Early Antibiotic Research Articles

Incidence of central venous and Foley’s catheter related bacteraemia, organisms responsible and antibiotic sensitivity pattern: in cardio-thoracic intensive theraputic unit following elective surgery, in a tertiary care hospital of Kolkata, India

Background: Mortality from bacteraemia related to indwelling Central Venous Pressure (CVP) lines could be as high as 12 - 25% and that due to indwelling urinary catheters about 5%, in critically ill patients. Hence, initiation of early and aggressive antibiotic therapy, often even before the culture- sensitivity reports are available is necessary. Objectives of the study was to find out the incidence of bacteraemia related to indwelling CVP catheters &/or Foley’s catheters in post operative patients in Cardio-thoracic Intensive Theraputic Unit (ITU) and to understand the antibiotic sensitivity patterns against the organisms causing such bacteraemiaMethods: 48 hours after their insertion, CVP catheter tips, Foley’s catheter tips and Peripheral blood samples were collected for cultures in 50 patients who underwent elective cardiothoracic surgery, over a period of one year and results were interpreted.Results: Incidence of bacteraemia associated with indwelling CVP catheters was 8% and was caused by both - Gram positive (Staphylococcus aureus, Enterococcus faecium) and Gram negative (Acinetobacter baumanii, Pseudomonas aeruginosa) organisms. Foley’s catheter was not related to such blood stream infection. Vancomycin and Linezolid were effective against the Gram positive organisms; while Piperacillin- Tazobactam, Meropenem, Polymyxin B and Colistin were effective against the Gram negative organisms.Conclusions: Indwelling CVP catheters were associated with blood stream infection in 4 post operative patients in our ITU. An idea about the organisms responsible, as well as their antibiogram may help in early initiation of antibiotics empirically before culture-sensitivity reports are available.

Impact of Early-Onset Sepsis and Antibiotic Use on Death or Survival with Neurodevelopmental Impairment at 2 Years of Age among Extremely Preterm Infants

To evaluate the hypothesis that early-onset sepsis increases risk of death or neurodevelopmental impairment (NDI) among preterm infants; and that among infants without early-onset sepsis, prolonged early antibiotics alters risk of death/NDI. Retrospective cohort study of infants born at the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network centers (2006-2014) at 22-26weeks of gestation andbirth weight 401-1000g. Early-onset sepsis defined as growth of a pathogen from blood or cerebrospinal fluidculture ≤72hours after birth. Prolonged early antibiotics was defined as antibiotics initiated ≤72hours and continued ≥5days without culture-confirmed infection, necrotizing enterocolitis, or spontaneous perforation. Primary outcome was death before follow-up or NDI assessed at 18-26months corrected age. Poisson regression was used to estimate adjusted relative risk (aRR) and CI for early-onset sepsis outcomes. A propensity score for receiving prolonged antibiotics was derived from early clinical factors and used to match infants (1:1) with and without prolonged antibiotic exposure. Log binomial models were used to estimate aRR for outcomes in matched infants. Among 6565 infants, those with early-onset sepsis had higher aRR (95% CI) for death/NDI compared with infants managed with prolonged antibiotics (1.18 [1.06-1.32]) and to infants without prolonged antibiotics (1.23 [1.10-1.37]). Propensity score matching was achieved for 4362 infants. No significant difference in death/NDI (1.04 [0.98-1.11]) was observed with or without prolonged antibiotics among the matched cohort. Early-onset sepsis was associated with increased risk of death/NDI among extremely preterm infants. Among matched infants without culture-confirmed infection, prolonged early antibiotic administration was not associated with death/NDI.

Impact of Prehospital Antibiotic Therapy on Septic Shock Mortality

Background Septic shock (SS) is associated with high morbidity and mortality rate. Early antibiotic therapy administration in septic patients was shown to reduce mortality but its impact on mortality in a prehospital setting is still under debate. To clarify this point, we performed a retrospective analysis on patients with septic shock who received antibiotics in a prehospital setting. Methods From April 15th, 2017 to March 1st, 2020, patients with septic shock requiring Mobile Intensive Care Unit (MICU) intervention were retrospectively analyzed to assess the impact of prehospital antibiotic therapy administration on a 30-day mortality. Results Three-hundred-eight patients with septic shock requiring MICU intervention in the prehospital setting were analyzed. The mean age of the study population was 70 ± 15 years. Presumed origin of SS was mainly pulmonary (44%), digestive (21%) or urinary (19%) infection. Overall 30-day mortality was 29%. Ninety-eight (32%) patients received antibiotic therapy. Using Cox regression analysis, we showed that prehospital antibiotic therapy significantly reduces 30-day mortality for patients with septic shock (hazard ratio = 0.56, 95%CI [0.35-0.89], p = 0.016). Conclusion In this retrospective study, prehospital antibiotic therapy reduces 30-day mortality of septic shock patients cared for by MICU. Further studies will be needed to confirm the beneficial effect of prehospital antibiotic therapy in association or not with prehospital hemodynamic optimization to improve the survival of septic shock patients.

Sepsis and Septic Shock in Low- and Middle-Income Countries.

Background: The greatest burden of sepsis- and septic shock-related morbidity and mortality is in low- and middle-income countries (LMICs). Accurate tracking of incidence and outcomes of patients in LMICs with sepsis has been limited by changing definitions, lack of diagnosis coding and health records, and deficits in personnel. Improving sepsis care in LMICs requires studying outcomes prospectively so that setting appropriate definitions, scoring systems, and treatment guidelines can be created. Our goal is to review the burden of sepsis and septic shock in LMICs, the evolution and applicability of definitions to LMICs, and management. Methods: The literature was searched through PubMed using a Boolean approach and the following terms: sepsis, septic shock, low- and middle-income countries. Articles were read by the authors and relevant information was abstracted and included with citations to create a narrative review. Results: The estimated worldwide incidence of sepsis admissions is 31.5 million cases per year leading to 5.3 million deaths. The World Health Organization (WHO) has urged LMICs to establish sepsis prevalence and outcomes. Most authors and societies involved in creating sepsis and septic shock definitions have been from high-income countries (HICs). Applicability of sepsis definitions in LMICs is uncertain. Quick-Sequential Organ Failure Assessment (qSOFA) and universal vital assessment (UVA) are useful screening and triage tools in LMICs because they can be done at the bedside. The key tenets of management of sepsis and septic shock in LMICs include early fluid resuscitation and antibiotic therapy coupled with source control when there is a surgical process. Surgical causes of sepsis should be identified rapidly. Scaling up surgical capacity in LMICs is an important step to improve source control of sepsis. Conclusion: Management guidelines specific to LMICs for sepsis and septic shock need to be refined further and studied prospectively. Improving access to surgery will improve outcomes of surgical cases of sepsis.

Local Application of a Gentamicin-Loaded Hydrogel Early After Injury Is Superior to Perioperative Systemic Prophylaxis in a Rabbit Open Fracture Model.

Open fractures are at significant risk of developing a fracture-related infection, despite the routine administration of perioperative antibiotic prophylaxis. Early application of antibiotic prophylaxis is known to reduce infection rates; however, most international guidelines focus on postoperative duration rather than prehospital administration. We compared conventional perioperative prophylaxis against early prehospital prophylaxis either as a systemic single shot of cefuroxime or a locally applied gentamicin-loaded hydrogel in a laboratory animal model. Thirty New Zealand white rabbits underwent a first surgical procedure to create an open wound, bone damage and contamination with Staphylococcus aureus. After a 4-hour observation period mimicking the time-to-treatment, the animals underwent a second procedure to irrigate the wound and apply a fracture fixation device. The 5 groups (n = 6 per group) received (1) no treatment; (2) conventional 24-hour cefuroxime; (3) an early single shot of cefuroxime 15 minutes after trauma; (4) a combined early and standard systemic prophylaxis; and (5) early application of a gentamicin-loaded hydrogel that was removed during irrigation. Untreated animals displayed high numbers of bacteria in irrigation fluid and were all highly culture positive at euthanasia. Three of 6 animals were culture positive at euthanasia after conventional prophylaxis. Early systemic prophylaxis reduced bacterial burden in irrigation fluid by up to 100-fold, but 5/6 animals were culture positive at euthanasia. The combined prophylaxis displayed greater efficacy with only 1/6 rabbits culture positive at euthanasia. Local application of the gentamicin-loaded hydrogel reduced bacteria recovered by irrigation to just above our detection limit, and at euthanasia, all animals were culture negative at euthanasia. Early systemic antibiotic administration can significantly reduce bacterial burden in the operative field and reduce culture positivity at euthanasia when continued for 24 hours after injury. The early application of a gentamicin-loaded hydrogel that was removed during irrigation displayed superior efficacy to early systemic therapy alone and postoperative conventional gold standard 24-hour systemic therapy alone. These experimental results highlight the importance of early antibiotic administration in fracture care.

Putting the microbiota to work: Epigenetic effects of early life antibiotic treatment are associated with immune-related pathways and reduced epithelial necrosis following Salmonella Typhimurium challenge in vitro.

Salmonella enterica serovar Typhimurium is an animal welfare and public health concern due to its ability to parasite livestock and potentially contaminate pork products. To reduce Salmonella shedding and the risk of pork contamination, antibiotic therapy is used and can contribute to antimicrobial resistance. Here we hypothesized that immune system education by the microbiota can play a role in intestinal resilience to infection. We used amoxicillin (15mg/Kg) to modulate the intestinal microbiome of 10 piglets, paired with same age pigs that received a placebo (n = 10) from 0 to 14 days of age. Animals were euthanized at 4-weeks old. Each pig donated colon sections for ex vivo culture (n = 20 explants/pig). Explants were inoculated with S. Typhimurium, PBS or LPS (n = 6 explants/pig/group, plus technical controls). The gut bacteriome was characterized by sequencing of the 16S rRNA at 7, 21 days of age, and upon in vitro culture. Explants response to infection was profiled through high-throughput mRNA sequencing. In vivo antibiotic treatment led to β-diversity differences between groups at all times (P<0.05), while α-diversity did not differ between amoxicillin and placebo groups on day 21 and at euthanasia (P<0.03 on day 7). Explant microbiomes were not different from in vivo. In vitro challenge with S. Typhimurium led to lower necrosis scores in explants from amoxicillin-treated pigs, when compared to explants placebo-treated pigs (P<0.05). This was coupled with the activation of immune-related pathways in explants from amoxicillin-treated pigs (IL-2 production, NO production, BCR activation), when compared to placebo-treated pigs. In addition, several DNA repair and intestinal wound healing pathways were also only activated in explants from amoxicillin-treated pigs. Taken together, these findings suggest that immune education by the amoxicillin-disturbed microbiota may have contributed to mitigate intestinal lesions following pathogen exposure.

Implication of gut microbiota in the association between infant antibiotic exposure and childhood obesity and adiposity accumulation.

In animal studies early life antibiotic exposure causes metabolic abnormalities including obesity through microbiota disruption, but evidence from human studies is scarce. We examined involvement of gut microbiota in the associations between infant antibiotic exposure and childhood adiposity. Infant antibiotic exposure in the first year of life was ascertained using parental reports during interviewer-administered questionnaires. Primary outcomes were childhood obesity [body mass index (BMI) z-score > 95th percentile] and adiposity [abdominal circumference (AC) and skinfold (triceps + subscapular (SST)) measurements] determined from ages 15-60 months. At age 24 months, when the gut microbiota are more stable, stool samples (n = 392) were collected for the gut microbiota profiling using co-abundancy networks. Associations of antibiotic exposure with obesity and adiposity (n = 1016) were assessed using multiple logistic and linear mixed effects regressions. Key bacteria associated with antibiotics exposure were identified by partial redundancy analysis and multivariate association with linear models. Antibiotic exposure was reported in 38% of study infants. In a fully adjusted model, a higher odds of obesity from 15-60 months of age was observed for any antibiotic exposure [OR(95% CI) = 1.45(1.001, 2.14)] and exposure to ≥3 courses of antibiotics [2.78(1.12, 6.87)]. For continuous adiposity indicators, any antibiotic exposure was associated with higher BMI z-score in boys [β = 0.15(0.01, 0.28)] but not girls [β = -0.04(-0.19, 0.11)] (P interaction = 0.026). Similarly, exposure to ≥3 courses of antibiotics was associated with higher AC in boys [1.15(0.05, 2.26) cm] but not girls [0.57(-1.32, 2.45) cm] (P interaction not significant). Repeated exposure to antibiotics was associated with a significant reduction (FDR-corrected P values < 0.05) in a microbial co-abundant group (CAG) represented by Eubacterium hallii, whose proportion was negatively correlated with childhood adiposity. Meanwhile, a CAG represented by Tyzzerella 4 was positively correlated with the repeated use of antibiotics and childhood adiposity. Infant antibiotic exposure was associated with disruption of the gut microbiota and the higher risks of childhood obesity and increased adiposity.

Potential Impact of Umbilical-Cord-Blood Procalcitonin-Based Algorithm on Antibiotics Exposure in Neonates With Suspected Early-Onset Sepsis

Context: The incidence of early-onset neonatal infection has greatly decreased, but a new diagnostic approach is needed to avoid overdiagnosis and overtreatment. The aim of this study was to assess the potential impact of an algorithm incorporating umbilical-cord-blood procalcitonin (PCT) level on neonatal antibiotics prescription rate as compared with current practice.Material and methods: We conducted a prospective study in three maternity wards in France. All term and preterm neonates with the usual risk factors for neonatal group B Streptococcus infection were eligible for umbilical-cord-blood PCT testing. We compared the proportion of neonates who were exposed early to antibiotics (before 6 days of life) to that of neonates for whom antibiotics prescription would be indicated according to the PCT-based algorithm.Results: Among the 3,080 neonates included, 1 neonate presented with certain infection and 38 neonates with probable infection. The global antibiotics prescription rate was 4.6% [95% confidence interval (CI), 4.1–5]. With the PCT-based algorithm, the potential decrease in prescription rate would be 1.8% (95% CI, 1.3–2.3), corresponding to a 39% (95% CI, 37.3–40.7) relative reduction in antibiotics exposure (p < 0.05).Conclusion: These results suggest that the umbilical-cord-blood PCT-based algorithm could significantly help the clinicians in their antibiotic prescription decision to decrease neonatal antibiotics exposure as compared with current practice. If validated in a larger interventional randomized study, this approach could help clinicians stratify the risk of early-onset neonatal infection and initiate early antibiotics treatment in newborns at high risk of infection while limiting the deleterious effects of useless prescriptions in non-infected newborns.

Early and Short-Term Interventions in the Gut Microbiota Affects Lupus Severity, Progression, and Treatment in MRL/lpr Mice.

There have been attempts to reveal the possible associations between systemic lupus erythematosus (SLE) and gut microbiota. Using MRL/lpr mice, this study was performed to reveal whether early and short-term interventions in gut microbiota affect lupus. MRL/lpr mice were treated with antibiotics or fecal microbiota transplantation (FMT) before onset. Then, prednisone was used to treat the lupus mice with initially different gut microbiota compositions. The compositions of gut microbiota were assessed by the V3-V4 region of 16S rRNA gene sequence. Early and short-term antibiotics exposure aggravated lupus severity by depleting beneficial gut microbiota for lupus, such as Lactobacillus and Bifidobacterium, and enriching harmful gut microbiota for lupus, such as Klebsiella and Proteus. FMT alleviated lupus severity by renovating the antibiotic-induced dysbiosis of gut microbiota in the following 1 week after antibiotics exposure. Besides, short-term antibiotics exposure before onset imposed no significant effects on lupus progression, but the following one week of FMT suppressed lupus progression. Moreover, the short-term antibiotics or FMT before onset inhibited the therapeutic efficiency of prednisone on lupus from 9 to 13 weeks old of MRL/lpr mice. These data demonstrate that the gut microbiota before onset is important for lupus severity, progression and treatment.

How rare is isolated rheumatic tricuspid valve disease?

The incidence of rheumatic fever (RF) has markedly decreased in Europe since the beginning of the 20th century due to improved living conditions, early antibiotic therapy in streptococcal pharyngitis, and changes in serotypes of circulating streptococci. Isolated outbreaks of RF are still found in various parts of the world and the disease has changed its presentation with milder joint symptoms and subclinical carditis that make the correct diagnosis more difficult. Patients can present many years later with severe valve disease and significant disability. This article presents a case of isolated rheumatic tricuspid valve disease that presented with signs and symptoms of right heart failure and severe valve damage. Isolated involvement of the tricuspid valve is rarely found in rheumatic fever and a thorough differential diagnosis is needed.

A Study to Determine the Role of Early Vitrectomy vs Intravitreal Antibiotics in Patients with Postoperative Endophthalmitis

A Study to Determine the Role of Early Vitrectomy vs Intravitreal Antibiotics in Patients with Postoperative Endophthalmitis

The anatomical site of perforation peritonitis and their microbiological profile: a cross-sectional study

Background: Initiation of early appropriate antibiotic therapy influences the outcome of perforation peritonitis, which otherwise is delayed till culture reports are available. The knowledge of microbial profile and sensitivity of peritoneal fluid culture with respect to the anatomical site of perforation peritonitis will help in initiation of early appropriate antibiotic therapy in the post-operative period.Methods: A cross-sectional study conducted from January 2017 to December 2017 where intraoperative peritoneal fluid sample in patients of perforation peritonitis was subjected to culture (aerobic and anaerobic) and sensitivity and results analysed with respect to anatomical site of perforation.Results: 50 patients were studied. The most common site of perforation was ileum (32%) followed by appendix (18%) and stomach (18%). In aerobic culture, the culture positivity rate was highest in colonic perforation (100%) and least in gastric perforation (44.4%). The most common organism isolated in all sites of perforation peritonitis was E. coli followed by Klebsiella spp. In anaerobic culture, although facultative anaerobes were isolated, no strict anaerobe was isolated. The most sensitive antibiotics covering all isolated organisms were gentamycin (p=0.006), colistin (p=0.018), piperacillin and tazobactum (p=0.022).Conclusions: The predominant differential normal flora according to site of gastrointestinal tract was not reflected in the peritoneal fluid culture of patients with perforation peritonitis and E. coli was the most common organism isolated in all sites of perforation peritonitis. The antibiotic sensitivity profile showed the increasing resistance against third generation cephalosporins. Aminoglycosides, piperacillin and tazobactum, meropenem and colistin showed a significant antimicrobial activity against organisms isolated from cases of perforation peritonitis.

Short-Term Amoxicillin-Induced Perturbation of the Gut Microbiota Promotes Acute Intestinal Immune Regulation in Brown Norway Rats.

The intestinal gut microbiota is essential for maintaining host health. Concerns have been raised about the possible connection between antibiotic use, causing microbiota disturbances, and the increase in allergic and autoimmune diseases observed during the last decades. To elucidate the putative connection between antibiotic use and immune regulation, we have assessed the effects of the antibiotic amoxicillin on immune regulation, protein uptake, and bacterial community structure in a Brown Norway rat model. Daily intra-gastric administration of amoxicillin resulted in an immediate and dramatic shift in fecal microbiota, characterized by a reduction of within sample (α) diversity, reduced variation between animals (β diversity), increased relative abundance of Bacteroidetes and Gammaproteobacteria, with concurrent reduction of Firmicutes, compared to a water control group. In the small intestine, amoxicillin also affected microbiota composition significantly, but in a different way than observed in feces. The small intestine of control animals was vastly dominated by Lactobacillus, but this genus was much less abundant in the amoxicillin group. Instead, multiple different genera expanded after amoxicillin administration, with high variation between individual animals, thus the small intestinal α and β diversity were higher in the amoxicillin group compared to controls. After 1 week of daily amoxicillin administration, total fecal IgA level, relative abundance of small intestinal regulatory T cells and goblet cell numbers were higher in the amoxicillin group compared to controls. Several bacterial genera, including Escherichia/Shigella, Klebsiella (Gammaproteobacteria), and Bifidobacterium, for which the relative abundance was higher in the small intestine in the amoxicillin group than in controls, were positively correlated with the fraction of small intestinal regulatory T cells. Despite of epidemiologic studies showing an association between early life antibiotic consumption and later prevalence of inflammatory bowel diseases and food allergies, our findings surprisingly indicated that amoxicillin-induced perturbation of the gut microbiota promotes acute immune regulation. We speculate that the observed increase in relative abundance of small intestinal regulatory T cells is partly mediated by immunomodulatory lipopolysaccharides derived from outgrowth of Gammaproteobacteria.

THE MICROBIAL PATTERN OF COMPLICATED INTRA-ABDOMINAL INFECTIONS COMMUNITY IN H. ADAM MALIK GENERAL HOSPITAL MEDAN

Introduction: The principles management of complicated intra-abdominal infections are source control and antibiotic therapy. The main problem in its implementation is the slow handling time and inadequate antibiotic therapy, which leads in an increase in mortality in complicated intra-abdominal infections. Early empirical antibiotics are based on the pathological location and community microbial pattern. This study is aimed to evaluate microbial pattern at H. Adam Malik General Hospital between January 2017 and October 2019. Methods: This is a retro-prospective observational descriptive study. Results: There were 37 patients who met the inclusion criteria. The most common microbial pattern in this study was gramnegative bacteria, which was 62.1%. The most common gram-negative bacteria found were E.coli (32.4%), followed by Klebsiella pneumonia (24.3%). While the most common gram-positive bacteria found was Staphylococcus haemolyticus (8.1%). Conclusion: The most common microbial pattern found in this study was gram-negative bacteria, where the most common gram-negative bacteria was E. coli. The most common gram-positive bacteria was Staphylococcus haemolyticus

Role of Prophylactic Antibiotics in Critical Care of Stroke Patients - A Preventive Approach to Post-stroke Infections?

Post-stroke complications are very common worldwide and the most common complication is infection. This contributes the most to the mortality rate in stroke patients. Among the infections, pneumonia and urinary tract infections are most common. Hyperthermia following stroke is associated with neuronal damage and worse outcomes. Post-stroke immunosuppression and activation of inflammatory mediators also cause infections. Based on the high mortality caused by post-stroke infections, various trials were done to seek the advantage that prophylactic antibiotics can give in the critical care of stroke patients. Antibiotics, including ceftriaxone (cephalosporin), levofloxacin (fluoroquinolone), penicillin, and minocycline (tetracycline), were used and the stroke patients were followed up to analyze the primary and secondary outcomes. It was concluded that early antibiotic therapy (mostly within 24 hours) leads to a reduced rate of post-stroke infections and reduced fever spikes, whereas follow-up for a longer period of time showed no better functional outcome. Furthermore, mortality and morbidity benefits were also not seen with prophylactic antibiotic therapy. This review helped us to put a nail in the coffin to the earlier thoughts that prophylactic antibiotics are necessary for the critical care of stroke patients.

Surgical timing for open fractures

Controversy exists over the optimal management of open fractures as new clinical studies question open fracture management dogma. Open fractures are complex injuries requiring the orthopaedic surgeon to consider both the bone injury as well as associated soft tissue injury. Early intravenous antibiotics and tetanus prophylaxis remain instrumental in infection prevention. However, the “six-hour rule” for initial open fracture debridement and revascularization has come into question. New evidence supports initial debridement within 24 hours with the appropriate surgical team. Additionally, orthopaedic surgeons and vascular surgeons should collaborate on the sequence of management of open fractures with associated vascular injury. Whereas debates on the optimal irrigation pressure and solution have been answered by multicenter randomized controlled trials, further research is required to determine the optimal irrigation volume and timing of wound closure. With advances in management of open fractures, the utility of well-known classification systems including the Gustilo-Anderson classification and Mangled Extremity Severity Score need to be re-evaluated in favor of up-to-date classification systems which better guide management and predict prognosis.

Combinations of early generation antibiotics and antimicrobial peptides are effective against a broad spectrum of bacterial biothreat agents

The misuse of infectious disease pathogens as agents of deliberate attack on civilians and military personnel is a serious national security concern, which is exacerbated by the emergence of natural or genetically engineered multidrug resistant strains. In this study, the therapeutic potential of combinations of an antibiotic and a broad-spectrum antimicrobial peptide (AMP) was evaluated against five bacterial biothreats, the etiologic agents of glanders (Burkholderia mallei), melioidosis (Burkholderia pseudomallei), plague (Yersinia pestis), tularemia (Francisella tularensis), and anthrax (Bacillus anthracis). The therapeutics included licensed early generation antibiotics which are now rarely used. Three antibiotics and one 24- amino acid AMP were selected based on MIC assay data. Combinations of the AMP and tigecycline, minocycline, or novobiocin were screened for synergistic activity by checkerboard MIC assay. The combinations each enhanced the susceptibility of several strains. The tetracycline-peptide combinations increased the sensitivities of Y. pestis, F. tularensis, B. anthracis and B. pseudomallei, and the novobiocin-AMP combination augmented the sensitivity of all five. In time-kill assays, down-selected combinations of the peptide and minocycline or tigecycline enhanced killing of B. anthracis, Y. pestis, F. tularensis, and Burkholderia mallei but not B. pseudomallei. The novobiocin-AMP pair significantly reduced viability of all strains except B. mallei, which was very sensitive to the antibiotic alone. The results suggested that antibiotic-AMP combinations are useful tools for combating diverse pathogens. Future studies employing cell culture and animal models will utilize virulent strains of the agents to investigate the in vivo availability, host cytotoxicity, and protective efficacy of these therapeutics.

Neonatal microbiota development and the effect of early life antibiotics are determined by two distinct settler types

The neonatal period, during which the initial gut microbiota is acquired, is a critical phase. The healthy development of the infant’s microbiome can be interrupted by external perturbations, like antibiotics, which are associated with profound effects on the gut microbiome and various disorders later in life. The aim of this study was to investigate the development of intestinal microbiota and the effect of antibiotic exposure during the first three months of life in term infants. Fecal samples were collected from healthy infants and infants who received antibiotics in the first week of life at one week, one month, and three months after birth. Microbial composition was analyzed using IS-pro and compared between antibiotics-treated and untreated infants. In total, 98 infants, divided into four groups based on feeding type and delivery mode, were analyzed. At one week of age, samples clustered into two distinct groups, which were termed “settler types”, based on their Bacteroidetes abundance. Caesarean-born infants belonged to the low-Bacteroidetes settler type, but vaginally-born infants were divided between the two groups. The antibiotics effect was assessed within a subgroup of 45 infants, vaginally-born and exclusively breastfed, to minimize the effect of other confounders. Antibiotics administration resulted in lower Bacteroidetes diversity and/or a delay in Bacteroidetes colonization, which persisted for three months, and in a differential development of the microbiota. Antibiotics resulted in pronounced effects on the Bacteroidetes composition and dynamics. Finally, we hypothesize that stratification of children’s cohorts based on settler types may reveal group effects that might otherwise be masked.

Antibiotics &amp; adjuvant corticosteroids in management of pneumococcal meningitis: a retrospective case-notes audit

Background Pneumococcus remains the most common cause of bacterial meningitis with high morbidity and mortality. Adjuvant corticosteroids with early antibiotics have been shown to reduce the neurological morbidity and mortality respectively and this is reflected in British Infection Society (BIS) guidance. Aim To assess how closely BIS guidelines were followed regarding antibiotic and adjuvant corticosteroid administration in management of pneumococcal meningitis. Methods Newcastle Upon Tyne Hospital case-notes of pneumococcal meningitis from a 7-year-period(2012-2019) were audited. Patients were identified using microbiological records and case-notes. Data was collected on intervals from initial-assessment to commencing antibiotics and corticosteroids. Results Eighteen cases were identified of whom three(17%) presented with the classic triad (fever, meningism, reduced GCS). All patients received appropriate antibiotics: 3/18(17%) within first hour of assessment. The median time to antibiotics was 5h 8mins (range:21-7129min). Eight patients(44%) received antibiotics &gt;6h after assessment. Twelve patients(67%) received corticosteroids; only six(33%) at the recommended dose and duration. Mean time from antibiotics to corticosteroids was 6h1min. Five deaths occurred in the cohort with three attributable to pneumococcal sepsis (all had late presentations). 6/18 had significant neurological sequelae, irrespective of whether they received corticosteroids. Discussion The significant morbidity and mortality of pneumococcal meningitis demands a high index of suspicion. BIS guideline targets are repeatedly not met; long delays exist between assessment and antibiotic and corticosteroid administration. Integrated electronic prescribing and clinical Early Warning Systems have potential to ameliorate this with meningitis-tailored order sets to prompt consideration of meningitis and guide correct prescribing.

Care of the patient with invasive meningococcal disease by prehospital emergency medical service clinicians: a scoping review

ObjectiveThe objective of this scoping review is to systematically map the literature to identify the scope, depth, key concepts and gaps in the evidence regarding care of the patient with...