Risk Of Infection Research Articles

In vitro mimicry of in vivo KPC mutations by ceftazidime-avibactam: phenotypes, mechanisms, genetic structure and kinetics of enzymatic hydrolysis

Ceftazidime-avibactam (CZA) is employed for the treatment of infections caused by Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-KP). Resistance to CZA is frequently linked to point mutations in the bla KPC. We conducted in vitro simulations of in vivo bla KPC mutations using CZA. Four pre-therapy KPC-KP isolates (K1, K2, K3, and K4) were evaluated, all initially exhibited susceptibility to CZA and produced KPC-2. The crucial distinction was that following CZA treatment, the bla KPC-2 mutated in K1, K2, and K3, rendering them resistant to CZA, while K4 achieved microbiological clearance, and bla KPC-2 remained unaltered. The induction assay identified various bla KPC-2 variants, including bla KPC-25, bla KPC-127, bla KPC-100, bla KPC-128, bla KPC-137, bla KPC-138, bla KPC-144 and bla KPC-180. Our findings suggest that the resistance of KPC-KP to CZA primarily results from the emergence of KPC variants, complemented by increased bla KPC expression. A close correlation exists between avibactam concentration and the rate of increased CZA minimum Inhibitory concentration, as well as bla KPC mutation. Inadequate avibactam concentration is more likely to induce resistance in strains against CZA, there is also a higher likelihood of mutation in the bla KPC-2 and the optimal avibactam ratio remains to be determined. Simultaneously, we selected a bla KPC-33-producing K. pneumoniae strain (mutated from bla KPC-2) and induced it with imipenem and meropenem, respectively. The bla KPC-2 was detected during the process, indicating that the mutation is reversible. Clinical use of carbapenems to treat KPC variant strains increases the risk of infection, as the gene can mutate back to bla KPC-2, rendering the strain even more cross-resistant to carbapenems and CZA.

Dipeptidyl peptidase-4 inhibitors and the risk of infection: A systematic review and meta-analysis of cardiovascular outcome trials

BACKGROUND Since adverse events during treatment affect adherence and subsequent glycemic control, understanding the safety profile of oral anti-diabetic drugs is imperative for type 2 diabetes mellitus (T2DM) therapy. AIM To evaluate the risk of infection in patients with T2DM treated with dipeptidyl-peptidase 4 (DPP-4) inhibitors. METHODS Electronic databases were searched. The selection criteria included randomized controlled trials focused on cardiovascular outcomes. In these studies, the effects of DPP-4 inhibitors were directly compared to those of either other active anti-diabetic treatments or placebo. Six trials involving 53616 patients were deemed eligible. We calculated aggregate relative risks employing both random-effects and fixed-effects approaches, contingent upon the context. RESULTS The application of DPP-4 inhibitors showed no significant link to the overall infection risk [0.98 (0.95, 1.02)] or the risk of serious infections [0.96 (0.85, 1.08)], additionally, no significant associations were found with opportunistic infections [0.69 (0.46, 1.04)], site-specific infections [respiratory infection 0.99 (0.96, 1.03), urinary tract infections 1.02 (0.95, 1.10), abdominal and gastrointestinal infections 1.02 (0.83, 1.25), skin structure and soft tissue infections 0.81 (0.60, 1.09), bone infections 0.96 (0.68, 1.36), and bloodstream infections 0.97 (0.80, 1.18)]. CONCLUSION This meta-analysis of data from cardiovascular outcome trials revealed no heightened infection risk in patients undergoing DPP-4 inhibitor therapy compared to control cohorts.

Viral infections and inborn errors of immunity.

The purpose of this focused review is to discuss unusual presentations of viral infections in the context of specific inborn errors of immunity. We will discuss hyper immunoglobulin E (IgE) syndromes, epidermodysplasia verruciformis, and X-linked agammaglobulinemia as examples of inborn errors of immunity associated with specific presentations of viral infection and disease. Advances in both genetic and viral diagnostics have broadened our understanding of viral pathogenesis in the setting of immune dysfunction and the variable phenotype of inborn errors of immunity. Dedicator of cytokinesis 8 (DOCK8) deficiency is now recognized as an inborn error of immunity within the hyper IgE syndrome phenotype and is associated with unusually aggressive cutaneous disease caused by herpes simplex and other viruses. Studies of patients with epidermodysplasia verruciformis have proven that rarely detected human papillomavirus subtypes may cause malignancy in the absence of adequate host defenses. Finally, patients with X-linked agammaglobulinemia may remain at risk for severe and chronic viral infections, even as immune globulin supplementation reduces the risk of bacterial infection. Susceptibility to viral infections in patients with inborn errors of immunity is conferred by specific, molecular defects. Recurrent, severe, or otherwise unusual presentations of viral disease should prompt investigation for an underlying genetic defect.

Mpox in people with HIV: A narrative review.

The 2022 global mpox outbreak disproportionately impacted people living with HIV. This review explores recent evidence on mpox in this group, focusing on clinical presentation, complications, treatment modalities and vaccine strategies. Recent studies have suggested that people with HIV diagnosed with mpox have a greater risk of proctitis and hospitalization compared with people without HIV. In addition, those with advanced immunosuppression face an elevated risk of severe mpox infection, which can lead to mortality. Comprehensive and prompt supportive care using antiretrovirals and mpox antivirals is crucial in this group. Although results from randomized clinical trials are still forthcoming, recent studies suggest that early initiation of tecovirimat can prevent disease progression in people with HIV. The non-replicative attenuated smallpox vaccine is well tolerated and effective in preventing monkeypox virus infections in people with HIV. Further studies are needed regarding long-term vaccine effectiveness for this population. Evaluating the risk of severe mpox in people living with HIV requires assessing the level of immune suppression and viral control. Universal access to vaccination is imperative to prevent the resurgence of future outbreaks.

A bi-functional nanofibrous composite membrane for wound healing applications.

Various wound dressings have been developed so far for wound healing, but most of them are ineffective in properly reestablishing the skin's structure, which increases infection risks and dehydration. Electrospun membranes are particularly interesting for wound dressing applications because they mimic the extracellular matrix of healthy skin. In this study, a potential wound healing platform capable of inducing synergistic antibacterial and antioxidation activities was developed by incorporating bio-active rosmarinic acid-hydroxyapatite hybrid (HAP-RA) with different contents (0.5, 1, and 1.5 wt.%) into the electrospun polyamide 6 (PA6) nanofibers. Then, polyethylene glycol (PEG) was introduced to the nanofibrous composite to improve the biocompatibility and biodegradability of the dressing. The results indicated that the hydrophilicity, water uptake, biodegradability, and mechanical properties of the obtained PA6/PEG/HAP-RA nanofibrous composite enhanced at 1 wt.% of HAP-RA. The nanofibrous composite had excellent antibacterial activity. The antioxidation potential of the samples was assessed in vitro. The MTT assay performed on the L929 cell line confirmed the positive effects of the nanofibrous scaffold on cell viability and proliferation. According to the results, the PA6/PEG/HAP-RA nanofibrous composite showed the desirable physiochemical and biological properties besides antibacterial and antioxidative capabilities, making it a promising candidate for further studies in wound healing applications.

Impact of previous treatment history and B-cell depletion treatment duration on infection risk in relapsing-remitting multiple sclerosis: a nationwide cohort study

BackgroundB-cell depletion displays striking effectiveness in relapsing-remitting multiple sclerosis (RRMS), but is also associated with increased infection risk. To what degree previous treatment history, disease-modifying therapy (DMT) switching pattern and...

The intake of solid fat and cheese may be associated with a reduced risk of Helicobacter pylori infection status: a cross-sectional study based on NHANES 1999–2000

BackgroundDiet plays an important role in Helicobacter pylori (HP) infection, and our objective was to investigate potential connections between dietary patterns, specific food groups, and HP infection status in U.S. adults.MethodsThe data for this study was obtained from the NHANES (National Health and Nutrition Survey) database for the year 1999–2000. This cross-sectional study involved the selection of adults aged 20 years and older who had undergone dietary surveys and HP testing. Factor analysis was employed to identify dietary patterns, and logistic regression models were utilized to assess the association between these dietary patterns and specific food groups with HP infection status.ResultBased on the inclusion and exclusion criteria, our final analysis included 2,952 individuals. The median age of participants was 51.0 years, and 48.7% were male. In the study population, the overall prevalence of HP infection was 44.9%. Factor analysis revealed three distinct dietary patterns: High-fat and high-sugar pattern (including solid fats, refined grains, cheese, and added sugars); Vegetarian pattern (comprising fruits, juices, and whole grains); Healthy pattern (encompassing vegetables, nuts and seeds, and oils). Adjusted results showed that the high-fat and high-sugar pattern (OR = 0.689, 95% CI: 0.688–0.690), vegetarian pattern (OR = 0.802, 95% CI: 0.801–0.803), and healthy pattern (OR = 0.717, 95% CI: 0.716–0.718) were all linked to a lower likelihood of HP infection. Further analysis of the high-fat and high-sugar pattern revealed that solid fats (OR = 0.717, 95% CI: 0.716–0.718) and cheese (OR = 0.863, 95% CI: 0.862–0.864) were protective factors against HP infection, while refined grains (OR = 1.045, 95% CI: 1.044–1.046) and added sugars (OR = 1.014, 95% CI: 1.013–1.015) were identified as risk factors for HP infection.ConclusionBoth the Vegetarian pattern and the Healthy pattern are associated with a reduced risk of HP infection. Interestingly, the High-fat and High-sugar pattern, which is initially considered a risk factor for HP infection when the score is low, becomes a protective factor as the intake increases. Within this pattern, animal foods like solid fats and cheese play a protective role, while the consumption of refined grains and added sugars increases the likelihood of HP infection.

Comparative retrospective assessment of the effectiveness and risk factors of fluoroquinolones, cephalosporines and selective antibiotic prophylaxis for transrectal prostate biopsy.

Despite increasing resistance of enterobacteria against fluoroquinolones (FLU), they are still widely used during transrectal prostate biopsy (TRPB). This study was designed to analyse infectious complications and risk factors between FLU, cephalosporines (CEPH) and selective other antibiotics (O-AB) used during TRPB. 664 patients were included retrospectively (152 FLU, 452 CEPH and 60 O-AB). Infectious complications were defined as: fever >38.0°C, in-house definition of complicated urinary tract infection (cUTI) (if all applied: fever >38.0°C, leucocytosis >11.000/µl and positive urine dipstick) or postinterventional bacteriuria. Hospitalisation rate, -duration and comorbidities were also assessed. Chi-Square and Fishers exact test were used for group comparison. Multivariate regression analysis assessed the association of comorbidities with infectious complications. FLU and CEPH were indifferent regarding infectious complications, however in the O-AB group significantly more common compared to FLU and CEPH (11.6%, 13.3%, 25%, p<0.05). Duration of hospital stay in CEPH was significantly shorter compared to FLU and O-AB (4.1 vs. 6.3 vs. 8.2 days, p<0.05). Arterial hypertension showed increased association with fever (OR 6.002 [1.178;30.597] p=0.031) and cUTI (OR 6.006 [1.207;29.891] p=0.029). Infectious complications were low and indifferent between FLU and CEPH but significantly more frequent in O-AB. Arterial hypertension was significantly associated with postinterventional fever and cUTI.

Analysis of somatic mutations in whole blood from 200,618 individuals identifies pervasive positive selection and novel drivers of clonal hematopoiesis.

Human aging is marked by the emergence of a tapestry of clonal expansions in dividing tissues, particularly evident in blood as clonal hematopoiesis (CH). CH, linked to cancer risk and aging-related phenotypes, often stems from somatic mutations in a set of established genes. However, the majority of clones lack known drivers. Here we infer gene-level positive selection in whole blood exomes from 200,618 individuals in UK Biobank. We identify 17 additional genes, ZBTB33, ZNF318, ZNF234, SPRED2, SH2B3, SRCAP, SIK3, SRSF1, CHEK2, CCDC115, CCL22, BAX, YLPM1, MYD88, MTA2, MAGEC3 and IGLL5, under positive selection at a population level, and validate this selection pattern in 10,837 whole genomes from single-cell-derived hematopoietic colonies. Clones with mutations in these genes grow in frequency and size with age, comparable to classical CH drivers. They correlate with heightened risk of infection, death and hematological malignancy, highlighting the significance of these additional genes in the aging process.

The role of glomerular filtration rate in AVF success: Should we intervene earlier?

End-stage kidney disease (ESKD) patients require life-sustaining kidney replacement therapies, with the natural arteriovenous fistula (AVF) being the preferred vascular access due to its low infection risk, high patency, and fewer complications. Factors like vessel diameter, gender, diabetes, age, and surgical technique influence AVF maturation. Our study focused on short-term AVF creation success, specifically examining estimated glomerular filtration rate (eGFR) levels using the CKD-EPI formula. Patients were categorized according to their eGFR levels to observe the effects of fistula timing and the severity of kidney disease. No significant demographic or outcome differences between eGFR groups have been observed except for gender. AVF maturation was notably associated with distal vein diameter (>2mm), while other factors did not significantly impact maturation rates. As a secondary outcome, it was concluded that the recording of patients' blood pressure values at preoperative and perioperative levels led to the conclusion that blood pressure levels may have an impact on fistula maturation. To ensure vascular access effectiveness, optimizing blood pressure, determining vein diameter, strategic AVF timing, and reducing catheter usage are crucial. Our study aimed to identify eGFR levels conducive to optimal AVF outcomes. Although significant results could not be obtained in this regard, it is considered worthwhile to re-examine the effect of blood pressure in secondary outcomes. Additionally, prospective studies may be appropriate for reevaluating the effect of GFR.

Prevalence of Intestinal Parasites among Diabetes Mellitus Patients in Tertiary Care Hospital

Intestinal parasitosis constitutes a serious problem of public health, especially in developing countries. Even though the population of immunocompromised individuals is growing, this is a primary cause of illness and mortality. Numerous studies have demonstrated that immunosuppressive medications, such as those used after transplantation, as well as immune suppression as a primary immunodeficiency in HIV infection, increase the possibility of infection and persistent states of carriage. People whose immune systems were weakened, like in the case of chronic internal disorders or abnormal metabolism, were thought to be more susceptible to infection. A group of metabolic non-communicable diseases known as diabetes mellitus (DM) are characterized by hyperglycemia or elevated blood sugar, which can be brought on by either inadequate secretion of insulin, insulin-resistant cells, or both. Parasitic infections in immunocompromised people are becoming more well-known as major opportunistic microorganisms that cause clinical illnesses. The goal of this research is to see how common intestinal parasite infections are in people with diabetes. The research was carried out at the Chandulal Chandrakar Memorial Medical College, Bhilai, Durg district of Chhattisgarh, India. From March to August 2020, diabetic patients who visited hospitals were studied in this cross-sectional study. This study comprised 188 diabetic individuals with type I or type II diabetes who were taking anti-diabetic medication. With a little spoon and a sterile, dry, leak-proof plastic container with a tight-fitting cover that had the patient’s name and identification number on it, the feces samples were taken. The container was then quickly sent to the parasitology lab of the microbiology department for processing. Stool samples were examined under three headings: macroscopic examination, microscopic examination, and formal ether concentration procedure. A total of 188 DM patients was included with data on socio-demographic characteristics, and from each patient stool sample were collected and processed. Out of which, 27 stool samples were positive for intestinal parasites; showed a prevalence of 14.36%. Female 16 (16.49%) revealed a greater frequency than that of men 11 (12.09%). The age range of 51 to 60 years old exhibited the highest incidence 8 (29.63 %). Stool samples were positive for intestinal parasites with one suffering from a dual infection. Various parasites were detected in which Entamoeba histolytica 10 (5.32%) was most common parasite to isolate followed by Ascaris lumbricoides 9 (4.79%) and Giardia lamblia 6 (3.19%) was least isolated parasite. The most prevalent isolated parasite was Entamoeba histolytica, which was followed by Cryptosporidium parvum. Diabetic patients have an increased risk of parasitic infections, particularly when they have the opportunistic infection Entamoeba histolytica. Patients with diabetes who have been diagnosed with Cryptosporidium parvum have a weaker immune system. Therefore, for the sake of societal welfare, people with diabetes mellitus should have routine stool examination screening for parasite infection.

Semiquantitative Risk Evaluation Reveals Drivers of African Swine Fever Virus Transmission in Smallholder Pig Farms and Gaps in Biosecurity, Tanzania

African swine fever (ASF) has remained persistent in Tanzania since the early 2000s. Between 2020 and 2021, pig farms in twelve districts in Tanzania were infected with ASF, and ≥4,804 pigs reportedly died directly due to the disease with disruption to livelihoods. We conducted semiquantitative field investigations and rapid risk assessment (RRA) to understand the risk factors and drivers of ASF virus (ASFV) amplification and transmission in smallholder pig farms, and determine the gaps in biosecurity through hazard profiling, focus group discussions and expert opinion. Outbreaks were connected by road and aligned along the pig product value chain and reported in the northern, central, and southern parts of Tanzania. The patterns of outbreaks and impacts differed among districts, but cases of ASF appeared to be self-limiting following significant mortality of pigs in farms. Movement of infected pigs, movement of contaminated pig products, and fomites associated with service providers, vehicles, and equipment, as well as the inadvertent risks associated with movements of animal health practitioners, visitors, and scavengers were the riskiest pathways to introduce ASFV into smallholder pig farms. Identified drivers and facilitators of risk of ASFV infection in smallholder pig farms were traders in whole pigs, middlemen, pig farmers, transporters, unauthorized animal health service providers, and traders in pork. All identified pig groups were susceptible to ASFV, particularly shared adult boars, pregnant and lactating sows, and other adult females. The risk of ASF for smallholder pig farms in Tanzania remains very high based on a systematic risk classification. The majority of the farms had poor biosecurity and no single farm implemented all identified biosecurity measures. Risky practices and breaches of biosecurity in the pig value chain in Tanzania are profit driven and are extremely difficult to change. Behavioural change communication must target identified drivers of infections, attitudes, and practices.

Effectiveness of cocoon strategy vaccination on prevention of influenza-like illness in young infants

ABSTRACT During the initial half-year of their existence, infants cannot receive the influenza vaccine, yet they face the greatest susceptibility to severe influenza complications. In this study, we seek to determine whether influenza vaccination of maternal and household contacts is associated with a reduced risk of influenza-like illness (ILI) and severe acute respiratory infection (SARI) in infants. This work was prospectively conducted during the influenza season. A total of 206 infants were included in this study. The percentage of infants with only the mother vaccinated is 12.6% (n:26), and the percent of infants with all household contacts vaccinated is 16% (n:33). Among the infants with only the mother vaccinated, the effectiveness of influenza vaccine is estimated as 35.3% for ILI and 41.3% for SARI. Among infants with all household contacts vaccinated, the effectiveness is estimated as 48.9% for ILI and 76.9% for SARI. Based on the results of multivariate logistic regression analysis, all-household vaccination is a protective factor against SARI (OR: 0.07 95% CI [0.01–0.56]), household size (OR: 1.75, 95% CI [1.24–2.48]) and presence of secondhand smoke (OR: 2.2, 95% CI [1.12–4.45]) significant risk factors for SARI in infants. The mother alone being vaccinated is not a statistically significant protective factor against ILI (OR: 0.46, 95% CI [0.19–1.18]) or SARI (OR: 0.3, 95% CI [0.11–1.21]). Along with the obtained results and analysis, this study provides clear evidence that influenza vaccination of all household contacts of infants aged 0–6 months is significantly associated with protecting infants from both ILI and SARI.

Environmental reservoirs of multidrug-resistant pseudomonads in a geographical location in Kenya with high community-acquired infections

Background Pseudomonads are gram negative bacteria and readily form biofilms in the environment, allowing long-term colonization and persistence in sinks, water systems. They pose a risk of life-threatening opportunistic infections in immune-compromised individuals. MDR strains, make treatment increasingly difficult. Environmentally persistent MDR strains are typically problematic within healthcare facilities, however, data on MDR pseudomonad reservoirs in settings with community-acquired infections to inform preventive interventions, in resource-constrained settings is scarce. Here, we determined reservoirs and antibiotic susceptibility of Pseudomonas species in water sources in Kisumu County, Kenya with reported high levels of community acquired pseudomonad infections. Methods We adopted a cross-sectional design, randomly collecting 297 samples from tap heads, sinks, tanks, vendor and household storage containers in six selected sub-locations and one hospital (KCRH). Standard microbiological procedures were used for identification and AST of the isolates. Results We isolated Pseudomonads from 14.1% of the samples collected, predominantly from the community 10.4%. Seven different pseudomonads were identified, with Pseudomonas aeruginosa predominating 6.7% overall, in the community samples 5.7%, and among isolates from water tanks 21.4%. Pseudomonad isolates were 62% non-susceptible to piperacillin, 57% to tigecycline, 24% meropenem, 21% cefepime, 19% levofloxacin and 14% colistin. Carbapenem resistance was mainly detected in P. aeruginosa 80% (8/10) from Milimani sub-location 75% (6/8). 45% of the isolates recovered were MDR, mainly community-associated carbapenem-resistant P. aeruginosa (CRPA) 42%, strains susceptible to colistin. The MDR pseudomonads exhibited high multiple antibiotic resistance indices, ranging from 0.43 to 1. Conclusion This study reveals a higher prevalence of MDR pseudomonads, including CRPA strains in community water sources. These potential conduits of drug resistance present a critical public health threat, especially among immunocompromised. Regular cleaning of water storage facilities, water treatment and implementation of antimicrobial stewardship programs, are required to prevent a rise in AMR and eliminate the environmental reservoirs that put the vulnerable populations at risk.

Predictive modeling for identifying infection risk following spinal surgery: Optimizing patient management

Predictive modeling for identifying infection risk following spinal surgery: Optimizing patient management

Characteristics and rates of infection by HIV in people receiving non-occupational post-exposure prophylaxis (nPEP) against HIV

Introduction/objectivesThe use of non-occupational post-exposure prophylaxis (nPEP) emerges as a strategic intervention to reduce HIV infection risk following sexual encounters in our setting. Notwithstanding, there is a scarcity of contemporary...

PPI use increases risk of COVID-19 infections after two doses of COVID-19 vaccine

PPI use increases risk of COVID-19 infections after two doses of COVID-19 vaccine

Systematic review and meta-analysis of Biodegradable Temporizing Matrix application for complex wound reconstruction.

Biodegradable Temporizing Matrix (BTM) is a synthetic dermal template recently developed to reconstruct complex wounds. Current literature describes BTM outcomes in the presence of infection and other comorbidities but are limited by small sample sizes. The purpose of this systemic review and meta-analysis was to determine current breadth and success of BTM use for complex wound closure. Databases were searched to identify previously published studies describing BTM use in human wounds. Studies were excluded if conducted in vitro, using non-human animals, or for procedures irrelevant to wound care. Twenty-four studies met inclusion criteria, representing 202 patients. The most common injury treated with BTM was burns (68 cases, 33.7%) followed by acute surgical wounds (59 cases, 29.2%). The large majority of patients did not experience any post-operative infections (76.6%). Infected wounds were associated with a 7.5-day delay from BTM to grafting. Univariate regression analyses showed a negative association between time to BTM implantation and age, exposed muscle, and exposed tendon (p < 0.001). Ninety-two percent of patients received BTM implantation less than 2 weeks from admission. Eighty-four percent of patients had a greater than 95% BTM take. The median time to STSG was 34 days, and 92% of patients experienced a greater than 95% STSG survival. To our knowledge, this is the first reported systemic review on the application of BTM for wound reconstruction. According to the published data, BTM is versatile dermal template for complex wounds coverage with low risk of infection, high template take rate, and excellent autograft survival.

Antibiotic impregnated catheters and intrathecal antibiotics for CSF shunt infection prevention in children undergoing low-risk CSF shunt surgery

BackgroundCerebrospinal fluid (CSF) shunts allow children with hydrocephalus to survive and avoid brain injury (J Neurosurg 107:345-57, 2007; Childs Nerv Syst 12:192-9, 1996). The Hydrocephalus Clinical Research Network implemented non-randomized quality improvement protocols that were shown to decrease infection rates compared to pre-operative prophylactic intravenous antibiotics alone (standard care): initially with intrathecal (IT) antibiotics between 2007–2009 (J Neurosurg Pediatr 8:22-9, 2011), followed by antibiotic impregnated catheters (AIC) in 2012–2013 (J Neurosurg Pediatr 17:391-6, 2016). No large scale studies have compared infection prevention between the techniques in children. Our objectives were to compare the risk of infection following the use of IT antibiotics, AIC, and standard care during low-risk CSF shunt surgery (i.e., initial CSF shunt placement and revisions) in children.MethodsA retrospective observational cohort study at 6 tertiary care children’s hospitals was conducted using Pediatric Health Information System + (PHIS +) data augmented with manual chart review. The study population included children ≤ 18 years who underwent initial shunt placement between 01/2007 and 12/2012. Infection and subsequent CSF shunt surgery data were collected through 12/2015. Propensity score adjustment for regression analysis was developed based on site, procedure type, and year; surgeon was treated as a random effect.ResultsA total of 1723 children underwent initial shunt placement between 2007–2012, with 1371 subsequent shunt revisions and 138 shunt infections. Propensity adjusted regression demonstrated no statistically significant difference in odds of shunt infection between IT antibiotics (OR 1.22, 95% CI 0.82–1.81, p = 0.3) and AICs (OR 0.91, 95% CI 0.56–1.49, p = 0.7) compared to standard care.ConclusionIn a large, observational multicenter cohort, IT antibiotics and AICs do not confer a statistically significant risk reduction compared to standard care for pediatric patients undergoing low-risk (i.e., initial or revision) shunt surgeries.

Iron, haemochromatosis genotypes, and risk of infections: a cohort study of 142,188 general population individuals

It is unclear whether risk of infection is increased in individuals with hereditary haemochromatosis and in individuals with low or high plasma iron, transferrin saturation, or ferritin. Therefore, we tested whether high and low iron, transferrin saturation, and ferritin are associated with risk of infections observationally and genetically through HFE genotypes. We studied 142,188 Danish general population individuals. Iron, transferrin saturation, and ferritin were measured in 136,656, 136,599, and 38,020 individuals, respectively. HFE was genotyped for C282Y and H63D in 132,542 individuals. Median follow-up after study enrolment was 8 years(range:0-38years) for hospital and emergency room admissions with infections(n=20,394 individuals) using the National Patient Register, covering all Danish hospitals. Hazard ratios for any infection were 1.20(95%CI:1.12-1.28) and 1.14(1.07-1.22) in individuals with plasma iron≤5th or ≥95th percentile compared to individuals with iron from 26th-74th percentiles. Findings for transferrin saturation were similar, while infection risk was not increased in individuals with ferritin≤5th or ≥95th percentile. Hazard ratios in C282Y homozygotes versus non-carriers were 1.40(1.16-1.68) for any infection, 1.69(1.05-2.73) for sepsis, and 2.34(1.41-3.90) for death from infectious disease. Risk of infection was increased in C282Y homozygotes with normal plasma iron, transferrin saturation, or ferritin, and in C282Y homozygotes without liver disease, diabetes, and/or heart failure. In summary, low and high plasma iron and transferrin saturation were independently associated with increased infection risk. C282Y homozygotes had increased risk of any infection, sepsis, and death from infections. Even C282Y homozygotes with normal iron, transferrin saturation, or ferritin, not currently recommended for genotyping, had increased infection risk.