Kidney Transplantation From Deceased Donors With Bloodstream Infection: A Multicenter Retrospective Study.

BACKGROUND: The use of organs from donors with infection is limited because of the possibility of transmission. We aimed to investigate the transmission after deceased donor transplantation with bloodstream infection (BSI). METHODS: A retrospective study of patients undergoing kidney or pancreas transplantation at five tertiary centers in Korea from January 2009 and November 2019 was performed. We analyzed the outcomes after transplantation from deceased donors with BSI. RESULTS: Eighty-six recipients received transplantation from 69 donors with BSI. The most common isolated pathogens from donors were Gram-positive bacteria (72.0%), followed by Gram-negative bacteria (22.7%), and fungi (5.3%). Appropriate antimicrobial agents were used in 47.8% of donors before transplantation. Transmission occurred only in 1 of 83 recipients (1.2%) from bacteremic donors and 1 of 6 recipients (16.7%) from fungemic donors. One-year patient and graft survival was 97.5%and 96.3%, respectively. There was no significant difference in graft and patient survival between patients who received organs from infected donors and noninfected donors. CONCLUSION: Using organs from donors with bacteremia seems to be a safe option with low transmission risk. The overall prognosis of using organs from donors with BSI is favorable.

Hypervirulent Streptococcus agalactiae septicemia in twin ex-premature infants transmitted by breast milk: report of source detection and isolate characterization using commonly available molecular diagnostic methods.

BACKGROUND: Group B Streptococcus (GBS) infections caused by Streptococcus agalactiae is a leading cause of meningitis and sepsis in neonates, with early-onset GBS symptoms emerging during the first week of life and late-onset occurring thereafter. Perinatal transmission of GBS to the neonate through the birth canal is the main factor associated with early-onset neonate infections, while less is understood about the source of late-onset infections. METHODS: In this report we describe a case of twin ex-premature infants who presented one month after birth with GBS septicemia. The mother had been appropriately screened at gestational age 35-37 weeks and laboratory methods failed to detect GBS colonization by culture or clinical molecular methods. In attempts to identify and isolate the source of GBS infection, additional surveillance swabs were collected from the mother at the time of neonate admission. Culture and a commercially available, FDA-cleared molecular PCR assay were performed. RESULTS: No GBS was detected from swabs collected from the perianal, thigh/groin or axillary areas. However, expressed breast milk and swabs from the breastmilk pump were positive by both methods. Since simultaneous culture and molecular methods which used breastmilk as a source were performed, investigators ascertained the limit of detection for GBS in breastmilk. The limit of detection was determined to be tenfold lower than that of LIM-broth enriched cultures-the FDA-approved source. Subsequent whole genome sequencing (WGS) analysis of isolates recovered from breastmilk and blood cultures from the infants demonstrated all strains were related and characterized as ST-452. Both infants responded very well to treatment and continued to have no related events or concerns at the two-year follow up appointment. CONCLUSIONS: Strain type 452 (capsular type IV) has recently emerged as a hypervirulent strain and has previously been documented as causing GBS infections in elderly populations. Antibiotic therapy resolved both mother and infant infections. Subsequent testing for the presence of GBS in breastmilk samples also showed an absence of bacteria. This is the first report of infant twins late-onset GBS infections caused by the hypervirulent S. agalactiae ST-452 with breastmilk as the source.

Federal and State Action Needed to End the Infectious Complications of Illicit Drug Use in the United States: IDSA and HIVMA's Advocacy Agenda.

In response to the opioid crisis, IDSA and HIVMA established a working group to drive an evidence- and human rights-based response to illicit drug use and associated infectious diseases. Infectious diseases and HIV physicians have an opportunity to intervene, addressing both conditions. IDSA and HIVMA have developed a policy agenda highlighting evidence-based practices that need further dissemination. This paper reviews (1) programs most relevant to infectious diseases in the 2018 SUPPORT Act; (2) opportunities offered by the "End the HIV Epidemic" initiative; and (3) policy changes necessary to affect the trajectory of the opioid epidemic and associated infections. Issues addressed include leveraging harm reduction tools and improving integrated prevention and treatment services for the infectious diseases and substance use disorder care continuum. By strengthening collaborations between infectious diseases and addiction specialists, including increasing training in substance use disorder treatment among infectious diseases and addiction specialists, we can decrease morbidity and mortality associated with these overlapping epidemics.

Bacteremia with Staphylococcus pseudintermedius in a 4 month old pediatric oncology patient.

Staphylococcus pseudintermedius colonizes and is a pathogen of dogs and is being increasingly recognized from specimens from humans with various infections. We describe a case of S. pseudintermedius bacteremia in a 4 month old pediatric oncology patient with clear evidence of transmission from the family pet.

Whole-Genome Analysis of Livestock-Associated Methicillin-Resistant Staphylococcus aureus Sequence Type 398 Strains Isolated From Patients With Bacteremia in China.

Sequence type (ST) 398 is the most prevalent clone of livestock-associated methicillin-resistant Staphylococcus aureus (MRSA). To evaluate the molecular characteristics and phylogeny of Chinese ST398 isolates, 4 MRSA ST398 strains and 4 methicillin-susceptible S. aureus (MSSA) ST398 strains were collected from patients with bacteremia at 6 teaching hospitals in China between 1999 and 2016. Moreover, 689 ST398 genome sequences were downloaded from the GenBank database for comparison. The 4 MRSA ST398 strains were resistant to ß-lactam antibiotics, and 2 strains were also resistant to erythromycin. Among the 4 MSSA ST398 strains, 2 strains displayed multidrug resistance (MDR) and were resistant to penicillin, erythromycin, tetracycline, and gentamicin. The accessory genome of MSSA ST398 was more diverse than that of MRSA ST398. All 4 MRSA ST398 strains carried type V staphylococcal cassette chromosome mec elements; however, MSSA ST398 carried more resistance genes than MRSA ST398. These 4 MRSA ST398 strains carried hemolysin, along with virulence genes associated with immune invasion and protease. Phylogenic analysis showed that the 4 MRSA ST398 strains clustered in 1 clade. The global ST398 phylogeny showed that ST398 was divided into an animal clade and a human clade, and the ST398 strains of this study clustered in the human clade. A small number of human strains were also present in the animal clade and vice versa, suggesting transmission of ST398 between animals and humans. In conclusion, livestock-associated MRSA ST398 has caused severe infections in Chinese hospitals, and it should therefore be paid more attention to and monitored.

Whole-genome sequencing to explore nosocomial transmission and virulence in neonatal methicillin-susceptible Staphylococcus aureus bacteremia.

BACKGROUND: Neonatal Staphylococcus aureus (S. aureus) bacteremia is an important cause of morbidity and mortality. In this study, we examined whether methicillin-susceptible S. aureus (MSSA) transmission and genetic makeup contribute to the occurrence of neonatal S. aureus bacteremia. METHODS: A retrospective, single-centre study was performed. All patients were included who suffered from S. aureus bacteremia in the neonatal intensive care unit (NICU), Erasmus MC-Sophia, Rotterdam, the Netherlands, between January 2011 and November 2017. Whole-genome sequencing (WGS) was used to characterize the S. aureus isolates, as was also done in comparison to reference genomes. Transmission was considered likely in case of genetically indistinguishable S. aureus isolates. RESULTS: Excluding coagulase-negative staphylococci (CoNS), S. aureus was the most common cause of neonatal bacteremia. Twelve percent (n = 112) of all 926 positive blood cultures from neonates grew S. aureus. Based on core genome multilocus sequence typing (cgMLST), 12 clusters of genetically indistinguishable MSSA isolates were found, containing 33 isolates in total (2-4 isolates per cluster). In seven of these clusters, at least two of the identified MSSA isolates were collected within a time period of one month. Six virulence genes were present in 98-100% of all MSSA isolates. In comparison to S. aureus reference genomes, toxin genes encoding staphylococcal enterotoxin A (sea) and toxic shock syndrome toxin 1 (tsst-1) were present more often in the genomes of bacteremia isolates. CONCLUSION: Transmission of MSSA is a contributing factor to the occurrence of S. aureus bacteremia in neonates. Sea and tsst-1 might play a role in neonatal S. aureus bacteremia.

Systemic infection facilitates transmission of Pseudomonas aeruginosa in mice.

Health care-associated infections such as Pseudomonas aeruginosa bacteremia pose a major clinical risk for hospitalized patients. However, these systemic infections are presumed to be a "dead-end" for P. aeruginosa and to have no impact on transmission. Here, we use a mouse infection model to show that P. aeruginosa can spread from the bloodstream to the gallbladder, where it replicates to extremely high numbers. Bacteria in the gallbladder can then seed the intestines and feces, leading to transmission to uninfected cage-mate mice. Our work shows that the gallbladder is crucial for spread of P. aeruginosa from the bloodstream to the feces during bacteremia, a process that promotes transmission in this experimental system. Further research is needed to test to what extent these findings are relevant to infections in patients.

A Complete Genome Screening Program of Clinical Methicillin-Resistant Staphylococcus aureus Isolates Identifies the Origin and Progression of a Neonatal Intensive Care Unit Outbreak.

Whole-genome sequencing (WGS) of Staphylococcus aureus is increasingly used as part of infection prevention practices. In this study, we established a long-read technology-based WGS screening program of all first-episode methicillin-resistant Staphylococcus aureus (MRSA) blood infections at a major urban hospital. A survey of 132 MRSA genomes assembled from long reads enabled detailed characterization of an outbreak lasting several months of a CC5/ST105/USA100 clone among 18 infants in a neonatal intensive care unit (NICU). Available hospital-wide genome surveillance data traced the origins of the outbreak to three patients admitted to adult wards during a 4-month period preceding the NICU outbreak. The pattern of changes among complete outbreak genomes provided full spatiotemporal resolution of its progression, which was characterized by multiple subtransmissions and likely precipitated by equipment sharing between adults and infants. Compared to other hospital strains, the outbreak strain carried distinct mutations and accessory genetic elements that impacted genes with roles in metabolism, resistance, and persistence. This included a DNA recognition domain recombination in the hsdS gene of a type I restriction modification system that altered DNA methylation. Transcriptome sequencing (RNA-Seq) profiling showed that the (epi)genetic changes in the outbreak clone attenuated agr gene expression and upregulated genes involved in stress response and biofilm formation. Overall, our findings demonstrate the utility of long-read sequencing for hospital surveillance and for characterizing accessory genomic elements that may impact MRSA virulence and persistence.

Characterization of ESBL-Producing Salmonella enterica Serovar Infantis Infection in Humans, Lima, Peru.

Salmonella enterica serovar Infantis is causing an increasing number of infections worldwide. Our aim was to describe the characteristics of S. enterica serovar Infantis among patients attended in a hospital of Lima, Peru. Fifty cases of salmonellosis were seen during October 2015-May 2017; Salmonella Infantis was detected in 36% (n = 18) of them, displacing Enteritidis and Typhimurium (n = 13, 26%, each). Seventeen cases caused by Salmonella Infantis were presented as diarrheal illnesses; only one extraintestinal case (bacteremia) was seen in a 1-year-old infant. This serovar is resistant to multiple groups of antimicrobials, showing only fully susceptibility to carbapenems. Compared with Infantis, other serovars analyzed (mainly Enteritidis and Typhimurium) showed a lower frequency of resistance to antimicrobials such as trimethoprim-sulfamethoxazole, ampicillin, and chloramphenicol. The antibiotic with the highest frequency of resistance was ciprofloxacin. Further studies are needed to evaluate the routes of transmission and measures of control of this multidrug-resistant Salmonella.

Incidence and Risk Factors for Systemic Infection in Deceased Donors.

BACKGROUND: Organ donation shortage is the primary barrier to all organ transplantations.Infectious disease transmission through transplantation is considered controversial for organ retrieval. Donors with bacteremia and sepsis are considered controversial for organ retrieval due to potential transmission of an infectious agent to the recipient. METHODS: We retrospectively reviewed the results of bacterial culture of the donor's blood from peripheral venous or central venous catheter, urine, and bronchial aspiration from the organ donation registries of 102 potential donors from the Ministry of Health and Tissue Transplant Coordination Center of Istanbul Region in 2015. RESULTS: Of the 102 deceased donors included in the analysis, 24 (23.5%) had infection. The most common sites of infection were the bloodstream (41.6%) and the respiratory system (37.5%). The most common isolated pathogens of the bacterial cultures were Gram-positive bacteria (21), Gram-negative microorganisms (14), and Candida (1). The significant risk factor for infection was duration of stay at the intensive care unit (median: 5 day; 25-75%: 3-5 day) (odds ratio, 2.94; 95% confidence interval, 1.06-8.12; P < .05). The presence of infection in the donor accounted for a significant part of the reasons why the organs were not accepted for transplantation (kidneys 9%, liver 4%, heart 6%). CONCLUSIONS: The study showed that deceased donors with prolonged stays in the intensive care unit have an increased risk for developing nosocomial infections; so there is a need for establishing and enforcing the prevention and control of infection in possible donors.

Impact of single-room contact precautions on hospital-acquisition and transmission of multidrug-resistant Escherichia coli: a prospective multicentre cohort study in haematological and oncological wards.

OBJECTIVES: Colonization and infection with third-generation cephalosporin-resistant Escherichia coli (3GCR-EC) are frequent in haematological and oncological patients. In this high-risk setting, German guidelines recommend single-room contact precautions (SCP) for patients with 3GCR-EC that are non-susceptible to fluoroquinolones (F3GCR-EC). However, this recommendation is controversial, as evidence is limited. METHODS: We performed a prospective, multicentre cohort study at four haematology and oncology departments assessing the impact of SCP on hospital-acquired colonization or bloodstream infection (BSI) with F3GCR-EC. Two sites performed SCP for F3GCR-EC patients including single rooms, gloves and gowns (SCP sites), and two did not (NCP sites). Active screening for 3GCR-EC was performed and isolates were characterized with molecular typing methods including whole genome sequencing and core genome multiple locus sequence typing to assess patient-to-patient transmission. Potential confounders were assessed by competing-risk regression analysis. RESULTS: Within 12 months, 1386 patients at NCP sites and 1582 patients at SCP sites were included. Hospital-acquisition of F3GCR-EC was observed in 22/1386 (1.59%) and 16/1582 (1.01%) patients, respectively (p 0.191). There were 3/1386 (0.22%) patients with BSI caused by F3GCR-EC at NCP sites and 4/1582 (0.25%) at SCP sites (p 1.000). Patient-to-patient transmission occurred in three cases at NCP and SCP sites each (p 1.000). The number of patients needed to screen in order to prevent one patient-to-patient transmission of F3GCR-EC was determined to be 3729. CONCLUSIONS: Use of SCP had no significant impact on hospital-acquisition or patient-to-patient transmission of F3GCR-EC in this high-risk setting.

Neonatal meningitis and recurrent bacteremia with group B Streptococcus transmitted by own mother's milk: A case report and review of previous cases.

This article reports a case of neonatal meningitis and recurrent bacteremia caused by group B Streptococcus (GBS) transmitted via the mother's milk. A 3-day-old neonate suffered early-onset meningitis due to GBS, from which he recovered after antibiotic treatment for 4 weeks. GBS was not detected in the vaginal or stool cultures of the neonate's mother before delivery. However, 4days after treatment of GBS meningitis, the neonate developed GBS bacteremia. As the mother repeatedly showed signs of mastitis after the delivery, bacterial culture tests were performed on her breast milk, in addition to vaginal and stool culture tests. GBS was exclusively detected in the mother's breast milk. The GBS strains detected in the cerebrospinal fluid of the neonate and the mother's breast milk were both serotype III, and were confirmed to be identical through pulsed-field gel electrophoresis analysis. As horizontal GBS transmission between the mother and neonate was indicated, breastfeeding was ceased and replaced with formula milk. No recurrence of bacterial meningitis or bacteremia due to GBS was observed thereafter. Physicians need to consider culturing breast milk in cases of recurrent neonatal GBS infections, even in mothers without prior detection of GBS in conventional vaginal or stool cultures before delivery.

Long-term Staphylococcus aureus decolonization in patients on home parenteral nutrition: study protocol for a randomized multicenter trial.

BACKGROUND: Patients with long-term intestinal failure are usually treated by means of home parenteral nutrition (HPN) where they administer their nutritional formulation intravenously via a central venous access device (mostly a catheter). This implies that such patients are exposed to a lifelong risk of developing Staphylococcus aureus bacteremia (SAB). SAB poses a threat to both catheter and patient survival and may lead to frequent hospitalization and a permanent loss of vascular access. In other clinical settings, S. aureus carriage eradication has been proven effective in the prevention of S. aureus infections. Unfortunately, there is a complete lack of evidence in HPN support on the most effective and safe S. aureus decolonization strategy in S. aureus carriers. We hypothesized that long-term S. aureus decolonization in HPN patients can only be effective if it is aimed at the whole body (nasal and extra-nasal) and is given chronically or repeatedly on indication. Besides this, we believe that S. aureus carriage among caregivers, who are in close contact with the patient, are of great importance in the S. aureus transmission routes. METHODS/DESIGN: The CARRIER trial is a randomized, open-label, multicenter clinical trial in Dutch and Danish hospitals that treat patients on HPN. A total of 138 adult HPN patients carrying S. aureus will be randomly assigned to a search and destroy (SD) strategy, a quick and short, systemic antibiotic treatment, or a continuous suppression (CS) strategy, a repeated chronic topical antibiotic treatment. The primary outcome measure is the proportion of patients in whom S. aureus is totally eradicated during a 1-year period. Secondary outcomes are time to successful eradication, long-term antimicrobial resistance, adverse events, patient compliance, incidence of (S. aureus) infections, catheter removals, mortality rates, S. aureus transmission routes, quality of life, and health care costs. DISCUSSION: The CARRIER trial is designed to identify the most safe and effective long-term S. aureus carriage decolonization strategy in HPN patients. This will eventually lead to a better understanding of long-term S. aureus decolonization treatments in general. The results of this study will have a great impact on our daily clinical practice, which eventually may result in less S. aureus-related infections. TRIAL REGISTRATION: ClinicalTrials.gov; NCT03173053 . Registered on 1 June 2017.

Nosocomial transmission of carbapenem-resistant Klebsiella pneumoniae in an Italian university hospital: a molecular epidemiological study.

AIM: To describe the phenotypic and genotypic profiles of Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-Kp) strains isolated from patients with invasive infections at an Italian university hospital in order to assess the epidemiological trend. METHODS: An observational prospective study was undertaken at the University Hospital of Sassari, Italy to detect KPC-Kp strains in patients with invasive bacteraemia. Isolates were identified phenotypically; carbapenemase production was assessed using phenotypic and genotypic methods. Sequencing of blaKPC genes, pulsed-field gel electrophoresis and multi-locus sequence typing were performed. RESULTS: During the period 2015-2017, 46 cases of invasive infection with K. pneumoniae were recorded. Two-thirds (67.4%) of the patients were male, and the mean age was 69.4 years. Most patients had at least one comorbidity (56.5%) and/or had been hospitalized previously (70.5%), 81.8% had current or recent medical device use, and 85.4% had recent antibiotic exposure. The mortality rate was 52.3%. A multi-drug-resistant pattern (including carbapenems, fluoroquinolones, third-/fourth-generation cephalosporins) was shown for all K. pneumoniae isolates. KPC-3 and -2 were produced by all strains. The most common sequence types were 512 (91.3%) and 101 (8.7%), grouped into three clusters (A, A1 and B). CONCLUSIONS: A high incidence of KPC-Kp in patients with invasive infections was recorded at an Italian university hospital compared with the incidence measured before 2015. This study confirmed the importance of the KPC-3 carbapenemase variant, as reported by other Italian studies. High mortality and comorbidity rates appear to be associated with KPC-Kp infection.

Red blood cells treated with the amustaline (S-303) pathogen reduction system: a transfusion study in cardiac surgery.

BACKGROUND: Nucleic acid-targeted pathogen inactivation technology using amustaline (S-303) and glutathione (GSH) was developed to reduce the risk of transfusion-transmitted infectious disease and transfusion-associated graft-versus-host disease with red blood cell (RBC) transfusion. STUDY DESIGN AND METHODS: A randomized, double-blind, controlled study was performed to assess the in vitro characteristics of amustaline-treated RBCs (test) compared with conventional (control) RBCs and to evaluate safety and efficacy of transfusion during and after cardiac surgery. The primary device efficacy endpoint was the postproduction hemoglobin (Hb) content of RBCs. Exploratory clinical outcomes included renal and hepatic failure, the 6-minute walk test (a surrogate for cardiopulmonary function), adverse events (AEs), and the immune response to amustaline-treated RBCs. RESULTS: A total of 774 RBC unis were produced. Mean treatment difference in Hb content was -2.27 g/unit (95% confidence interval, -2.61 to -1.92 g/unit), within the prespecified equivalence margins (±5 g/unit) to declare noninferiority. Amustaline-treated RBCs met European guidelines for Hb content, hematocrit, and hemolysis. Fifty-one (25 test and 26 control) patients received study RBCs. There were no significant differences in RBC usage or other clinical outcomes. Observed AEs were within the spectrum expected for patients of similar age undergoing cardiovascular surgery requiring RBCs transfusion. No patients exhibited an immune response specific to amustaline-treated RBCs. CONCLUSION: Amustaline-treated RBCs demonstrated equivalence to control RBCs for Hb content, have appropriate characteristics for transfusion, and were well tolerated when transfused in support of acute anemia. Renal impairment was characterized as a potential efficacy endpoint for pivotal studies of RBC transfusion in cardiac surgery.

Storage time of platelet concentrates and risk of a positive blood culture: a nationwide cohort study.

BACKGROUND: Concern of transfusion-transmitted bacterial infections has been the major hurdle to extend shelf life of platelet (PLT) concentrates. We aimed to investigate the association between storage time and risk of positive blood cultures at different times after transfusion. STUDY DESIGN AND METHODS: We performed a nationwide cohort study among PLT transfusion recipients in Denmark between 2010 and 2012, as recorded in the Scandinavian Donations and Transfusions (SCANDAT2) database. Linking with a nationwide database on blood cultures (MiBa), we compared the incidence of a positive blood culture among recipients of PLTs stored 6 to 7 days (old) to those receiving fresh PLTs (1-5 days), using Poisson regression models. We considered cumulative exposures in windows of 1, 3, 5, and 7 days. RESULTS: A total of 9776 patients received 66,101 PLT transfusions. The incidence rate ratio (IRR) of a positive blood culture the day after transfusion of at least one old PLT concentrate was 0.77 (95% confidence interval [CI], 0.54-1.09) compared to transfusion of fresh PLT concentrates. The incidence rate of a positive blood culture was lower the day after receiving one old compared to one fresh PLT concentrate (IRR, 0.57; 95% CI, 0.37-0.87). Three, 5, or 7 days after transfusion, storage time was not associated with the risk of a positive blood culture. CONCLUSION: Storage of buffy coat-derived PLT concentrates in PAS-C up to 7 days seems safe regarding the risk of a positive blood culture. If anything, transfusion of a single old PLT concentrate may decrease this risk the following day.

Investigation of a Cluster of Sequence Type 22 Methicillin-Resistant Staphylococcus aureus Transmission in a Community Setting.

BACKGROUND: Whole-genome sequencing (WGS) has typically been used to confirm or refute hospital/ward outbreaks of methicillin-resistant Staphylococcus aureus (MRSA) identified through routine practice. However, appropriately targeted WGS strategies that identify routinely "undetectable" transmission remain the ultimate aim. METHODS: WGS of MRSA isolates sent to a regional microbiological laboratory was performed as part of a 12-month prospective observational study. Phylogenetic analyses identified a genetically related cluster of E-MRSA15 isolated from patients registered to the same general practice (GP) surgery. This led to an investigation to identify epidemiological links, find additional cases, and determine potential for ongoing transmission. RESULTS: We identified 15 MRSA-positive individuals with 27 highly related MRSA isolates who were linked to the GP surgery, 2 of whom died with MRSA bacteremia. Of the 13 cases that were further investigated, 11 had attended a leg ulcer/podiatry clinic. Cases lacked epidemiological links to hospitals, suggesting that transmission occurred elsewhere. Environmental and staff screening at the GP surgery did not identify an ongoing source of infection. CONCLUSIONS: Surveillance in the United Kingdom shows that the proportion of MRSA bacteremias apportioned to hospitals is decreasing, suggesting the need for greater focus on the detection of MRSA outbreaks and transmission in the community. This case study confirms that the typically nosocomial lineage (E-MRSA15) can transmit within community settings. Our study exemplifies the continued importance of WGS in detecting outbreaks, including those which may be missed by routine practice, and suggests that universal WGS of bacteremia isolates may help detect outbreaks in low-surveillance settings.