scholarly journals rpoS-Regulated Core Genes Involved in the Competitive Fitness of Salmonella enterica Serovar Kentucky in the Intestines of Chickens

2014 ◽  
Vol 81 (2) ◽  
pp. 502-514 ◽  
Author(s):  
Ying Cheng ◽  
Adriana Ayres Pedroso ◽  
Steffen Porwollik ◽  
Michael McClelland ◽  
Margie D. Lee ◽  
...  
Keyword(s):  
United States ◽  
Salmonella Enterica ◽  
The United States ◽  
Differential Regulation ◽  
Metabolic Adaptation ◽  
Content Type ◽  
Metabolic Genes ◽  
Core Genes

ABSTRACTSalmonella entericaserovar Kentucky has become the most frequently isolated serovar from poultry in the United States over the past decade. Despite its prevalence in poultry, it causes few human illnesses in the United States. The dominance ofS. Kentucky in poultry does not appear to be due to single introduction of a clonal strain, and its reduced virulence appears to correlate with the absence of virulence genesgrvA,sseI,sopE, andsodC1. S. Kentucky's prevalence in poultry is possibly attributable to its metabolic adaptation to the chicken cecum. While there were no difference in the growth rate ofS. Kentucky andS. Typhimurium grown microaerophilically in cecal contents,S. Kentucky persisted longer when chickens were coinfected withS. Typhimurium. Thein vivoadvantage thatS. Kentucky has overS. Typhimurium appears to be due to differential regulation of coreSalmonellagenes via the stationary-phase sigma factorrpoS. Microarray analysis ofSalmonellagrown in cecal contentsin vitroidentified several metabolic genes and motility and adherence genes that are differentially activated inS. Kentucky. The contributions of four of these operons (mgl,prp,nar, andcsg) toSalmonellacolonization in chickens were assessed. Deletion ofmglandcsgreducedS. Kentucky persistence in competition studies in chickens infected with wild-type or mutant strains. Subtle mutations affecting differential regulation of coreSalmonellagenes appear to be important inSalmonella's adaptation to its animal host and especially forS. Kentucky's emergence as the dominant serovar in poultry.

scholarly journals USA300 and USA500 Clonal Lineages of Staphylococcus aureus Do Not Produce a Capsular Polysaccharide Due to Conserved Mutations in the cap5 Locus

mBio ◽  
2015 ◽  
Vol 6 (2) ◽  
Author(s):  
Susan Boyle-Vavra ◽  
Xue Li ◽  
Md Tauqeer Alam ◽  
Timothy D. Read ◽  
Julia Sieth ◽  
...  
Keyword(s):  
United States ◽  
Staphylococcus Aureus ◽  
Capsular Polysaccharide ◽  
The United States ◽  
Whole Genome Sequence ◽  
Content Type ◽  
Capsule Production ◽  
Usa300 Strain

ABSTRACTThe surface capsular polysaccharide (CP) is a virulence factor that has been used as an antigen in several successful vaccines against bacterial pathogens. A vaccine has not yet been licensed againstStaphylococcus aureus, although two multicomponent vaccines that contain CP antigens are in clinical trials. In this study, we evaluated CP production in USA300 methicillin-resistantS. aureus(MRSA) isolates that have become the predominant community-associated MRSA clones in the United States. We found that all 167 USA300 MRSA and 50 USA300 methicillin-susceptibleS. aureus(MSSA) isolates were CP negative (CP−). Moreover, all 16 USA500 isolates, which have been postulated to be the progenitor lineage of USA300, were also CP−. Whole-genome sequence analysis of 146 CP−USA300 MRSA isolates revealed they all carry acap5locus with 4 conserved mutations compared with strain Newman. Genetic complementation experiments revealed that three of these mutations (in thecap5promoter,cap5Dnucleotide 994, andcap5Enucleotide 223) ablated CP production in USA300 and that Cap5E75 Asp, located in the coenzyme-binding domain, is essential for capsule production. All but three USA300 MSSA isolates had the same fourcap5mutations found in USA300 MRSA isolates. Most isolates with a USA500 pulsotype carried three of these four USA300-specific mutations, suggesting the fourth mutation occurred in the USA300 lineage. Phylogenetic analysis of thecaploci of our USA300 isolates as well as publicly available genomes from 41 other sequence types revealed that the USA300-specificcap5mutations arose sequentially inS. aureusin a common ancestor of USA300 and USA500 isolates.IMPORTANCEThe USA300 MRSA clone emerged as a community-associated pathogen in the United States nearly 20 years ago. Since then, it has rapidly disseminated and now causes health care-associated infections. This study shows that the CP-negative (CP−) phenotype has persisted among USA300 isolates and is a universal and characteristic trait of this highly successful MRSA lineage. It is important to note that a vaccine consisting solely of CP antigens would not likely demonstrate high efficacy in the U.S. population, where about half of MRSA isolates comprise USA300. Moreover, conversion of a USA300 strain to a CP-positive (CP+) phenotype is unlikelyin vivoorin vitrosince it would require the reversion of 3 mutations. We have also established that USA300 MSSA isolates and USA500 isolates are CP−and provide new insight into the evolution of the USA300 and USA500 lineages.

scholarly journals Antimicrobial Susceptibility to Azithromycin among Salmonella enterica Isolates from the United States

2011 ◽  
Vol 55 (9) ◽  
pp. 3985-3989 ◽  
Author(s):  
Maria Sjölund-Karlsson ◽  
Kevin Joyce ◽  
Karen Blickenstaff ◽  
Takiyah Ball ◽  
Jovita Haro ◽  
...  
Keyword(s):  
United States ◽  
Antimicrobial Susceptibility ◽  
Salmonella Enterica ◽  
Antimicrobial Agents ◽  
The United States ◽  
Outcome Data ◽  
Content Type ◽  
Susceptibility Data ◽  
Retail Meat ◽  
Clinical Breakpoints

ABSTRACTDue to emerging resistance to traditional antimicrobial agents, such as ampicillin, trimethoprim-sulfamethoxazole, and chloramphenicol, azithromycin is increasingly used for the treatment of invasiveSalmonellainfections. In the present study, 696 isolates of non-TyphiSalmonellacollected from humans, food animals, and retail meats in the United States were investigated for antimicrobial susceptibility to azithromycin. Seventy-twoSalmonella entericaserotype Typhi isolates from humans were also tested. For each isolate, MICs of azithromycin and 15 other antimicrobial agents were determined by broth microdilution. Among the non-TyphiSalmonellaisolates, azithromycin MICs among human isolates ranged from 1 to 32 μg/ml, whereas the MICs among the animal and retail meat isolates ranged from 2 to 16 μg/ml and 4 to 16 μg/ml, respectively. AmongSalmonellaserotype Typhi isolates, the azithromycin MICs ranged from 4 to 16 μg/ml. The highest MIC observed in the present study was 32 μg/ml, and it was detected in three human isolates belonging to serotypes Kentucky, Montevideo, and Paratyphi A. Based on our findings, we propose an epidemiological cutoff value (ECOFF) for wild-typeSalmonellaof ≤16 μg/ml of azithromycin. The susceptibility data provided could be used in combination with clinical outcome data to determine tentative clinical breakpoints for azithromycin andSalmonella enterica.

scholarly journals Terminal Deoxynucleotidyl Transferase Is Not Required for Antibody Response to Polysaccharide Vaccines againstStreptococcus pneumoniaeandSalmonella entericaSerovar Typhi

2018 ◽  
Vol 86 (9) ◽  
Author(s):  
Vivek Belde ◽  
Matthew P. Cravens ◽  
Dania Gulandijany ◽  
Justin A. Walker ◽  
Isabel Palomo-Caturla ◽  
...  
Keyword(s):  
Antibody Response ◽  
B Cell ◽  
Salmonella Enterica ◽  
Passive Immunization ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Human Infants ◽  
Content Type ◽  
Serovar Typhimurium

ABSTRACTB cell antigen receptor (BCR) diversity increases by several orders of magnitude due to the action of terminal deoxynucleotidyl transferase (TdT) during V(D)J recombination. Unlike adults, infants have limited BCR diversity, in part due to reduced expression of TdT. Since human infants and young mice respond poorly to polysaccharide vaccines, such as the pneumococcal polysaccharide vaccine Pneumovax23 and Vi polysaccharide (ViPS) ofSalmonella entericaserovar Typhi, we tested the contribution of TdT-mediated BCR diversity in response to these vaccines. We found that TdT+/−and TdT−/−mice generated comparable antibody responses to Pneumovax23 and survivedStreptococcus pneumoniaechallenge. Moreover, passive immunization of B cell-deficient mice with serum from Pneumovax23-immunized TdT+/−or TdT−/−mice conferred protection. TdT+/−and TdT−/−mice generated comparable levels of anti-ViPS antibodies and antibody-dependent, complement-mediated bactericidal activity againstS. Typhiin vitro. To test the protective immunity conferred by ViPS immunizationin vivo, TdT+/−and TdT−/−mice were challenged with a chimericSalmonella entericaserovar Typhimurium strain expressing ViPS, since mice are nonpermissive hosts forS. Typhi infection. Compared to their unimmunized counterparts, immunized TdT+/−and TdT−/−mice challenged with ViPS-expressingS. Typhimurium exhibited a significant reduction in the bacterial burden and liver pathology. These data suggest that the impaired antibody response to the Pneumovax23 and ViPS vaccines in the young is not due to limited TdT-mediated BCR diversification.

scholarly journals Increased Resistance to Multiple Antimicrobials and Altered Resistance Gene Expression in CMY-2-Positive Salmonella enterica following a Simulated Patient Treatment with Ceftriaxone

2012 ◽  
Vol 78 (22) ◽  
pp. 8062-8066 ◽  
Author(s):  
Russell D. Hamilton ◽  
Holly J. Hulsebus ◽  
Samina Akbar ◽  
Jeffrey T. Gray
Keyword(s):  
Gene Expression ◽  
Antimicrobial Resistance ◽  
Resistance Gene ◽  
Resistance Genes ◽  
Salmonella Enterica ◽  
The United States ◽  
Simulated Patient ◽  
Patient Treatment ◽  
Content Type

ABSTRACTSalmonellosis is one of the most common causes of food-borne disease in the United States. Increasing antimicrobial resistance and corresponding increases in virulence present serious challenges. Currently, empirical therapy for invasiveSalmonella entericainfection includes either ceftriaxone or ciprofloxacin (E. L. Hohmann, Clin. Infect. Dis. 32:263–269, 2001). TheblaCMY-2gene confers resistance to ceftriaxone, the antimicrobial of choice for pediatric patients with invasiveSalmonella entericainfections, making these infections especially dangerous (J. M. Whichard et al., Emerg. Infect. Dis. 11:1464–1466, 2005). We hypothesized thatblaCMY-2-positiveSalmonella entericawould exhibit increased MICs to multiple antimicrobial agents and increased resistance gene expression following exposure to ceftriaxone using a protocol that simulated a patient treatmentin vitro. SevenSalmonella entericastrains survived a simulated patient treatmentin vitroand, following treatment, exhibited a significantly increased ceftriaxone MIC. Not only would these isolates be less responsive to further ceftriaxone treatment, but because theblaCMY-2genes are commonly located on large, multidrug-resistant plasmids, increased expression of theblaCMY-2gene may be associated with increased expression of other drug resistance genes located on the plasmid (N. D. Hanson and C. C. Sanders, Curr. Pharm. Des. 5:881–894, 1999). The results of this study demonstrate that a simulated patient treatment with ceftriaxone can alter the expression of antimicrobial resistance genes, includingblaCMY-2andfloRinS. entericaserovar Typhimurium andS. entericaserovar Newport. Additionally, we have shown increased MICs following a simulated patient treatment with ceftriaxone for tetracycline, amikacin, ceftriaxone, and cefepime, all of which have resistance genes commonly located on CMY-2 plasmids. The increases in resistance observed are significant and may have a negative impact on both public health and antimicrobial resistance ofSalmonella enterica.

scholarly journals Role of Antilipopolysaccharide Antibodies in Serum Bactericidal Activity against Salmonella enterica Serovar Typhimurium in Healthy Adults and Children in the United States

2013 ◽  
Vol 20 (10) ◽  
pp. 1491-1498 ◽  
Author(s):  
Estela Trebicka ◽  
Susan Jacob ◽  
Waheed Pirzai ◽  
Bryan P. Hurley ◽  
Bobby J. Cherayil
Keyword(s):  
United States ◽  
Bactericidal Activity ◽  
Salmonella Enterica ◽  
The United States ◽  
Healthy Children ◽  
Healthy Individuals ◽  
Serum Samples ◽  
Content Type ◽  
Serovar Typhimurium

ABSTRACTRecent observations from Africa have rekindled interest in the role of serum bactericidal antibodies in protecting against systemic infection withSalmonella entericaserovar Typhimurium. To determine whether the findings are applicable to other populations, we analyzed serum samples collected from healthy individuals in the United States. We found that all but 1 of the 49 adult samples tested had robust bactericidal activity againstS. Typhimurium in a standardin vitroassay. The activity was dependent on complement and could be reproduced by immunoglobulin G (IgG) purified from the sera. The bactericidal activity was inhibited by competition with soluble lipopolysaccharide (LPS) fromS. Typhimurium but not fromEscherichia coli, consistent with recognition of a determinant in the O-antigen polysaccharide. Sera from healthy children aged 10 to 48 months also had bactericidal activity, although it was significantly less than in the adults, correlating with lower levels of LPS-specific IgM and IgG. The lone sample in our collection that lacked bactericidal activity was able to inhibit killing ofS. Typhimurium by the other sera. The inhibition correlated with the presence of an LPS-specific IgM and was associated with decreased complement deposition on the bacterial surface. Our results indicate that healthy individuals can have circulating antibodies to LPS that either mediate or inhibit killing ofS. Typhimurium. The findings contrast with the observations from Africa, which linked bactericidal activity to antibodies against anS. Typhimurium outer membrane protein and correlated the presence of inhibitory anti-LPS antibodies with human immunodeficiency virus infection.

scholarly journals ARGONAUT II Study of the In Vitro Activity of Plazomicin against Carbapenemase-Producing Klebsiella pneumoniae

2020 ◽  
Vol 64 (5) ◽  
Author(s):  
Michael R. Jacobs ◽  
Caryn E. Good ◽  
Andrea M. Hujer ◽  
Ayman M. Abdelhamed ◽  
Daniel D. Rhoads ◽  
...  
Keyword(s):  
United States ◽  
16S Rrna ◽  
Klebsiella Pneumoniae ◽  
Great Lakes ◽  
The United States ◽  
Great Lakes Region ◽  
In Vitro Activity ◽  
Content Type ◽  
Carbapenem Resistant

ABSTRACT Plazomicin was tested against 697 recently acquired carbapenem-resistant Klebsiella pneumoniae isolates from the Great Lakes region of the United States. Plazomicin MIC50 and MIC90 values were 0.25 and 1 mg/liter, respectively; 680 isolates (97.6%) were susceptible (MICs of ≤2 mg/liter), 9 (1.3%) intermediate (MICs of 4 mg/liter), and 8 (1.1%) resistant (MICs of >32 mg/liter). Resistance was associated with rmtF-, rmtB-, or armA-encoded 16S rRNA methyltransferases in all except 1 isolate.

scholarly journals An Attenuated Salmonella enterica Serovar Typhimurium Strain and Galacto-Oligosaccharides Accelerate Clearance of Salmonella Infections in Poultry through Modifications to the Gut Microbiome

2017 ◽  
Vol 84 (5) ◽  
Author(s):  
M. Andrea Azcarate-Peril ◽  
Natasha Butz ◽  
Maria Belen Cadenas ◽  
Matthew Koci ◽  
Anne Ballou ◽  
...  
Keyword(s):  
United States ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Salmonella Enterica ◽  
The United States ◽  
Wild Type ◽  
Content Type ◽  
Salmonella Infections ◽  
Serovar Typhimurium ◽  
The Impact

ABSTRACT Salmonella is estimated to cause one million foodborne illnesses in the United States every year. Salmonella -contaminated poultry products are one of the major sources of salmonellosis. Given the critical role of the gut microbiota in Salmonella transmission, a manipulation of the chicken intestinal microenvironment could prevent animal colonization by the pathogen. In Salmonella , the global regulator gene fnr ( f umarate n itrate r eduction) regulates anaerobic metabolism and is essential for adapting to the gut environment. This study tested the hypothesis that an attenuated Fnr mutant of Salmonella enterica serovar Typhimurium (attST) or prebiotic galacto-oligosaccharides (GOS) could improve resistance to wild-type Salmonella via modifications to the structure of the chicken gut microbiome. Intestinal samples from a total of 273 animals were collected weekly for 9 weeks to evaluate the impact of attST or prebiotic supplementation on microbial species of the cecum, duodenum, jejunum, and ileum. We next analyzed changes to the gut microbiome induced by challenging the animals with a wild-type Salmonella serovar 4,[5],12:r:− (Nal r ) strain and determined the clearance rate of the virulent strain in the treated and control groups. Both GOS and the attenuated Salmonella strain modified the gut microbiome but elicited alterations of different taxonomic groups. The attST produced significant increases of Alistipes and undefined Lactobacillus , while GOS increased Christensenellaceae and Lactobacillus reuteri . The microbiome structural changes induced by both treatments resulted in a faster clearance after a Salmonella challenge. IMPORTANCE With an average annual incidence of 13.1 cases/100,000 individuals, salmonellosis has been deemed a nationally notifiable condition in the United States by the Centers for Disease Control and Prevention (CDC). Earlier studies demonstrated that Salmonella is transmitted by a subset of animals (supershedders). The supershedder phenotype can be induced by antibiotics, ascertaining an essential role for the gut microbiota in Salmonella transmission. Consequently, modulation of the gut microbiota and modification of the intestinal microenvironment could assist in preventing animal colonization by the pathogen. Our study demonstrated that a manipulation of the chicken gut microbiota by the administration of an attenuated Salmonella strain or prebiotic galacto-oligosaccharides (GOS) can promote resistance to Salmonella colonization via increases of beneficial microorganisms that translate into a less hospitable gut microenvironment.

scholarly journals Activity of Ceftaroline and Epidemiologic Trends in Staphylococcus aureus Isolates Collected from 43 Medical Centers in the United States in 2009

2011 ◽  
Vol 55 (9) ◽  
pp. 4154-4160 ◽  
Author(s):  
Sandra S. Richter ◽  
Kristopher P. Heilmann ◽  
Cassie L. Dohrn ◽  
Fathollah Riahi ◽  
Andrew J. Costello ◽  
...  
Keyword(s):  
United States ◽  
Staphylococcus Aureus ◽  
The United States ◽  
Surveillance Program ◽  
Content Type ◽  
Type Iv ◽  
Medical Centers ◽  
High Level ◽  
Resistance Rates

ABSTRACTAStaphylococcus aureussurveillance program was initiated in the United States to examine thein vitroactivity of ceftaroline and epidemiologic trends. Susceptibility testing by Clinical and Laboratory Standards Institute broth microdilution was performed on 4,210 clinically significant isolates collected in 2009 from 43 medical centers. All isolates were screened formecAby PCR and evaluated by pulsed-field gel electrophoresis. Methicillin-resistantS. aureus(MRSA) were analyzed for Panton-Valentine leukocidin (PVL) genes and the staphylococcal cassette chromosomemec(SCCmec) type. All isolates had ceftaroline MICs of ≤2 μg/ml with an MIC50of 0.5 and an MIC90of 1 μg/ml. The overall resistance rates, expressed as the percentages of isolates that were intermediate and resistant (or nonsusceptible), were as follows: ceftaroline, 1.0%; clindamycin, 30.2% (17.4% MIC ≥ 4 μg/ml; 12.8% inducible); daptomycin, 0.2%; erythromycin, 65.5%; levofloxacin, 39.9%; linezolid, 0.02%; oxacillin, 53.4%; tetracycline, 4.4%; tigecycline, 0%; trimethoprim-sulfamethoxazole, 1.6%; vancomycin, 0%; and high-level mupirocin, 2.2%. ThemecAPCR was positive for 53.4% of the isolates. The ceftaroline MIC90s were 0.25 μg/ml for methicillin-susceptibleS. aureusand 1 μg/ml for MRSA. Among the 2,247 MRSA isolates, 51% were USA300 (96.9% PVL positive, 99.7% SCCmectype IV) and 17% were USA100 (93.4% SCCmectype II). The resistance rates for the 1,137 USA300 MRSA isolates were as follows: erythromycin, 90.9%; levofloxacin, 49.1%; clindamycin, 7.6% (6.2% MIC ≥ 4 μg/ml; 1.4% inducible); tetracycline, 3.3%; trimethoprim-sulfamethoxazole, 0.8%; high-level mupirocin, 2.7%; daptomycin, 0.4%; and ceftaroline and linezolid, 0%. USA300 is the dominant clone causing MRSA infections in the United States. Ceftaroline demonstrated potentin vitroactivity against recentS. aureusclinical isolates, including MRSA, daptomycin-nonsusceptible, and linezolid-resistant strains.

scholarly journals Antimicrobial Resistance in Salmonella in the United States from 1948 to 1995

2016 ◽  
Vol 60 (4) ◽  
pp. 2567-2571 ◽  
Author(s):  
Daniel A. Tadesse ◽  
Aparna Singh ◽  
Shaohua Zhao ◽  
Mary Bartholomew ◽  
Niketta Womack ◽  
...  
Keyword(s):  
United States ◽  
Retrospective Study ◽  
Multidrug Resistance ◽  
Antimicrobial Resistance ◽  
Salmonella Enterica ◽  
Antimicrobial Agents ◽  
The United States ◽  
Content Type ◽  
The Past ◽  
The 1950S

ABSTRACTWe conducted a retrospective study of 2,149 clinicalSalmonellastrains to help document the historical emergence of antimicrobial resistance. There were significant increases in resistance to older drugs, including ampicillin, chloramphenicol, streptomycin, sulfamethoxazole, and tetracycline, which were most common inSalmonella entericaserotype Typhimurium. An increase in multidrug resistance was observed for each decade since the 1950s. These data help show howSalmonellaevolved over the past 6 decades, after the introduction of new antimicrobial agents.

scholarly journals Interaction of Antibiotics with Innate Host Defense Factors against Salmonella enterica Serotype Newport

mSphere ◽  
2017 ◽  
Vol 2 (6) ◽  
Author(s):  
George Sakoulas ◽  
Monika Kumaraswamy ◽  
Armin Kousha ◽  
Victor Nizet
Keyword(s):  
Innate Immunity ◽  
Immune System ◽  
Innate Immune System ◽  
Salmonella Enterica ◽  
Clinical Performance ◽  
Innate Immune ◽  
Content Type ◽  
Antimicrobial Assay

ABSTRACT It is becoming increasingly understood that the current paradigms of in vitro antimicrobial susceptibility testing may have significant shortcomings in predicting activity in vivo. This study evaluated the activity of several antibiotics alone and in combination against clinical isolates of Salmonella enterica serotype Newport (meningitis case) utilizing both conventional and physiological media. In addition, the interactions of these antibiotics with components of the innate immune system were evaluated. Azithromycin, which has performed quite well clinically despite high MICs in conventional media, was shown to be more active in physiological media and to enhance innate immune system killing. Alternatively, chloramphenicol did not show enhanced immune system killing, paralleling its inferior clinical performance to other antibiotics that have been used to treat Salmonella meningitis. These findings are important additions to the building understanding of current in vitro antimicrobial assay limitations that hopefully will amount to future improvements in these assays to better predict clinical efficacy and activity in vivo. This study examines the pharmacodynamics of antimicrobials that are used to treat Salmonella with each other and with key components of the innate immune system. Antimicrobial synergy was assessed using time-kill and checkerboard assays. Antimicrobial interactions with innate immunity were studied by employing cathelicidin LL-37, whole-blood, and neutrophil killing assays. Ceftriaxone and ciprofloxacin were found to be synergistic in vitro against Salmonella enterica serotype Newport. Ceftriaxone, ciprofloxacin, and azithromycin each demonstrated synergy with the human cathelicidin defense peptide LL-37 in killing Salmonella. Exposure of Salmonella to sub-MICs of ceftriaxone resulted in enhanced susceptibility to LL-37, whole blood, and neutrophil killing. The activity of antibiotics in vivo against Salmonella may be underestimated in bacteriologic media lacking components of innate immunity. The pharmacodynamic interactions of antibiotics used to treat Salmonella with each other and with components of innate immunity warrant further study in light of recent findings showing in vivo selection of antimicrobial resistance by single agents in this pathogen. IMPORTANCE It is becoming increasingly understood that the current paradigms of in vitro antimicrobial susceptibility testing may have significant shortcomings in predicting activity in vivo. This study evaluated the activity of several antibiotics alone and in combination against clinical isolates of Salmonella enterica serotype Newport (meningitis case) utilizing both conventional and physiological media. In addition, the interactions of these antibiotics with components of the innate immune system were evaluated. Azithromycin, which has performed quite well clinically despite high MICs in conventional media, was shown to be more active in physiological media and to enhance innate immune system killing. Alternatively, chloramphenicol did not show enhanced immune system killing, paralleling its inferior clinical performance to other antibiotics that have been used to treat Salmonella meningitis. These findings are important additions to the building understanding of current in vitro antimicrobial assay limitations that hopefully will amount to future improvements in these assays to better predict clinical efficacy and activity in vivo.

Sign in / Sign up

Export Citation Format

Share Document