Prevalence Of Antibiotic-resistant Pathogens Research Articles

The evolution of antimicrobial peptide resistance in Pseudomonas aeruginosa is severely constrained by random peptide mixtures.

The prevalence of antibiotic-resistant pathogens has become a major threat to public health, requiring swift initiatives for discovering new strategies to control bacterial infections. Hence, antibiotic stewardship and rapid diagnostics, but also the development, and prudent use, of novel effective antimicrobial agents are paramount. Ideally, these agents should be less likely to select for resistance in pathogens than currently available conventional antimicrobials. The usage of antimicrobial peptides (AMPs), key components of the innate immune response, and combination therapies, have been proposed as strategies to diminish the emergence of resistance. Herein, we investigated whether newly developed random antimicrobial peptide mixtures (RPMs) can significantly reduce the risk of resistance evolution in vitro to that of single sequence AMPs, using the ESKAPE pathogen Pseudomonas aeruginosa (P. aeruginosa) as a model gram-negative bacterium. Infections of this pathogen are difficult to treat due the inherent resistance to many drug classes, enhanced by the capacity to form biofilms. P. aeruginosa was experimentally evolved in the presence of AMPs or RPMs, subsequentially assessing the extent of resistance evolution and cross-resistance/collateral sensitivity between treatments. Furthermore, the fitness costs of resistance on bacterial growth were studied and whole-genome sequencing used to investigate which mutations could be candidates for causing resistant phenotypes. Lastly, changes in the pharmacodynamics of the evolved bacterial strains were examined. Our findings suggest that using RPMs bears a much lower risk of resistance evolution compared to AMPs and mostly prevents cross-resistance development to other treatments, while maintaining (or even improving) drug sensitivity. This strengthens the case for using random cocktails of AMPs in favour of single AMPs, against which resistance evolved in vitro, providing an alternative to classic antibiotics worth pursuing.

Antimicrobial resistance in patients with COVID-19: a systematic review and meta-analysis

Frequent use of antibiotics in patients with COVID-19 threatens to exacerbate antimicrobial resistance. We aimed to establish the prevalence and predictors of bacterial infections and antimicrobial resistance in patients with COVID-19. We did a systematic review and meta-analysis of studies of bacterial co-infections (identified within ≤48 h of presentation) and secondary infections (>48 h after presentation) in outpatients or hospitalised patients with COVID-19. We searched the WHO COVID-19 Research Database to identify cohort studies, case series, case-control trials, and randomised controlled trials with populations of at least 50 patients published in any language between Jan 1, 2019, and Dec 1, 2021. Reviews, editorials, letters, pre-prints, and conference proceedings were excluded, as were studies in which bacterial infection was not microbiologically confirmed (or confirmed via nasopharyngeal swab only). We screened titles and abstracts of papers identified by our search, and then assessed the full text of potentially relevant articles. We reported the pooled prevalence of bacterial infections and antimicrobial resistance by doing a random-effects meta-analysis and meta-regression. Our primary outcomes were the prevalence of bacterial co-infection and secondary infection, and the prevalence of antibiotic-resistant pathogens among patients with laboratory-confirmed COVID-19 and bacterial infections. The study protocol was registered with PROSPERO (CRD42021297344). We included 148 studies of 362 976 patients, which were done between December, 2019, and May, 2021. The prevalence of bacterial co-infection was 5·3% (95% CI 3·8-7·4), whereas the prevalence of secondary bacterial infection was 18·4% (14·0-23·7). 42 (28%) studies included comprehensive data for the prevalence of antimicrobial resistance among bacterial infections. Among people with bacterial infections, the proportion of infections that were resistant to antimicrobials was 60·8% (95% CI 38·6-79·3), and the proportion of isolates that were resistant was 37·5% (26·9-49·5). Heterogeneity in the reported prevalence of antimicrobial resistance in organisms was substantial (I2=95%). Although infrequently assessed, antimicrobial resistance is highly prevalent in patients with COVID-19 and bacterial infections. Future research and surveillance assessing the effect of COVID-19 on antimicrobial resistance at the patient and population level are urgently needed. WHO.

Bacterial Isolates and Antibacterial Resistance Patterns in a Patient with Acute Exacerbation of Chronic Obstructive Pulmonary Disease in a Tertiary Teaching Hospital, Southwest Ethiopia.

Introduction Chronic obstructive pulmonary disease (COPD) is a major cause of chronic morbidity and mortality worldwide. The natural course of COPD is characterized by acute exacerbation. Infectious agents, particularly bacteria, cause exacerbation of COPD in the majority. This study aimed to determine the bacteriology and antibiotic resistance patterns among patients with acute exacerbations of COPD (AECOPD) at Jimma Medical Center. Methods A cross-sectional study was conducted from March to October 2019. Demographic, clinical, and sputa samples were collected from 39 study participants, who were diagnosed with AECOPD. Bacterial pathogens were identified using standard bacteriological techniques, and anti-microbial susceptibility testing was done by Kirby Bauer's disk diffusion method. Extended-spectrum β-lactamase (ESβL) and carbapenemase production were confirmed by MASTTM D68C and MASTTM D73C combination disc sets, respectively. Chi-square and odds ratios were calculated. Results Overall, 69.2% (27/39) of sputum samples were confirmed to be culture-positive. A total of 32 bacterial isolates with 78.1% (25/32) Gram-negative and 21.9% (7/32) Gram-positive bacteria were identified. The predominant bacterial isolates were Pseudomonas aeruginosa 21.9% (7/32), Klebsiella pneumoniae 18.75% (6/32), and Staphylococcus aureus 15.62% (7/32). Overall, 30 (93.8%) of the isolates were multidrug-resistant (MDR). About 48% (12/25) and 8 (32%)of gram negative bacterial isolates were ESBL betalatemase and OXA-48 carbapenemase producers, respectively. Having two or more exacerbation experiences in the previous year were found to be important determinants of the sputum culture positivity. Conclusions High rates of MDR, ESBL, and carbapenemase producer bacteria were isolated from patients with AECOPD. Empiric antibiotic therapy should consider the prevalence of antibiotic-resistant pathogens and the factor that may increase the occurrence of MDR bacterial pathogens.

The Many Applications of Engineered Bacteriophages-An Overview.

Since their independent discovery by Frederick Twort in 1915 and Felix d’Herelle in 1917, bacteriophages have captured the attention of scientists for more than a century. They are the most abundant organisms on the planet, often outnumbering their bacterial hosts by tenfold in a given environment, and they constitute a vast reservoir of unexplored genetic information. The increased prevalence of antibiotic resistant pathogens has renewed interest in the use of naturally obtained phages to combat bacterial infections, aka phage therapy. The development of tools to modify phages, genetically or chemically, combined with their structural flexibility, cargo capacity, ease of propagation, and overall safety in humans has opened the door to a myriad of applications. This review article will introduce readers to many of the varied and ingenious ways in which researchers are modifying phages to move them well beyond their innate ability to target and kill bacteria.

Synergistic interactions of ionic liquids and antimicrobials improve drug efficacy.

SummaryCombinations of ionic liquids (ILs) with antimicrobial compounds have been shown to produce synergistic activities in model liposomes. In this study, imidazolium chloride-based ILs with alkyl tail length variations are combined with commercially available, small-molecule antimicrobials to examine the potential for combinatorial and synergistic antimicrobial effects on P. aeruginosa, E. coli, S. aureus, and S. cerevisiae. The effects of these treatments in a human cell culture model indicate the cytotoxic limits of ILs paired with antimicrobials. The analysis of these ILs demonstrates that the length of the alkyl chain on the IL molecule is proportional to both antimicrobial activity and cytotoxicity. Moreover, the ILs which exhibit synergy with small-molecule antibiotics appear to be acting in a membrane permeabilizing manner. Collectively, results from these experiments demonstrate an increase in antimicrobial efficacy with specific IL + antimicrobial combinations on microbial cultures while maintaining low cytotoxicity in a mammalian cell culture model.

Mathematical basis for the assessment of antibiotic resistance and administrative counter-strategies.

Diversity as well as temporal and spatial changes of the proportional abundances of different antibiotics (cycling, mixing or combinations thereof) have been hypothesised to be an effective administrative control strategy in hospitals to reduce the prevalence of antibiotic-resistant pathogens in nosocomial or community-acquired infections. However, a rigorous assessment of the efficacy of these control strategies is lacking. The main purpose here is to present a mathematical framework for the assessment of control stategies from a processual stance. To this end, we adopt diverse measures of heterogeneity and diversity of proportional abundances based on the concept of entropy from other fields and adapt them to the needs in assessing the impact of variations in antibiotic consumption on antibiotic resistance. Thereby, we derive a family of diversity measures whose members exhibit different degrees of complexity. Most important, we extent these measures such that they account for the assessment of temporal changes in heterogeneity including otherwise undetected diversity-invariant permutations of antibiotics consumption and prevalence of resistant pathogens. We apply a correlation analysis for the assessment of associations between changes of heterogeneities on the antibiotics and on the pathogen side. As a showcase, which serves as a proof-of-principle, we apply the derived methods to records of antibiotic consumption and prevalence of antibiotic-resistant germs from University Hospital Dresden (cf. supplement "DiebnerEtAl_Data-Supplement"). Besides the quantification of heterogeneities of antibiotics consumption and antibiotic resistance, we show that a reduction of prevalence of antibiotic-resistant germs correlates with a temporal change of similarity with respect to the first observation of antibiotics consumption, although heterogeneity remains approximately constant. Although an interventional study is pending, our mathematical framework turns out to be a viable concept for the assessment and optimisation of control strategies intended to reduce antibiotic resistance.

A retrospective cross-sectional study of urinary tract infections and prevalence of antibiotic resistant pathogens in patients with diabetes mellitus from a public hospital in Surabaya, Indonesia

Diabetes mellitus (DM) is a metabolic disease that can cause many complications. The occurrence of urinary tract infection is also considered to be the cause of complications in patients with DM. This study aimed to evaluate the prevalence of urinary tract infection (UTI) and antibiotic-resistant bacteria found in urine culture from patients with DM in Surabaya, Indonesia. This study was conducted with a retrospective cross-sectional study design, using a database of 1551 patients with DM admitted to Haji Hospital, Surabaya, Indonesia, from January 2017 to December 2018. Data regarding the bacteria isolated from urine and antimicrobial sensitivity were analyzed. The prevalence of UTI was 3.93% - 61 patients were confirmed with urine culture for UTI diagnosis. The predominant isolates found were Escherichia coli (24.5%) and Enterococcus faecalis (8%). This study also showed multidrug-resistant organisms (MDRO) found in UTI such as Escherichia coli MDRO (3.3 %), Klebsiella pneumoniae MDRO (3.3%), Acinetobacter baumannii MDRO (1.6%), extended-spectrum beta-lactamase (ESBL) Escherichia coli (3.3%). The E. coli were sensitive to fosfomycin (93%), meropenem (93%) and nitrofurantoin (67%). No significant difference in the prevalence of UTI was found among ages, sex, and duration of disease in all patients with DM. The cases of UTI seen in patients with DM show the importance of monitoring UTI occurrence in this patient category to ensure better treatment for these patients.

Increasing burden of biliary tract infection caused by extended-spectrum beta-lactamase-producing organisms in Korea: A nationwide population-based study.

Biliary tract infections (BTIs) are a major cause of bacteremia. The prevalence of antibiotic-resistant pathogens in BTI patients is reported to be increasing. We used a nationwide database to evaluate the prevalence of, and risk factors for, BTIs caused by extended-spectrum beta-lactamase-producing organisms (ESBL-PO) in Korea. Patients with a BTI diagnosis, an admission history, a history of a BTI-related procedure, and antibiotic use for ≥4days between 2007 and 2016 were identified from the Health Insurance Review and Assessment Service database. A BTI treated with carbapenems (BTI-TC) was used as the surrogate for a BTI caused by ESBL-PO. We conducted a multivariate logistic regression analysis to determine the risk factors for BTI-TC. In total, 341002 patients were enrolled. The overall percentage of BTI-TC among BTIs was 2.4%, with an increasing annual trend (P<0.0001). The risk of acute cholangitis caused by ESBL-PO increased significantly in men, older patients, patients with comorbidities, patients with a history of a biliary procedure within the previous year, and patients with a history of antibiotic use within the previous 90days. Regarding antibiotic use, the patients at highest risk were those previously prescribed carbapenems (adjusted odds ratio, 4.77; P<0.0001). The prevalence of BTIs caused by ESBL-PO has increased during the last 10years. Initial carbapenem therapy should be considered for elderly patients with acute cholangitis if they have had a previous biliary procedure and/or a history of carbapenem administration within the previous 90days.

A Critical Review and Perspective of Honey in Tissue Engineering and Clinical Wound Healing.

Significance: Historically, honey has been regarded as a potent agent in bacterial inhibition and wound healing. An increased prevalence of antibiotic resistant pathogens spurred an initial resurgence in honey's clinical popularity, with it quickly finding a place in wound care and regenerative medicine. However, this renewed usage demanded a need for improved delivery and overall research of its bioactive properties. This review provides an overview of the antibacterial properties and clinical use of honey. Recent Advances: The past and present clinical use of honey is noted, focusing specifically on burns and ulcers, as these are the most common applications of the natural agent. While honey is often used without modification clinically, there are also commercially available products ranging from dressings to gels, which are discussed. Critical Issues: Despite these products growing in popularity, the need for improved delivery and a structure to support wound healing could improve the treatment method. Future Directions: Tissue engineering scaffolds can provide an alternative method of honey delivery with research focusing primarily on electrospun scaffolds, hydrogels, and cryogels. Current studies on these scaffolds are discussed with respect to their advantages and potential for future clinical work. Overall, this review provides a comprehensive overview of the properties of honey, its current use in wound healing, and the potential for future incorporation into tissue-engineered scaffolds to provide an innovative wound healing agent.

Inducible lung epithelial resistance requires multisource reactive oxygen species generation to protect against bacterial infections.

Pneumonia remains a global health threat, in part due to expanding categories of susceptible individuals and increasing prevalence of antibiotic resistant pathogens. However, therapeutic stimulation of the lungs’ mucosal defenses by inhaled exposure to a synergistic combination of Toll-like receptor (TLR) agonists known as Pam2-ODN promotes mouse survival of pneumonia caused by a wide array of pathogens. This inducible resistance to pneumonia relies on intact lung epithelial TLR signaling, and inducible protection against viral pathogens has recently been shown to require increased production of epithelial reactive oxygen species (ROS) from multiple epithelial ROS generators. To determine whether similar mechanisms contribute to inducible antibacterial responses, the current work investigates the role of ROS in therapeutically-stimulated protection against Pseudomonas aerugnosa challenges. Inhaled Pam2-ODN treatment one day before infection prevented hemorrhagic lung cytotoxicity and mouse death in a manner that correlated with reduction in bacterial burden. The bacterial killing effect of Pam2-ODN was recapitulated in isolated mouse and human lung epithelial cells, and the protection correlated with inducible epithelial generation of ROS. Scavenging or targeted blockade of ROS production from either dual oxidase or mitochondrial sources resulted in near complete loss of Pam2-ODN-induced bacterial killing, whereas deficiency of induced antimicrobial peptides had little effect. These findings support a central role for multisource epithelial ROS in inducible resistance against a bacterial pathogen and provide mechanistic insights into means to protect vulnerable patients against lethal infections.

Elucidating the survival and response of carbapenem resistant Klebsiella pneumoniae after exposure to imipenem at sub-lethal concentrations

ABSTRACTThe increasing prevalence of antibiotic resistant pathogens poses a serious threat to global health. However, less emphasis has been placed to co-relate the gene expression and metabolism of antibiotic resistant pathogens. This study aims to elucidate gene expression and variations in metabolism of multidrug resistant Klebsiella pneumoniae after exposure to antibiotics. Phenotypic responses of three genotypically distinct carbapenem resistant Klebsiella pneumoniae (CRKP) strains untreated and treated with sub-lethal concentrations of imipenem were investigated via phenotype microarrays (PM). The gene expression and metabolism of the strain harboring blaNDM-1 before and after exposure to sub-lethal concentration of imipenem were further investigated by RNA-sequencing (RNA-Seq) and 1H NMR spectroscopy respectively. Most genes related to cell division, central carbon metabolism and nucleotide metabolism were downregulated after imipenem treatment. Similarly, 1H NMR spectra obtained from treated CRKP showed decrease in levels of bacterial end products (acetate, pyruvate, succinate, formate) and metabolites involved in nucleotide metabolism (uracil, xanthine, hypoxanthine) but elevated levels of glycerophosphocholine. The presence of anserine was also observed for the treated CRKP while FAPγ-adenine and methyladenine were only present in untreated bacterial cells. As a conclusion, the studied CRKP strain exhibited decrease in central carbon metabolism, cell division and nucleotide metabolism after exposure to sub-lethal concentrations of imipenem. The understanding of the complex biological system of this multidrug resistant bacterium may help in the development of novel strategies and potential targets for the management of the infections.

Efficiency of a bacteriophage in controlling vibrio infection in the juvenile sea cucumber Apostichopus japonicus

Vibro cyclitrophicus is thought to be responsible for the cause of severe infection in juvenile sea cucumber (Apostichopus japonicus). Increases in the prevalence of antibiotic resistant pathogens have promoted us to develop effective agents to antibiotics for combating microbial infection among animals as well as human. In the present study, we isolated a bacteriophage with the ability to cleave V. cyclitrophicus present in the sewage of sea cucumber farms. This bacteriophage was designated as phage vB_VcyS_Vc1 (Vibrio phage Vc1). A one-step growth curve analysis of the phage revealed eclipse and latent periods of 25 and 45min, respectively, with a burst size of 215PFU/infected cell. Morphological analysis revealed the phage belongs to family of Siphoviridae. Furthermore, genomic sequencing results revealed a double-stranded DNA containing 44,541bp with a G+C content of 44.16%. Forty four coding sequences were annotated in the genome, and nineteen of these were associated with a known function. Genes related to virulence and toxins were not detected in the genome. In addition, a prevention experiment conducted in a marine environment demonstrated that the phage increased the survival rate of juvenile sea cucumbers (18±2g) from 18% to 81% when the sea cucumber were fed with feedstuff containing the freeze-dried phage powder, 58% when the sea cucumber was injected with purified phages (MOI=10), and 63% when the sea cucumbers were immersed in a suspension containing purified phages. Notably, when the phage provided nearly the same protection to the sea cucumbers as antibiotic when it was fed to the sea cucumbers in the form of freeze-dried powder mixed with feedstuff. Taken together, the results demonstrated that the use of phage to control the infection of V. cyclitrophicus in sea cucumber may be a feasible alternative to antibiotics. Statement of relevanceThe A. japonicus (sea cucumber) is the most profitable aquaculture animal with the highest output as single variety in China, which is of high nutritional value and economic value. In the past decade, as the growth of the market demand, A. japonicus's artificial breeding scale expands rapidly and the sea cucumber industry has become a vigorous sector in China aquaculture. However, with the high density and intensive development model of A. japonicus breeding, the various diseases have resulted in serious economic losses. Skin ulceration syndrome (SUS) is one of the most epidemic and serious diseases that affect sea cucumbers. At present, sanitizer and antibiotics are still commonly used in farms or hatcheries to control the bacterial disease in juvenile sea cucumbers, which resulted in the environment pollution and antibiotic residues. Nowadays, increased appearance of antibiotic resistant phenomenon promoted us to develop effective agents. Hence, alternative strategies to antibiotics should be further developed. This study was the first to monitor the effectiveness of using feedstuff mixed with freeze-dried phage powder as a form of protection for sea cucumber against vibrio infection, and demonstrated the effectiveness of phage in the control of pathogen in aquaculture.

Neonatal nosocomial bloodstream infections at a referral hospital in a middle-income country: burden, pathogens, antimicrobial resistance and mortality

Background:Data on nosocomial bloodstream infection (BSI) rates, pathogens, mortality and antimicrobial resistance in African neonates are limited.Methods:Nosocomial neonatal BSI at Tygerberg Hospital, Cape Town were retrospectively reviewed between 1 January 2009 and 31 December 2013. Laboratory and hospital data were used to determine BSI rates, pathogen profile, mortality and antimicrobial resistance in selected nosocomial pathogens.Results:Of 6521 blood cultures taken over 5 years, 1145 (17.6%) were culture-positive, and 717 (62.6%) discrete nosocomial BSI episodes were identified. Nosocomial BSI rates remained unchanged over time (overall 3.9/1000 patient days, 95% CI 3.6–4.2, χ2 for trend P = 0.23). Contamination rates were relatively high (5.1%, 95% CI 4.6–5.7%). Among BSI pathogens, Gram-negatives predominated (65% vs 31% Gram-positives and 4% fungal); Klebsiella pneumoniae (235, 30%), Staphylococcus aureus (112, 14%) and Enterococci (88, 11%) were most prevalent. Overall crude BSI mortality was 16% (112/717); Gram-negative BSI was significantly associated with mortality (P = 0.007). Mortality occurred mostly in neonates of very low (33/112, 29%) or extremely low (53/112, 47%) birthweight. Deaths attributed to nosocomial BSI declined significantly over time (χ2 for trend P = 0.01). The prevalence of antibiotic-resistant pathogens was high: methicillin-resistant Staphylococcus aureus 66%, multidrug-resistant A. baumanni 90% and extended-spectrum β-lactamase-producing K. pneumoniae 73%.Conclusion:The burden of nosocomial neonatal BSI at this middle-income country referral neonatal unit is substantial and remained unchanged over the study period, although attributable mortality declined significantly. Nosocomial BSI pathogens exhibited high levels of antimicrobial resistance.

Quantitative Impact of Neutrophils on Bacterial Clearance in a Murine Pneumonia Model

The rapid increase in the prevalence of antibiotic-resistant pathogens is a global problem that has challenged our ability to treat serious infections. Currently, clinical decisions on treatment are often based on in vitro susceptibility data. The role of the immune system in combating bacterial infections is unequivocal, but it is not well captured quantitatively. In this study, the impact of neutrophils on bacterial clearance was quantitatively assessed in a murine pneumonia model. In vitro time-growth studies were performed to determine the growth rate constants of Acinetobacter baumannii ATCC BAA 747 and Pseudomonas aeruginosa PAO1. The absolute neutrophil count in mice resulting from different cyclophosphamide preparatory regimens was determined. The dynamic change of bacterial (A. baumannii BAA 747) burden in mice with graded immunosuppression over 24 h was captured by a mathematical model. The fit to the data was satisfactory (r(2) = 0.945). The best-fit maximal kill rate (K(k)) of the bacterial population by neutrophils was 1.743 h(-1), the number of neutrophils necessary for 50% maximal killing was 190.8/μl, and the maximal population size was 1.8 × 10(9) CFU/g, respectively. Using these model parameter estimates, the model predictions were subsequently validated by the bacterial burden change of P. aeruginosa PAO1 at 24 h. A simple mathematical model was proposed to quantify the contribution of neutrophils to bacterial clearance and predict the bacterial growth/suppression in animals. Our results provide a novel framework to link in vitro and in vivo information and may be used to improve clinical treatment of bacterial infections.

Characterization of a potent antimicrobial lipopeptide via coarse-grained molecular dynamics

The prevalence of antibiotic-resistant pathogens is a major medical concern, prompting increased interest in the development of novel antimicrobial compounds. One such set of naturally occurring compounds, known as antimicrobial peptides (AMPs), have broad-spectrum activity, but come with many limitations for clinical use. Recent work has resulted in a set of antimicrobial lipopeptides (AMLPs) with micromolar minimum inhibitory concentrations and excellent selectivity for bacterial membranes. To characterize a potent, synthetic lipopeptide, C16-KGG K, we used multi-microsecond coarse-grained simulations with the MARTINI forcefield, with a total simulation time of nearly 46 μs. These simulations show rapid binding of C16-KGG K, which forms micelles in solution, to model bacterial lipid bilayers. Furthermore, upon binding to the surface of the bilayer, these lipopeptides alter the local lipid organization by recruiting negatively charged POPG lipids to the site of binding. It is likely that this drastic reorganization of the bilayer has major effects on bilayer dynamics and cellular processes that depend on specific bilayer compositions. By contrast, the simulations revealed no association between the lipopeptides and model mammalian bilayers. These simulations provide biophysical insights into lipopeptide selectivity and suggest a possible mechanism for antimicrobial action. This article is part of a Special Issue entitled: Membrane protein structure and function.

Characterization of Potent Antimicrobial Lipopeptide via All-Atom and Coarse-Grained Molecular Dynamics

The prevalence of antibiotic resistant pathogens is a major medical concern, prompting increased interest in the development of novel antimicrobial compounds. To characterize a potent, synthetic lipopeptide, C16-KGGK, microsecond time-scale all-atom simulations with the CHARMM forcefield are utilized. This lipopeptide targets the bacterial membrane, but the binding and reorganization processes are extremely slow. To increase simulation speed, supplemental coarse-grained simulations with the MARTINI forcefield are used. This combination provides insights into the structure, dynamics, binding and mechanism of antimicrobial action.

Use of Pneumococcal Conjugate Vaccine to Decrease Rates of Bacterial Meningitis

Bacterial meningitis is a common cause of serious illness and death in both developed and developing countries. Case-fatality rates are high, ranging from 10% to 50% among all ages [1, 2], and the rate of lifelong sequelae exceeds 30% even in countries with a high level of hospital care [3, 4] . The increasing prevalence of antibioticresistant pathogens complicates the treatment of meningitis [5]. In the United States, as in other countries that have adopted the use of Haemophilus influenzae b vaccine, Streptococcus pneumoniae is the leading cause of bacterial meningitis, followed by Neisseria meningitidis [2, 6]. The risk of developing pneumococcal meningitis is highest in the extremes of age and in individuals with chronic diseases, including those who are immunocompromised. After the introduction of a 7-valent

Antimicrobial resistance in major pathogens of hospital-acquired pneumonia in Asian countries

Antimicrobial resistance is a worldwide problem. For patients with hospital-acquired or ventilator-associated pneumonia, resistant pathogens pose a significant challenge to successful treatment outcomes and to the cost-effective delivery of health care. In the developing world, antibiotic resistance may be relatively more prevalent compared with Western countries. Common resistant pathogens include methicillin-resistant Staphylococcus aureus, multidrug resistant Pseudomonas aeruginosa, multidrug resistant Acinetobacter species, and extended-spectrum beta-lactamase-producing strains of Escherichia coli and Klebsiella pneumoniae. The emergence of these strains has provided a major impetus toward development of the present consensus treatment recommendations of the Asian HAP Working Group. The following review provides summary data regarding the incidence and prevalence of antibiotic-resistant pathogens in 10 Asian countries.

Excessive Use of Antibiotics: Are We Losing the Battle?

Many studies and editorials have emphasized the increasing prevalence of antibiotic-resistant pathogens and the relation of antibiotic overuse to this