High Risk For Invasive Infections Research Articles

Etiological characterization of invasive non-typhoid Salmonella strains in Guangdong Province from 2018 to 2022

Objective: To understand the serotype distribution, drug resistance and molecular characterization of invasive non-typhoid Salmonella (iNTS) in Guangdong Province from 2018 to 2022 and provide scientific evidence for the prevention and treatment of blood flow infection caused by Salmonella. Methods: Serological identification, antimicrobial susceptibility testing, multilocus sequence typing (MLST), and whole genome sequencing were performed on Salmonella isolated from blood and stool samples in Guangdong from 2018 to 2022. Simultaneously, annotated the sequencing results for drug resistance genes and virulence factors by a microbial gene annotation system. Results: The 136 iNTS strains were divided into 25 serotypes, and Salmonella enteritidis accounted for 38.24% (52/136). The OR of other iNTS serotypes were calculated with Salmonella typhimurium as the control. The OR values of Oreninburg, Rysson, and Pomona serotypes were the highest, which were 423.50, 352.92, and 211.75, respectively. The drug resistance rate of iNTS was 0.74%-66.91%, which was lower than that of non-iNTS (3.90%-77.21%). The main iNTS of drug resistance were ampicillin and tetracycline, with resistance rates of 66.91% (91/136) and 50.00% (68/136), respectively, while the resistance rates to ciprofloxacin (5.88%,8/136), ceftazidime (5.88%,8/136), gentamicin (5.13%,7/136) and cefoxitin (0.74%, 1/136) were relatively low. iNTS carried a variety of drug-resistance genes and virulence factors, but no standard virulence factor distribution has been found. MLST cluster analysis showed that iNTS was divided into 26 sequence types, and ST11 accounted for 38.24% (52/136). Conclusions: The iNTS strains in Guangdong were dominated by Salmonella enteritidis, of which three serotypes, Oreninburg, Rison, and Pomona, may be associated with a higher risk of invasive infection during 2018 to 2022. iNTS was sensitive to clinical first-line therapeutic drugs (cephalosporins and fluoroquinolones), with highly diverse sequences and clear phylogenetic branches. ST11 was the local dominant clone group.

Uptake of vaccination in older Indian patients with cancer: A cross-sectional observational study

ABSTRACT Export Background: Older patients with cancer are at a higher risk of invasive infections. Vaccination is an effective approach to decrease the mortality and morbidity associated with infections. Objectives: Our primary objective was to evaluate the proportion of older patients with cancer who had received routine vaccinations against pneumococcal, influenza, and coronavirus disease 2019 (COVID-19). Our secondary objective was to identify the factors associated with vaccine uptake such as age, sex, education, marital status, comorbidities, and place of residence. Materials and Methods: This cross-sectional observational study was conducted in the geriatric oncology outpatient clinic of the Department of Medical Oncology at the Tata Memorial Hospital, a tertiary care cancer hospital in Mumbai, India, from February 2020 to January 2023. We included all patients aged ≥60 years who were evaluated in the geriatric oncology clinic during the study period and for whom the immunization details were available. The uptake of COVID-19 vaccine was calculated from March 2021 onwards, which was when the COVID-19 vaccine became available to patients aged ≥60 years in India. Results: We enrolled 1762 patients; 1342 (76.2%) were male. The mean age was 68.4 (SD, 5.8) years; 795 (45%) patients were from the west zone of India. Only 12 (0.68%) patients had received the pneumococcal vaccine, and 13 (0.7%) had received the influenza vaccine. At least one dose of the COVID-19 vaccine had been taken by 1302 of 1562 patients (83.3%). On univariate logistic regression, education, marital status, geographic zone of residence, and primary tumor site were correlated with the uptake of COVID-19 vaccine. Factors associated with a greater COVID-19 vaccine uptake included education (up to Std 10 and higher vs. less than Std 10: Odds Ratio [OR], 1.46; 95% confidence interval [CI], 1.07-1.99; P = 0.018, and illiterate vs. less than Std 10: OR, 0.70; 95% CI, 0.50-0.99; P = 0.041), marital status (unmarried vs. married: OR, 0.27; 95% CI, 0.08-1.08; P = 0.046, and widow/widower vs. married: OR, 0.67; 95% CI, 0.48-0.94; P = 0.017), lung and gastrointestinal vs. head-and-neck primary tumors (lung cancer vs. head-and-neck cancer: OR, 1.60; 95% CI, 1.02–2.47; P = 0.038, and gastrointestinal vs .head-and-neck cancer: OR, 2.18; 95% CI, 1.37-3.42; P < 0.001), and place of residence (west zone vs. central India: OR, 0.34; 95% CI, 0.13-0.75; P = 0.015). Conclusion: Fewer than 1 in 100 older Indian patients with cancer receive routine immunization with influenza and pneumococcal vaccines. Hearteningly, the uptake of COVID-19 vaccination in older Indian patients with cancer is over 80%, possibly due to the global recognition of its importance during the pandemic. Similar measures as those used to increase the uptake of COVID-19 vaccines during the pandemic may be beneficial to increase the uptake of routine vaccinations (Clinical Trials Registry, India: CTRI/2020/04/024675).

Vaccination status in patients at risk for invasive disease with encapsulated bacteria at a children's hospital in the City of Buenos Aires.

Introduction. The Ministry of Health has established specific vaccines for people at high risk for invasive infections with encapsulated bacteria (EB). There is currently no information about compliance with the vaccination schedule. Our objective was to assess EB vaccination status in subjects ≤ 18 years with risk factors. Population and methods. Observational, analytical study with a survey to parents of subjects aged ≤ 18 years with HIV, asplenia and/or complement deficiency attending a vaccination center at a children's hospital between October 2020 and September 2021. Sociodemographic and clinical data were collected. Their vaccination status for the EB pneumococcus, meningococcus, and Haemophilus influenzae type b (Hib), their regular vaccination and flu vaccination schedules were assessed. The vaccine hesitancy scale (VHS) was administered: range 10-50. The association between the study variables and EB vaccination was analyzed using logistic regression (OR, 95% CI). The REDCap® database and the STATA ® v.14 software were used. Results. A total of 104 subjects participated; mean age: 9.9 years (SD: 4.4). Asplenia: 91.3%, HIV: 7.6%, and complement deficiency: 0.9%. Socioeconomic level: relative poverty: 38.4%, followed by middle class: 37.5%. Complete vaccination status: meningococcal vaccine 45%, pneumococcal vaccine: 42%, Hib: 97%. The regular vaccination and flu vaccination schedules were up-to-date in 77.9% and 61.5% of cases, respectively. Mean VHS score: 41.9 (SD: 3.2). No significant associations were observed between variables and EB vaccination status. Conclusions. A high percentage of subjects had not completed neither their EB vaccination nor their regular or their flu vaccination schedules. Caregivers' confidence in vaccines was high.

A wide clinical spectrum of pulmonary affection in subjects with community-acquired Klebsiella pneumoniae liver abscess (CA-KPLA)

BackgroundKlebsiella pneumoniae is a major pathogen of bacterial liver abscess in Asia. Particularly, patients with community-acquired Klebsiella pneumoniae liver abscess (CA-KPLA) tend to have a higher risk of invasive infection and pulmonary is a common invasive infectious site, making it a global clinical crisis. Therefore, considerable attention should be focused on the early prediction and active treatment strategies of such patients. MethodsThe clinical data of 127 CA-KPLA cases hospitalized from January 2017 to February 2022 were collected from a single center. Risk factors were analyzed by the use of univariable and multivariable analysis. Furthermore, independent risk factors of pulmonary affection were utilized to construct a predictive nomogram. ResultsThe incidence of pulmonary affection in KPLA patients was 57.5% (73/127) and the majority manifested as nodular lesions with cavities and pleural effusion in chest CT images. Based on the predictive nomogram, the SOFA score (>2) was defined as the most dominant independent risk factor for the occurrence of pulmonary affection, followed by the maximum diameter of liver abscess (>3 cm), multiple liver abscesses, bacteremia, and badly-controlled diabetes sequentially. The validation of this nomogram also demonstrated good discriminative ability and satisfactory consistency. Finally, early drainage of liver abscess, initial combinational antibiotics, and early Carbapenem-including antibiotic usage were established as favorable factors for therapy in pulmonary affected CA-KPLA patients. ConclusionThis study provided an effective model for the early prediction of pulmonary affection in patients with CA-KPLA and some rational strategies for their early therapeutic remission.

Targeted Staphylococcus aureus decolonization in acute inpatient and intensive care settings of an academic medical center

Background:Staphylococcus aureus is a common cause of healthcare associated infections and is associated with high mortality. S. aureus colonization of skin and mucosa contributes to its pathogenesis. Universal S. aureus decolonization reduces methicillin-resistant S. aureus (MRSA) and other bloodstream infections among ICU patients. However, universal decolonization in acute-care settings has not shown a similar benefit. We describe a targeted decolonization protocol implemented at a large academic hospital across acute-care and intensive care settings. We assessed the impact of decolonization on S. aureus–related infections. Methods: Adults admitted in 2018–2019 to the medicine, oncology, transplant, and ICU services were screened for S. aureus colonization using nasal swabs for MRSA/MSSA by culture. Those with S. aureus detected underwent decolonization with 5 days of chlorhexidine 2% baths and mupirocin intranasal ointment. Decolonization was considered complete if given for 5 days. The primary outcome was S. aureus invasive infection from hospital day 3 until discharge, defined by positive clinical cultures from sterile sites. Secondary outcomes included 30-day readmission and 30-day mortality. The control population was patients with negative MRSA/MSSA nasal screening in the same hospital units. Results: In total, 4,465 (23%) of 19,065 screening tests were positive for MSSA (75%) or MRSA (25%). The median age was 69 years (IQR, 56–80), and the median length of stay (LOS) was 6 days (IQR, 4–10). Among patients with LOS ≥3 days, 541 (16%) completed decolonization and 2,161 (64%) received no decolonization. The rate of complete decolonization increased to 35% among those with LOS ≥ 7 days. In total, 802 screened patients developed invasive S. aureus infections. Of 4,437 colonized patients, 536 (12%) had invasive infections, compared with 265 (2.1%) invasive infections in 12,917 noncolonized patients. Among patients with S. aureus colonization, 24% of decolonized patients developed invasive infection and 13% of patients who were not decolonized developed invasive infection. Rates of 30-day readmission and mortality were 28% and 10%, respectively, among fully decolonized patients, versus 20% and 6.6% among those receiving no decolonization. Conclusions: These data provide an assessment of the efficacy of a targeted screening and decolonization program. Although decolonization did not reduce rates of invasive infection or secondary outcomes, further analysis is needed. Patients with longer lengths of stay are more likely to receive full decolonization but are also at higher risk of invasive infection, which may contribute to our unexpected results.Funding: NoneDisclosures: None

LmTraceMap: A Listeria monocytogenes fast-tracing platform for global surveillance.

Listeria monocytogenes can cause listeriosis, and people with hypoimmunity such as pregnant women, infants and fetuses are at high risk of invasive infection. Although the incidence of listeriosis is low, the fatality rate is high. Therefore, continual surveillance and rapid epidemiological investigation are crucial for addressing L. monocytogenes. Because of the popularity of next-generation sequencing, obtaining the whole-genome sequence of a bacterium is easy. Several genome-based typing methods are available, and core-genome multilocus sequence typing (cgMLST) is the most recognized methods. Using cgMLST typing to compare L. monocytogenes whole-genome sequences (WGS) with those obtained across distinct regions is beneficial. However, the concern is how to incorporate the powerful cgMLST method into investigations, such as by using source tracing. Herein, we present an easy-to-use web service called–LmTraceMap (http://lmtracemap.cgu.edu.tw/hua_map/test/upload.php; http://120.126.17.192/hua_map/test/upload.php) that can help public-health professionals rapidly trace closely related isolates worldwide and visually inspect them in search results on a world map with labeled epidemiological data. We expect the proposed service to improve the convenience of public health investigations.

Complete genome and plasmid sequences of Staphylococcus aureus strain COL52-A5 isolated from a persistent nasal carrier

Persistent colonization with Staphylococcus aureus is associated with a higher risk of invasive infections. With increasing rates of colonization, especially with antibiotic-resistant strains, it may be useful to identify specific characteristics of colonization that confer a greater infection risk. Therefore, whole-genome sequencing (WGS) of an S. aureus strain isolated from a medical student identified as a persistent carrier in Cartagena, Colombia, was performed to better characterize the strain and to identify genetic components associated with virulence and antimicrobial resistance. Antimicrobial susceptibility testing was performed for several antibiotics. Total genomic DNA was extracted and WGS was performed on a PacBio RS II sequencing platform. Whole-genome assembly was generated using PacBio SMRT Analysis v.2.3.0 and HGAP v.1.2. In silico analysis of the chromosomal and plasmid components of this strain was performed using tools available online. Strain COL52-A5 was identified as a Panton-Valentine leukocidin (PVL)-positive methicillin-resistant S. aureus (MRSA) carrying staphylococcal cassette chromosome mec (SCCmec) type IVa and was resistant to cefoxitin, erythromycin, clindamycin and tetracycline. The completely closed genome of strain COL52-A5 was 2 820 086 bp with a GC content of 32.84% and it harboured one large plasmid, two active prophages, five antimicrobial resistance determinants and several virulence factors. The allelic profile was consistent with sequence type ST923 (CC8). Genome analysis of strain COL52-A5 found numerous virulence and resistance factors. Further comparison of genomic sequences from persistent and intermittent strains is required to gain insights into the genomic features that favour persistent carriage in healthy individuals.

The Importance of Environmental Screening in a Methicillin-Resistant Staphylococcus aureus (MRSA) Outbreak Investigation in a Transplant Unit

Background: Methicillin-resistant Staphylococcus aureus (MRSA) colonization conveys a higher risk of invasive infection. The transplant cohort is a group of immunocompromised patients who are at higher risk of infection. We conducted an outbreak investigation of hospital-acquired MRSA colonization within the transplant unit, which led to the discovery of positive isolates within our environment and to changes in our hospital disinfection policies. Methods: Our transplant unit consists of 8 single, positive-pressure rooms housed separately at the side of a larger ward. Staffing from this unit differs from the rest of the shared ward that houses up to 60 patients. As part of hospital screening, we found that a patient admitted for a stem-cell transplant had acquired nosocomial MRSA colonization. Given the unusual occurrence of such an event, a root-cause analysis was conducted. Results: A meeting was convened together with nursing, medical staff, and ancillary staff. Identified areas of potential transmission were deemed equipment, staff, and patients, and screening was performed. Shared equipment included the portable electrocardiogram (ECG) machines and portable x-ray machines and boards. In particular, ECG machines were shared with the adjoining nontransplant oncology ward. The usual practice was to clean the machine after use but not prior to the next use. This was deemed a possible exposure risk in view of a recent MRSA outbreak in a separate section of the ward. Positive isolates were found on both the x-ray and ECG machines. All healthcare workers were screened and were negative for MRSA. Furthermore, 7 patients admitted during the same time period were also screened for MRSA and were negative. Given the concurrent outbreak within the ward, pulsed-field gel electrophoresis was performed for all MRSA isolates obtained and the outbreak strain. These were found to be nonclonal (Table 1). Work processes for both the cleaning of ECG and x-ray machines were enhanced and modified. Hand hygiene measures to ward and radiology staff were reinforced. Thus far, no further cases have been detected. Conclusions: The environment is an important part of outbreak investigation. Shared equipment is often overlooked during day to day processes but should not be neglected. This can result in changes to hospital disinfection policy.Funding: NoneDisclosures: Indumathi Venkatachalam reports receiving honoraria for speaking engagements for bioMérieux and Pfizer and serving on an expert panel for MSD Pharma.

NONTYPEABLE HAEMOPHILUS INFLUENZAE VENTRICULITIS COMPLICATED BY HYDROCEPHALUS IN A PATIENT WITH SICKLE CELL DISEASE

SESSION TITLE: Fellows Critical Care Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: October 18-21, 2020 INTRODUCTION: Community-acquired purulent ventriculitis is very rare. We present a case of community-acquired purulent nontypeable Haemophilus influenzae meningitis with ventriculitis requiring cerebrospinal fluid diversion. CASE PRESENTATION: 46-year-old female with sickle cell disease presented in late fall with two days of headache, fever, and confusion. On arrival, she was febrile to 103F. On exam, she was agitated and unable to follow commands. Laboratory studies showed a white blood cell count of 23,000 (94% neutrophils), and procalcitonin 36 mg/dL. Blood and urine cultures were collected. The patient was given dexamethasone, vancomycin, meropenem (anaphylactic to penicillin), acyclovir, and doxycycline for community-acquired meningoencephalitis. CT Brain was consistent with cerebral edema. The patient required intubation for airway protection. Lumbar puncture showed purulent cerebrospinal fluid with opening pressure 21. CSF protein was 900, glucose 1, and 24,000 neutrophils. Gram stain showed numerous gram negative coccobacilli. MRI Brain showed layering debris within the ventricles and hydrocephalus. Due to intracranial hypertension, mannitol was given and an external ventricular drain placed. Blood and CSF cultures grew non-type B Haemophilus influenzae. The patient completed 14 days of ceftriaxone and was eventually extubated and ventriculostomy removed. DISCUSSION: Anatomical and functional asplenia poses high risk for invasive infections with encapsulated organisms such as S. pneumoniae, N. meningitidis, and H. influenzae. However, we present a case of community-acquired nontypeable H influenza meningitis with associated ventriculitis requiring CSF diversion. Nontypeable Haemophilus species lack a polysaccharide capsule for which splenic function provides less immunity. Serotype B was a common invasive pathogen prior to the institution of Hib vaccination in 1987. Nontypeable H influenzae is a common pathogen in otitis media in children and exacerbations of COPD in adults. Invasive diseases such as bacteremia and pneumonia are mostly seen at the extremes of age. Our patient is also unique in that she developed purulent ventriculitis complicated by hydrocephalus. Hydrocephalus complicates community-acquired bacterial meningitis in about 5% of cases and is associated with high mortality. H influenza ventriculitis is a rare condition and is mostly described in children and patient’s after neurosurgical CNS manipulation. CONCLUSIONS: We present a case of community-acquired nontypeable Haemophilus influenzae meningitis with ventriculitis. This case is unique in that the patient had purulent ventriculitis required CSF diversion. Community-acquired purulent ventriculitis is very rare without neurosurgical manipulation or indwelling CSF drainage catheters. Also, nontypeable H flu is an uncommon pathogen in the central nervous system and usually affects the respiratory tract. Reference #1: Eldere, J.V., Slack, M, Ladhani,Shamez, Cripps, A. Non-typeable Haemophilus infl uenzae, an under-recognised pathogen.Lancet Infect Dis 2014; 14: 1281–92. Reference #2: Bakaletz, L, Novotny, L. NontypeableHaemophilusinfluenzae(NTHi). Trends in Microbiology, August 2018,Vol. 26,No.8. Reference #3: Langereis, J, Jonge, M. Invasive Disease Caused by Nontypeable Haemophilus influenzae. Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 21, No. 10, October 2015. DISCLOSURES: No relevant relationships by Andrew Holt, source=Web Response No relevant relationships by Scott Sinclair, source=Web Response

555. The Burden of Invasive Staphylococcus Aureus Disease Among Native Americans on the Navajo Nation

BackgroundNative Americans in the southwestern United States (US) may be at higher risk for invasive infections due to Staphylococcus aureus. The objective of this study was to determine the burden of invasive S. aureus among Native Americans on the Navajo Nation.MethodsProspective population and laboratory-based surveillance for invasive S. aureus infections was conducted from May 2016 through April 2018. A case was defined as a Native American individual living on or around the Navajo Nation with S. aureus isolated from a normally sterile body site. Incidence rates were calculated using the Indian Health Service User Population from 2016 and 2017 as the denominators for Years 1 and 2, respectively. Age-standardized incidence rates were calculated using US Census data from 2015 as the reference group.Results363 cases were identified (Year 1: 159; Year 2: 204). Most cases were adults (96.9%; median age: 56.0 years) and had ≥1 underlying medical condition (94.5%), of which the most common were diabetes (63.2%), hypertension (39.1%), and obesity (37.2%). 38.0% of cases were categorized as community acquired and 28.7% of infections were methicillin-resistant (MRSA). 83.2% of cases were hospitalized, 10.7% required amputation, and 6.5% died within 30 days of the initial culture. The overall incidence of invasive S. aureus was 74.4 per 100,000 persons (95% confidence interval [CI]: 67.1, 82.4) with a significantly higher incidence in the second year (Year 1: 64.9; Year 2: 84.0; incidence rate ratio: 1.29; 95% CI: 1.05, 1.59). The overall incidence of invasive MRSA was 21.3 per 100,000 persons (95% CI: 17.6, 25.8) with no significant difference by year (Year 1: 21.2; Year 2: 21.4; incidence rate ratio: 1.01; 95% CI: 0.69, 1.48). The incidence of invasive S. aureus and MRSA increased with age and was highest among individuals ≥65 years of age. The overall age-standardized incidence of invasive MRSA was 25.9 per 100,000 persons (Year 1: 26.0; Year 2: 25.7; for comparison US 2015 general population: 18.8 per 100,000 persons).ConclusionThe Navajo Nation has a higher burden of invasive MRSA than the general US population. Further research is needed to evaluate trends over time and identify prevention strategies and opportunities for intervention.Disclosures All authors: No reported disclosures.

Safety and immunogenicity of pneumococcal conjugate vaccines in preterm infants

ABSTRACTIntroduction: The introduction of pneumococcal conjugate vaccines (PCVs) in the routine immunization program has resulted in a significant decline in invasive pneumococcal diseases (IPD) around the world. Preterm infants are a special group at a high risk of invasive infection by encapsulated bacteria. However, their slow growth accrual and prolonged hospital stay frequently lead to delays in immunization, which contributes to their risk for severe infections.Areas covered: Authors reviewed the published immunogenicity and safety of the use of PCVs in preterm infants.Expert opinion: PCVs are safe and effective for use in low birth weight and in-hospital preterm infants. Local and systemic reactions are similar for both term and preterm populations. Reports were inconsistent on the risk of apnea, therefore hospitalized extremely premature infants should be kept under observation for at least 48 h after immunization.

The diabetic foot: Pathophysiology, evaluation, and treatment

The pathophysiology of the diabetic foot ulcer and soft-tissue infection is due to neuropathy, trauma, and, in many patients, concomitant peripheral artery occlusive disease. Diabetic neuropathy results in foot deformity, leading to increased skin pressure with walking. Once a foot ulcer develops, the limb is at high risk for invasive infection and, when combined with peripheral artery occlusive disease, the patient should be considered to have critical limb ischemia. A multidisciplinary approach to care for the diabetic foot is recommended, which includes annual (3-month intervals in high-risk patients) assessments by a primary care physician and referral to a podiatrist and vascular surgeon for diabetics with a foot ulcer for evaluation of foot arterial perfusion and off-loading therapy to reduce plantar skin pressure with walking. When invasive foot infection develops and tissue beneath the fascia is involved, inpatient care is recommended for systemic antibiotic therapy, vascular laboratory testing of artery limb perfusion, and surgical debridement of infected tissue. The goals of treatment are to achieve a healed foot and keep the patient ambulatory.

Intestinal Adenovirus Shedding Before Allogeneic Stem Cell Transplantation Is a Risk Factor for Invasive Infection Post-transplant

Human adenoviruses (HAdV) are a major cause of morbidity and mortality in pediatric human stem cell transplant (HSCT) recipients. Our previous studies identified the gastrointestinal tract as a site of HAdV persistence, but the role of intestinal virus shedding pre-transplant for the risk of ensuing invasive infection has not been entirely elucidated. Molecular HAdV monitoring of serial stool samples using RQ-PCR was performed in 304 children undergoing allogeneic HSCT. Analysis of stool and peripheral blood specimens was performed pre-transplant and at short intervals until day 100 post-HSCT. The virus was detected in the stool of 129 patients (42%), and 42 tested positive already before HSCT. The patients displaying HAdV shedding pre-transplant showed a significantly earlier increase of intestinal HAdV levels above the critical threshold associated with high risk of invasive infection (p<0.01). In this subset of patients, the occurrence of invasive infection characterized by viremia was significantly higher than in patients without HAdV shedding before HSCT (33% vs 7%; p<0.0001). The data demonstrate that intestinal HAdV shedding before HSCT confers a greatly increased risk for invasive infection and disseminated disease post-transplant, and highlights the need for timely HAdV monitoring and pre-emptive therapeutic considerations in HSCT recipients.

High Oral Carriage of Non-albicans Candida spp. among HIV-infected individuals.

Non-albicans Candida (NAC) spp. in immunocompromised patients are linked to invasive infections with narrow treatment choice. This study aimed at comparing the oral colonization of NAC spp. between HIV and non-HIV infected individuals in Mwanza, Tanzania. Oral rinse of 351 HIV-infected and 639 non-HIV infected individuals were collected between March and July 2015. Phenotypic identifications of Candida spp. was done using Candida Chromogenic agar and confirmed by MALDI-TOF MS. NAC spp. were detected in 36/351 (10.3%) HIV-infected individuals compared to 28/639 (4.4%) of non-HIV infected individuals; P=0.0003. In HIV infected individuals, commonly isolated NAC spp. were Candida tropicalis, 10(2.8%), C. krusei (Issatschenki orientalis) 9(2.6%) and C. glabrata 8(2.3%). While for non-HIV infected individuals C. dubliniensis 8(1.3%) and C. tropicalis 5(0.9%) were commonly detected. As CD4 count/μl decreases by one unit the risk of being colonized by NAC spp. among HIV infected individuals increases by 1% (OR 1.01, 95% CI; 1.001-1.004, P=0.001). The prevalence of NAC spp. is high among HIV-infected individuals with low CD4 count placing them at higher risk of invasive infections. Further studies to investigate the role of NAC spp. in causing invasive infections among immunocompromised patients are recommended.

Evaluation of Panfungal Marker (1,3)-⃞-D-Glucanin Diagnosis of Invasive Infections with Candida Species

Abstract Introduction. Although blood culture is considered a gold standard in diagnosis of invasive infections, it is still not reliable and fast enough for diagnosis of candidemia. Determination of serum (1,3)-⃞-D-glucan is a highly sensitive and specific test for invasive mycosis, and could probably be of benefit to patients with high risk for invasive infections with Candida species. Aim. The aim of this study was to prospectively evaluate the diagnostic performance of serum (1.3)-⃞-Dglucan BDG (Fungitell) assay, in comparison with blood culture, for diagnosis of invasive infections with Candida species. Methods. Blood and sera from 120 patients divided in 4 groups, hospitalized at the University clinics in Skopje, during a 2-year period, were investigated for invasive Candida infections. Blood was examined with conventional methods (automated BacT/Alert system, Gram stain and culture on fungal media). Identification of Candida species was performed with VITEK-2 system. Serum (1,3)-⃞-D-glucan was determined by means of Fungitell assay. Results. Positive blood culture was registered in 23.33%, 43.33%, 23.8% and in 3.33% of samples only in groups I, II, III and IV, respectively. Positive findings with (1,3)-⃞-D-glucan Fungitell assay at the same time with blood culture were detected in 83.33%, 76.67%, 30% and 26.67% in groups I, II, III and IV, respectively. The average concentration of BDG was highest in group I, followed by group II, group IV and group III. Conclusion. Our results suggest that a positive (1,3)-⃞-D-glucan assay could be a superior test in addition to the blood culture for diagnosis of candidemia and highlights the value of this test as a diagnostic adjunct in the serodiagnosis of an invasive candidiasis.

Persistence and reactivation of human adenoviruses in the gastrointestinal tract

Reactivation of persistent human adenoviruses (HAdVs) is associated with high morbidity and mortality in paediatric haematopoietic stem cell transplant (HSCT) recipients. Although invasive HAdV infections mainly arise from the gastrointestinal (GI) tract, the specific sites of HAdV persistence are not well characterised. We prospectively screened biopsies from 143 non-HSCT paediatric patients undergoing GI endoscopy and monitored serial stool specimens from 148 paediatric HSCT recipients for the presence of HAdV by real-time PCR. Persistence of HAdV in the GI tract was identified in 31% of children, with the highest prevalence in the terminal ileum. In situ hybridisation and immunohistochemistry identified HAdV persistence in lymphoid cells of the lamina propria, whereas biopsies from five transplant recipients revealed high numbers of replicating HAdV in intestinal epithelial cells. The prevalence of HAdV species, the frequencies of persistence in the GI tract and reactivations post transplant indicated a correlation of intestinal HAdV shedding pre-transplant with high risk of invasive infection. HAdV persistence in the GI tract is a likely origin of infectious complications in immunocompromised children. Intestinal lymphocytes represent a reservoir for HAdV persistence and reactivation, whereas the intestinal epithelium is the main site of viral proliferation preceding dissemination. The findings have important implications for assessing the risk of life-threatening invasive HAdV infections.

Risk of MRSA Infection in Patients with Intermittent versus Persistent MRSA Nares Colonization.

To determine the relative risk of invasive methicillin-resistant Staphylococcus aureus (MRSA) infection among non-colonized (NC) patients, intermittently colonized (IC) patients, and persistently colonized (PC) patients. Observational cohort study of patient data collected longitudinally over a 41-month period. Department of Veterans Affairs Eastern Colorado Healthcare System, a tertiary care medical center. Any patient who received ≥5 MRSA nasal swab tests between February 20, 2010, and July 26, 2013. In total, 3,872 patients met these criteria, 0 were excluded, 95% were male, 71% were white, and the mean age was 62.9 years on the date of study entry. Patients were divided into cohorts based on MRSA colonization status. Physicians reviewed medical records to identify invasive infection and were blinded to colonization status. Cox and Kaplan-Meier analyses were used to assess the relationship between colonization status and invasive infection. In total, 102 patients developed invasive MRSA infections, 16.3% of these were PC patients, 11.2% of these were IC patients, and 0.5% of these were NC patients. PC patients were at higher risk of invasive infection than NC patients (hazard ratio [HR] 36.8; 95% CI, 18.4-73.6; P<.001). IC patients were also at higher risk than NC patients (HR, 22.8; 95% CI, 13.3-39.3; P<.001). The difference in risk between PC and IC patients was not statistically significant (HR, 1.61; 95% CI, 0.94-2.78, P=.084). Alternate analysis methods confirmed these results. The risk of invasive MRSA infection is much higher among PC and IC patients, supporting routine clinical testing for colonization. However, this risk is similar among PC and IC patients, suggesting that distinguishing between the 2 colonization states may not be clinically important.

Short-Term In-Vitro Expansion Improves Monitoring and Allows Affordable Generation of Virus-Specific T-Cells against Several Viruses for a Broad Clinical Application

Adenoviral infections are a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT) in pediatric patients. Adoptive transfer of donor-derived human adenovirus (HAdV)-specific T-cells represents a promising treatment option. However, the difficulty in identifying and selecting rare HAdV-specific T-cells, and the short time span between patients at high risk for invasive infection and viremia are major limitations. We therefore developed an IL-15-driven 6 to 12 day short-term protocol for in vitro detection of HAdV-specific T cells, as revealed by known MHC class I multimers and a newly identified adenoviral CD8 T-cell epitope derived from the E1A protein for the frequent HLA-type A*02∶01 and IFN-γ. Using this novel and improved diagnostic approach we observed a correlation between adenoviral load and reconstitution of CD8+ and CD4+ HAdV-specific T-cells including central memory cells in HSCT-patients. Adaption of the 12-day protocol to good manufacturing practice conditions resulted in a 2.6-log (mean) expansion of HAdV-specific T-cells displaying high cytolytic activity (4-fold) compared to controls and low or absent alloreactivity. Similar protocols successfully identified and rapidly expanded CMV-, EBV-, and BKV-specific T-cells. Our approach provides a powerful clinical-grade convertible tool for rapid and cost-effective detection and enrichment of multiple virus-specific T-cells that may facilitate broad clinical application.

First outbreak of VIM-2 metallo-β-lactamase-producing Pseudomonas aeruginosa in The Netherlands: microbiology, epidemiology and clinical outcomes

This study was designed to investigate the prevalence and characteristics of metallo-β-lactamase (MBL)-producing Pseudomonas aeruginosa in a tertiary care centre in The Netherlands, a country that is considered to have a low prevalence of antibiotic-resistant bacteria. Imipenem-resistant P. aeruginosa isolates cultured from clinical specimens during 2008–2009 were analysed phenotypically and molecularly by polymerase chain reaction (PCR) with sequencing. Genotyping was performed by multiple-locus variable-number tandem repeat (VNTR) analysis (MLVA). Clinical information was obtained by electronic chart review for all patients infected or colonised with an imipenem-resistant P. aeruginosa isolate that was included in the study. In total, 106 imipenem-resistant P. aeruginosa isolates were included. The bla VIM-2 gene was detected in 35/106 isolates (33%) and was associated with integrons. Compared with non-MBL-producing imipenem-resistant P. aeruginosa, VIM-2 MBL-producing isolates showed higher rates of multidrug resistance. Patients with VIM-2 MBL-producing isolates were more likely to be admitted to the Intensive Care Unit (ICU) and had a higher risk of invasive infection, including development of bacteraemia. MLVA identified two separate VIM-2 MBL-producing clones, responsible for outbreaks in the ICU but also affecting 10 other departments. This is the first reported outbreak of VIM-2 MBL-producing P. aeruginosa in The Netherlands. Once introduced, VIM-2 MBL-producing P. aeruginosa cause significant infections and are easily spread within the hospital setting.

Implementation of Goal-Directed Therapy for Children With Suspected Sepsis in the Emergency Department

Suboptimal care for children with septic shock includes delayed recognition and inadequate fluid resuscitation. To describe the implementation of an emergency department (ED) protocol for the recognition of septic shock and facilitate adherence to national treatment guidelines. Root-cause analyses and morbidity and mortality conferences identified system problems with sepsis recognition and management. A group of ED and critical care physicians met to identify barriers and create solutions. To facilitate sepsis recognition, a computerized triage system alarmed on abnormal vital signs, and then toxic-appearing children or children at high risk for invasive infection were placed in a resuscitation room. To facilitate timely delivery of interventions, additional nursing, respiratory therapy, and pharmacy personnel were recruited. Fluids were administered via syringe delivery; standardized laboratory studies and antibiotics were ordered and prioritized. Frequent vital-sign measurements and interventions were documented on a graphical flow sheet to facilitate interpretation of physiologic response to therapy. After protocol initiation, there were 191 encounters in 167 patients with suspected sepsis. When compared with children seen before the protocol, time from triage to first bolus decreased from a median of 56 to 22 minutes (P < .001) and triage to first antibiotics decreased from a median of 130 to 38 minutes (P < .001). The protocol resulted in earlier recognition of suspected sepsis and substantial reductions in both time to receipt of time-sensitive interventions and a decrement in treatment variation.