and CRBIs caused by SA were associated with increased risk for hematogenous complications, while previous curative anticoagulant treatment was associated with reduced risk. Diabetes, CVC maintenance, and hematogenous complications were associated with increased 3-month mortality. CONCLUSION: A thorough investigation of hematogenous complications should be envisioned in patients with persistent bacteremia, particularly those with SA infections and those on hemodialysis.

Bacterial isolates from positive paired venous catheter and peripheral blood cultures taken during parenteral nutrition were the same species but different strains: A case report.

OBJECTIVE: The same microbial species isolated from blood simultaneously drawn from a central venous catheter hub and a peripheral vein (paired blood cultures) during parenteral nutrition may be assumed to represent the same strain. This case report provides an example of this assumption being incorrect along with a comparator example of it being correct. This has implications for interpretation of differential time to positivity and differential quantitative blood cultures during investigation of suspected intraluminal intravascular catheter or cannula bloodstream infection. CASE DESCRIPTION: Two patients ages ≥18 y prescribed parenteral nutrition each had positive paired blood cultures that had been taken for suspected catheter bloodstream infection because of temperature spikes ≥38°C. The paired Staphylococcus epidermidis isolates from the first patient and the paired Enterococcus faecium isolates from the second patient were each tested beyond routine clinical care to establish if they could be different strains. The central and peripheral isolates of Staphylococcus epidermidis from the first patient were different strains based on hospital-reported antibiograms, genomic DNA profiles, thermograms, and weaker growth and different sizes of colonies of the central strain compared with the peripheral strain. There were no such differences for the isolates of Enterococcus faecium from the second patient. RESULTS: The central and peripheral isolates of Staphylococcus epidermidis from the first patient were different strains based on hospital-reported antibiograms, genomic DNA profiles, thermograms, and weaker growth and different sizes of colonies of the central strain compared with the peripheral strain. There were no such differences for the isolates of Enterococcus faecium from the second patient. CONCLUSION: This case report indicates consideration should be given to reporting whether bacteria have been identified at either species or strain level if differential time to positivity or differential quantitative blood cultures are used to define catheter or cannula bloodstream infection.