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.

Stepwise evolution of Salmonella Typhimurium ST313 causing bloodstream infection in Africa.

Bloodstream infections caused by nontyphoidal Salmonella are a major public health concern in Africa, causing ~49,600 deaths every year. The most common Salmonella enterica pathovariant associated with invasive nontyphoidal Salmonella disease is Salmonella Typhimurium sequence type (ST)313. It has been proposed that antimicrobial resistance and genome degradation has contributed to the success of ST313 lineages in Africa, but the evolutionary trajectory of such changes was unclear. Here, to define the evolutionary dynamics of ST313, we sub-sampled from two comprehensive collections of Salmonella isolates from African patients with bloodstream infections, spanning 1966 to 2018. The resulting 680 genome sequences led to the discovery of a pan-susceptible ST313 lineage (ST313 L3), which emerged in Malawi in 2016 and is closely related to ST313 variants that cause gastrointestinal disease in the United Kingdom and Brazil. Genomic analysis revealed degradation events in important virulence genes in ST313 L3, which had not occurred in other ST313 lineages. Despite arising only recently in the clinic, ST313 L3 is a phylogenetic intermediate between ST313 L1 and L2, with a characteristic accessory genome. Our in-depth genotypic and phenotypic characterization identifies the crucial loss-of-function genetic events that occurred during the stepwise evolution of invasive S. Typhimurium across Africa.

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.

Pseudomonas poae-Associated Fatal Septic Transfusion Reaction, Peoria, Illinois, USA, 2017.

In the United States, fatal transfusion-transmitted infections from red blood cell units are rare. Although this pattern mostly reflects how inhospitable refrigerated red blood cell units are to contaminant growth, fatalities caused by microorganisms that can grow at storage temperature (4°C), but not in standard clinical blood cultures at 37°C, are probably underestimated. We analyzed a fatal red blood cell transfusion in Peoria, Illinois, USA, that occurred in 2017. Samples from the patient's whole blood and the red blood cell unit remained culture-negative during the investigation, despite direct visualization of gram-negative bacilli within the unit immediately after transfusion. We identified the bacteria as Pseudomonas poae, a nonpathogenic pseudomonad carrying multiple cold-shock domain protein genes, and confirmed its cold tolerance and inability to grow at 37°C. Our work indicates transfusion reaction workups need to include testing for psychrophilic organisms, which could explain the cause of other apparently culture-negative transfusion reactions.

Staphylococcus capitis and NRCS-A clone: the story of an unrecognized pathogen in neonatal intensive care units.

BACKGROUND: In neonatal intensive care units (NICUs), nosocomial late-onset sepsis (LOS), mostly due to coagulase negative staphylococci, constitute a major cause of death or impairment. Staphylococcus capitis, usually considered as a poorly virulent species, has been reported as a cause of LOS. OBJECTIVES: To review data regarding S. capitis neonatal LOS and the features of isolates involved. SOURCES: PubMed was searched up to August 2018 to retrieve studies on the topic; the keywords used were 'S. capitis', 'neonate', 'neonatal ICU', 'bloodstream infection' and 'late onset sepsis'. CONTENT: Published data highlight the worldwide endemicity of a single S. capitis clone, named NRCS-A, specifically involved in LOS. NRCS-A harbours a multidrug resistance profile (including resistance to the usual first-line antibiotics used in NICUs). It is also able to adapt under vancomycin selective pressure that could confer an advantage for its implantation and dissemination in NICUs where this selective pressure is high. Moreover, a severe morbidity has been observed in NRCS-A-related LOS. The NICU environment, and especially incubators, constitute reservoirs of NRCS-A from which it could diffuse inside the setting. Finally, the virulome and resistome of S. capitis NRCS-A contain many genes potentially implicated in its specific epidemiology and pathophysiology, including the gene nsr that may be involved in its fitness and implantation in neonatal gut flora. IMPLICATIONS: S. capitis must be considered as a true pathogen in neonates. The decreased susceptibility to vancomycin may be involved in failure of vancomycin therapy. Further studies are needed to better manage its diffusion inside each NICU but also worldwide.

Risk of subsequent health care-associated infection among patients with a bloodstream infection present on hospital admission.

BACKGROUND: The risks and outcomes of acquiring a health care-associated infection (HAI) among patients with a bloodstream infection present on hospital admission (BSI-POA) have not been well described. The objective of this study was to examine the incidence of and risk factors for developing a subsequent HAI and to compare length of stay and mortality between patients with a BSI-POA who develop an HAI and those who do not. METHODS: This was a retrospective cohort study of patients aged ≥18 years discharged with a BSI-POA from 3 hospitals in New York City between 2006 and 2014. RESULTS: There were 761 HAIs among the 11,436 patients with a BSI-POA. Incidence rates were: catheter-associated urinary tract infections, 5.03 infections per 1,000 catheter days; pneumonia, 2.7% among BSI-POA patients; surgical site infections, 9.2% among BSI-POA patients. Length of stay was longer among patients who developed an HAI (mean ± SD, 35.0 ± 29.8 vs 12.4 ± 11.9, P < .001). Mortality was higher in patients who developed an HAI (23.9% vs 11.6%, P < .001). CONCLUSIONS: Risk factors for those who developed an HAI differed by infection type. Overall, HAI was associated with longer hospitalization, and pneumonia was associated with increased mortality.

Staphylococcus pseudintermedius septicemia in puppies after elective cesarean section: confirmed transmission via dam's milk.

BACKGROUND: In humans, transmission of bacteria causing fatal sepsis in the neonates through mother's milk has been reported. In dogs, it is believed that bacteria from canine milk are not the primary cause of neonatal infections. Staphylococcus pseudintermedius is colonizing the skin and mucocutaneous junctions in adult dogs and can act as an opportunistic pathogen. This bacterium was previously isolated from the canine milk and, although, its transmission from the dam's milk to the newborn puppies causing a neonatal sepsis was suggested, this hypothesis has not been confirmed. CASE PRESENTATION: A 4.5-year-old healthy Boston terrier dam had an elective cesarean section, delivering five normal puppies and one dead runt. Next day, two puppies developed pustules on their legs and around the muzzle. After two more days, strings of blood were noticed in the stool of the biggest puppy that suddenly died later that night. The same day, blood became visible in the feces of all other puppies. Necropsy of the dead puppy revealed a distended abdomen, catarrhal gastroenteritis with lymphadenopathy, dark red and slightly firm lung, mild dilatation of the right heart chamber and congestion of the liver, spleen, pancreas and meninges. The thoracic cavity contained white-yellow slightly opaque exudate, and there was transudate in the abdominal cavity. Histopathology revealed an acute interstitial pneumonia and multifocal myocardial necrosis with mineralization. Bacteriology of the internal organs, body cavity effusions of the dead puppy and dam's milk revealed a diffuse growth of S. pseudintermedius in pure culture. Whole genome sequencing (WGS) revealed that all isolates belonged to the sequence type 241 and differed in 2-5 single nucleotide polymorphisms; thus, the epidemiological link between the outbreak-associated isolates was confirmed. CONCLUSIONS: This is the first report of a confirmed transmission of S. pseudintermedius through dam's milk causing a neonatal sepsis in a puppy after an elective cesarean section. The epidemiological link between S. pseudintermedius isolates obtained from dam's milk and internal organs of the affected puppy was confirmed by WGS. Our findings indicate that milk of healthy dams can serve as a reservoir of bacteria that can cause fatal sepsis in the newborn puppies.

Intrafamilial Transmission of Parechovirus A and Enteroviruses in Neonates and Young Infants.

BACKGROUND: Parechovirus A (PeV-A) is an important cause of sepsis and meningoencephalitis in neonates and young infants. Thus, identifying the source of PeV-A is essential for prevention; however, little is known regarding the spread of PeV-A among family members of PeV-A-infected neonates and young infants. METHODS: In this prospective study, we evaluated stool samples from family members of PeV-A-infected neonates and infants younger than 4 months who presented with sepsis, meningoencephalitis, or both in Niigata, Japan, in 2016. Because of a simultaneous outbreak, enteroviruses (EVs) were also evaluated during this period. Real-time polymerase chain reaction followed by sequence analysis was used for viral diagnosis using serum and/or cerebrospinal fluid samples. RESULTS: Among 54 febrile patients, the stool samples of 14 (26%) and 12 (22%) patients tested positive for PeV-A and EV, respectively. Stool samples from 54 family members (38 adults and 16 children) of 12 PeV-A-infected patients were available. The rate of PeV-A positivity in these samples was higher among the children (88% [14 of 16]) than the adults (34% [13 of 38]). Among family members with a PeV-A-positive stool sample, 29% (4 of 14) of the children and 77% (10 of 13) of the adults were asymptomatic. Similarly, among 53 stool samples from family members (31 adults and 22 children) of 11 EV-infected patients, the rate of EV positivity in the stool samples was higher among the children (91% [20 of 22]) than among the adults (42% [13 of 31]). The asymptomatic-patient rates were 45% (9 of 20) among the children and 85% (11 of 13) among the adults in family members with EV-positive stool. CONCLUSIONS: Similar to EVs, PeV-A was detected frequently in stool samples from family members of PeV-A-infected patients. Among family members with PeV-A-positive stool, adults were more likely than children to be asymptomatic and therefore could be an important source of PeV-A infection.

Reduction of nosocomial bloodstream infections and nosocomial vancomycin-resistant Enterococcus faecium on an intensive care unit after introduction of antiseptic octenidine-based bathing.

BACKGROUND: Vancomycin-resistant Enterococcus faecium (VRE) is emerging in German intensive care units (ICUs). On a 32-bed surgical ICU at a university hospital, increasing numbers of nosocomial cases occurred despite enforcement of hand hygiene and environmental disinfection. AIM: To introduce universal octenidine-based bathing in order to reduce the burden of VRE. METHODS: Between January 2012 and March 2014, patients were screened for VRE on admission and twice weekly. Active surveillance was undertaken for VRE infections and colonizations, and for bloodstream infections (BSI) with any pathogen. Intervention in this before-after study comprised of standardized octenidine-based bathing. Distinct subgroups of VRE colonizations or infections were defined and used for statistical analysis of frequency, prevalence and incidence density. FINDINGS: In the pre-intervention period (January 2012 to April 2013), the admission prevalence of VRE was 4/100 patients and the mean incidence density of nosocomial cases was 7.55/1000 patient-days (PD). Pulsed-field gel electrophoresis analysis revealed prevalence of three vanA and two vanB clusters. In the post-intervention period (August 2013 to March 2014), the admission prevalence of VRE was 2.41/100 patients and the mean incidence density of nosocomial cases was 2.61/1000 PD [P = 0.001 (pre- vs post-intervention)]. Thirteen nosocomial VRE infections were identified in the pre-intervention period, compared with one nosocomial VRE infection in the post-intervention period. Incidence densities of BSI pre- and post-intervention were 2.98 and 2.06/1000 PD (P = 0.15), respectively. CONCLUSION: The epidemiology of emerging VRE appeared as a complex mix of admitted cases and transmissions in small clusters, challenging infection control measures. The implementation of universal octenidine-based bathing combined with a standardized washing regime led to a significant reduction in nosocomial VRE.

The evolutionary logic of sepsis.

The recently proposed Microbiome Mutiny Hypothesis posits that members of the human microbiome obtain information about the host individuals' health status and, when host survival is compromised, switch to an intensive exploitation strategy to maximize residual transmission. In animals and humans, sepsis is an acute systemic reaction to microbes invading the normally sterile body compartments. When induced by formerly mutualistic or neutral microbes, possibly in response to declining host health, sepsis appears to fit the 'microbiome mutiny' scenario except for its apparent failure to enhance transmission of the causative organisms. We propose that the ability of certain species of the microbiome to induce sepsis is not a fortuitous side effect of within-host replication, but rather it might, in some cases, be the result of their adaptive evolution. Whenever host health declines, inducing sepsis can be adaptive for those members of the healthy human microbiome that are capable of colonizing the future cadaver and spread by cadaver-borne transmission. We hypothesize that such microbes might exhibit switches along the 'mutualist - lethal pathogen - decomposer - mutualist again' scenario, implicating a previously unsuspected, surprising level of phenotypic plasticity. This hypothesis predicts that those species of the healthy microbiome that are recurring causative agents of sepsis can participate in the decomposition of cadavers, and can be transmitted as soil-borne or water-borne infections. Furthermore, in individual sepsis cases, the same microbial clones that dominate the systemic infection that precipitates sepsis, should also be present in high concentration during decomposition following death: this prediction is testable by molecular fingerprinting in experimentally induced animal models. Sepsis is a leading cause of human death worldwide. If further research confirms that some cases of sepsis indeed involve the 'mutiny' (facultative phenotypic switching) of normal members of the microbiome, then new strategies could be devised to prevent or treat sepsis by interfering with this process.

Experimental Sepsis Severity Score Associated to Mortality and Bacterial Spreading is Related to Bacterial Load and Inflammatory Profile of Different Tissues.

Pneumonia-induced sepsis is responsible for about 50% of cases in the world. Patients who develop severe sepsis and septic shock present organ dysfunction and elevated plasma cytokine levels, which may lead to death. Clinical scores are important to evaluate the framework of septic patients and are used to predict the syndrome progress, prognostics, and mortality. The objective of the present study was to verify the applicability of a murine clinical score system to experimental sepsis (pneumonia-induced sepsis in male mice) and to correlate it with mortality and bacterial dissemination in different organs. Results demonstrated that animals which present higher clinical scores (>3) are more likely to die. Animals presenting high clinical scores exhibited transient bacteremia and displayed bacterial spreading to different organs such as heart, kidney, liver, and brain. There is a correlation between clinical score and bacterial dissemination and consequently greater risk of death. In addition, animals which showed bacterial dissemination in more than three organs and high clinical scores presented high levels of cytokines (TNF-α, MCP-1, IL-6, and IL-10) in plasma, lung, heart, liver, kidney, and brain. Therefore, our study suggests that (1) severity scores have predictive power in experimental models of sepsis and (2) high concentrations of tissue cytokines may contribute to localized inflammation and be one of the factors responsible for the systemic inflammatory syndrome of sepsis.

Improved yield of minimal proportional sample volume platelet bacterial culture.

BACKGROUND: Reports of septic transfusion reactions (STRs) after transfusion of culture-negative platelets (PLTs) justify more effective prevention strategies. Pathogen reduction technologies or performance of additional point-of-issue testing are proposed strategies to enhance safety through Day 5 of storage. STUDY DESIGN AND METHODS: Trima leukoreduced apheresis PLTs (APs) were collected during two study periods (45 and 31 months) using standard procedures, with target settings adjusted during the second period to maintain split rate after increased culture volume. Primary testing for bacterial contamination was performed using BacT/ALERT 3D with sampling from the mother bag 24 to 36 hours after collection. Two culture approaches were compared: in Period A, an 8-mL sample in one aerobic culture bottle (CB), and in Period B a minimal proportional sample volume (PSV) of at least 3.8% of mother bag volume into one to three aerobic CBs (7-10 mL per bottle). RESULTS: In Periods A and B, 188,389 and 159,098 AP collections were tested, respectively. The true-positive (TP) rate in Period A was 0.90 per 10,000 collections and in Period B was 1.83 per 10,000 (p < 0.05). In Period B, 12 of 29 (41%) TP results had discrepant CB results (DCBRs; at least one of multiple bottles without growth). The false-positive rate in Period B, 15.05 per 10,000 collections, was significantly higher than that of Period A, 3.66 per 10,000. One contaminated collection resulting in STR(s) was reported in each study period. Implementation of PSV was operationally successful and did not impact the AP split rate. CONCLUSION: Proportional sample volume improved the sensitivity of primary testing and identified collections that could have escaped detection had only a single bottle with 8- to 10-mL volume been used. PSV may represent another approach to enhanced PLT safety for 5-day storage without a requirement for secondary testing.

Towards pathogen inactivation of red blood cells and whole blood targeting viral DNA/RNA: design, technologies, and future prospects for developing countries.

Over 110 million units of blood are collected yearly. The need for blood products is greater in developing countries, but so is the risk of contracting a transfusion-transmitted infection. Without efficient donor screening/viral testing and validated pathogen inactivation technology, the risk of transfusion-transmitted infections correlates with the infection rate of the donor population. The World Health Organization has published guidelines on good manufacturing practices in an effort to ensure a strong global standard of transfusion and blood product safety. Sub-Saharan Africa is a high-risk region for malaria, human immunodeficiency virus (HIV), hepatitis B virus and syphilis. Southeast Asia experiences high rates of hepatitis C virus. Areas with a tropical climate have an increased risk of Zika virus, Dengue virus, West Nile virus and Chikungunya, and impoverished countries face economical limitations which hinder efforts to acquire the most modern pathogen inactivation technology. These systems include Mirasol® Pathogen Reduction Technology, INTERCEPT®, and THERAFLEX®. Their procedures use a chemical and ultraviolet or visible light for pathogen inactivation and significantly decrease the threat of pathogen transmission in plasma and platelets. They are licensed for use in Europe and are used in several other countries. The current interest in the blood industry is the development of pathogen inactivation technologies that can treat whole blood (WB) and red blood cell (RBC). The Mirasol system has recently undergone phase III clinical trials for treating WB in Ghana and has demonstrated some efficacy toward malaria inactivation and low risk of adverse effects. A 2nd-generation of the INTERCEPT® S-303 system for WB is currently undergoing a phase III clinical trial. Both methodologies are applicable for WB and components derived from virally reduced WB or RBC.

Organ Donation and Transplantation From Donors With Systemic Infection: A Single-Center Experience.

OBJECTIVES: Donors with bacteremia and sepsis are often considered to be controversial for organ retrieval due to potential transmission of an infectious agent to the recipient. Herein we report our initial experience of organ donation and transplantation results from donors with systemic infection. MATERIALS AND METHODS: From January 2013 to December 2014, 125 cases of donation were completed in our organ procurement organization including 90 cases of donation after brain death (DBD) and 35 cases of donation after circulatory death (DCD). The results of bacterial culture of the donor's peripheral venous blood (PVB), blood from central venous catheter (BCVC), urine, bronchial aspiration, and tip of central venous catheter (TCVC; Maki's semiquantitative culture) were retrospectively reviewed. All liver transplant recipients received specific antibiotics according the susceptibility profiles of the PVB cultures, and all kidney transplant recipients received specific antibiotics according the susceptibility profiles of the PVB and urine cultures. Bacterial infection diseases transmission from donors of the liver and kidney transplant recipients were also retrospectively reviewed. RESULTS: The positive rates of the bacterial culture of the donor's bronchial aspiration, PVB, BCVC, TCVC, and urine were 46.4% (39/84), 20.2% (24/119), 15.8% (12/76), 11.1% (3/27), and 7.0% (8/115), respectively. Only 28.1% (9/32) of donors with positive cultures of PVB or urine received specific antimicrobial therapy before harvesting. Twenty-two livers and 46 kidneys from donors with systemic infection (positive PVB culture) were transplanted, and no case of bacterial infection diseases transmission occurred in the recipients. CONCLUSIONS: In the circumstance of donor systemic infection with positive bacterial culture of PVB, the liver and kidney can be transplanted safely with prophylactic antibiotics. Donors with systemic infection are not a contraindication for organ donation.

Lick of death: Capnocytophaga canimorsus is an important cause of sepsis in the elderly.

A 70-year-old Caucasian woman was treated for Capnocytophaga canimorsus septicaemia. The source of bacteraemia was very likely to be her household pet, an Italian greyhound. The patient presented with a presumed complex partial seizure but deteriorated rapidly with sepsis and multiorgan dysfunction. Neither scratch nor bite was established, although close petting including licks was reported. Blood cultures grew Gram-negative rods, identified by molecular techniques as C. canimorsus-a bacterium frequently isolated in the oral cavities of dogs and cats. A full recovery was made following 2 weeks of intensive care support and broad-spectrum antibiotics. No underlying immune dysfunction was found.

Prevention of sepsis prior to prostate biopsy.

PURPOSE: Urosepsis is the most feared complication of transrectal prostate biopsy. The incidence may be increasing from <1% to 2%-3% in contemporary series. Historically, fluoroquinolones have been effective antibiotic prophylaxis to prevent infective complications but antibiotic resistance is increasing. The increase in antibiotic resistance may contribute to reported increases in urosepsis and hospitalization after transrectal biopsy. This article will review other methods clinicians may employ to reduce the incidence of infective complications after prostate biopsy. MATERIALS AND METHODS: A systematic review of the literature was conducted using literature databases PubMed and Ovid MEDLINE in August 2015 in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) criteria. RESULTS: Effective strategies to reduce infective complications after transrectal prostate biopsy include augmented prophylaxis with other antibiotics, rectal swab culture directed antibiotic prophylaxis or a transperineal biopsy approach. Needle disinfection, minimizing the number of biopsy needles and rectal disinfectants may also be of use. These methods may be of particular utility in patients with risk factors for developing urosepsis such as recent antibiotic use and overseas travel. CONCLUSIONS: The scientific literature describes various techniques designed to reduce infective complications caused by prostate biopsy. Clinicians should consider incorporating these novel techniques into their contemporary practice.