Multidrug-resistant Microbes Research Articles

The Medical Educators' Contribution to Curtailing Antimicrobial Resistance

The European Commission has stated that antimicrobial resistance now takes the lives of approximately 25 000 patients each year throughout the European Union.1 While investing in research will ultimately lead to the discovery of new antimicrobial agents, basic educational groundwork is likely to be just as important. Prescribing antibiotics inappropriately is the major cause of antibiotic resistance.2 Two years ago, in a 1000-bed North East General Hospital, I audited, with Hospital approval, the application of diagnostic criteria for community-acquired pneumonia (CAP) and acute exacerbation of chronic obstructive pulmonary disease and subsequent compliance with Hospital antimicrobial policy. While 92% of diagnoses complied with Hospital guidelines, inappropriate antimicrobial prescribing totalled 50%. The main sources of this deficit were two-fold: poor application of scores from CURB-65 (a simple system that assigns up to 5 points for clinical features of pneumonia: Confusion, Urea [serum] level, Respiratory rate, Blood pressure, Age over 65)3 in differentiating among mild, moderate, and severe cases of CAP, and reliance on anecdotal “evidence” and therefore ignoring Hospital antimicrobial policy. Simple measures such as the availability of a CURB-65 assessment tool and focused education that targets antimicrobial reasoning could help reduce this deficit and thus reduce the emergence of antimicrobial resistance. While it is impossible to use this reasoning to explain antimicrobial resistance alone, it serves as an indicator that fundamentally, we should do better with what we have while seeking new antimicrobials. An audit demonstrated that educating junior doctors (residents) and using a restricted group of antibiotics resulted in a reduced incidence of multidrug-resistant microbes.4 In its recent document “Tomorrows Doctors,” the United Kingdom's General Medical Council defined standards and outcomes of undergraduate teaching.5 Although general principles are addressed, complexities and practicalities of antimicrobial prescribing are not. As a newly qualified junior doctor, I feel my undergraduate training prepared me well with regard to the knowledge and skills I now use. However, I feel more time could have been devoted to discussing the basics of practicing, particularly the intricacies of prescribing common drugs such as antibiotics. The European Commission has assigned approximately €600 million ($735 million US) to research tackling antibiotic resistance.1 If a small fraction of this amount were now invested in educating junior doctors about antimicrobial prescribing, we would have already laid the foundations for safeguarding the future of newly discovered antimicrobials against pathogen resistance, thus beginning to reverse the escalating problem of antimicrobial resistance.

Cationic amphiphilic alpha-helical peptides for the treatment of carbapenem-resistant Acinetobacter baumannii infection

The emergence of multidrug-resistant Gram-negative bacteria, in particular Acinetobacter baumannii and Pseudomonas aeruginosa, is a critical clinical problem worldwide. Antimicrobial peptides (AMPs) have received increasing attention due to their ability to overcome multidrug-resistant microbes. We recently reported that cysteine-functionalized alpha-helical peptides LLKKLLKKC and CLLKKLLKKC effectively eradicated Gram-negative bacteria in vitro. In this study, the antibacterial properties of these peptides against carbapenem-resistant clinical isolates of A. baumannii were studied both in vitro and in vivo. The minimum inhibitory concentrations (MICs) of the peptides against 20 clinical isolates of carbapenem-resistant A. baumannii were determined in comparison with imipenem. The results showed that the A. baumannii isolates were more susceptible to (LLKK)2C than to C(LLKK)2C in vitro, and 90% of the 20 tested strains had an MIC of lower than or equal to 36.8 and 63.1 μmol/L, respectively. However, the bactericidal effect of C(LLKK)2C was much faster than that of (LLKK)2C. Furthermore, these peptides also showed excellent potency in mouse models of peritonitis and pneumonia infections caused by carbapenem-resistant A. baumannii. Importantly, both peptides had a high therapeutic index (>25), but caused no significant adverse effects on the liver and kidney functions and the balance of electrolytes in the blood. These peptides can be a promising alternative treatment modality to traditional antibiotics for nosocomial bacterial infections caused by multidrug-resistant Gram-negative bacteria, especially carbapenem-resistant A. baumannii.

Synthesis and antimicrobial activity of β-lactams in dentistry for treatment of root canal infection

Background The treatment of root canal infection consists of eradicating microbes from the root canal and preventing re infection by root filling. Though the existing intra canal medicaments fight against multidrug resistant microbes in root canal, still re-infections occurs. The objective of this study is to synthesize new b-lactam compounds and evaluate their antimicrobial activity to treat root canal infections.

Silver nanoparticles: the powerful nanoweapon against multidrug-resistant bacteria

In the present scenario, pharmaceutical and biomedical sectors are facing the challenges of continuous increase in the multidrug-resistant (MDR) human pathogenic microbes. Re-emergence of MDR microbes is facilitated by drug and/or antibiotic resistance, which is acquired way of microbes for their survival and multiplication in uncomfortable environments. MDR bacterial infections lead to significant increase in mortality, morbidity and cost of prolonged treatments. Therefore, development, modification or searching the antimicrobial compounds having bactericidal potential against MDR bacteria is a priority area of research. Silver in the form of various compounds and bhasmas have been used in Ayurveda to treat several bacterial infections since time immemorial. As several pathogenic bacteria are developing antibiotic resistance, silver nanoparticles are the new hope to treat them. This review discusses the bactericidal potential of silver nanoparticles against the MDR bacteria. This multiactional nanoweapon can be used for the treatment and prevention of drug-resistant microbes.

Nonthermal Atmospheric Plasma Rapidly Disinfects Multidrug-Resistant Microbes by Inducing Cell Surface Damage

Plasma, a unique state of matter with properties similar to those of ionized gas, is an effective biological disinfectant. However, the mechanism through which nonthermal or "cold" plasma inactivates microbes on surfaces is poorly understood, due in part to challenges associated with processing and analyzing live cells on surfaces rather than in aqueous solution. Here, we employ membrane adsorption techniques to visualize the cellular effects of plasma on representative clinical isolates of drug-resistant microbes. Through direct fluorescent imaging, we demonstrate that plasma rapidly inactivates planktonic cultures, with >5 log(10) kill in 30 s by damaging the cell surface in a time-dependent manner, resulting in a loss of membrane integrity, leakage of intracellular components (nucleic acid, protein, ATP), and ultimately focal dissolution of the cell surface with longer exposure time. This occurred with similar kinetic rates among methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, and Candida albicans. We observed no correlative evidence that plasma induced widespread genomic damage or oxidative protein modification prior to the onset of membrane damage. Consistent with the notion that plasma is superficial, plasma-mediated sterilization was dramatically reduced when microbial cells were enveloped in aqueous buffer prior to treatment. These results support the use of nonthermal plasmas for disinfecting multidrug-resistant microbes in environmental settings and substantiate ongoing clinical applications for plasma devices.

Efficacy and safety of nanohybrids comprising silver nanoparticles and silicate clay for controlling Salmonella infection

Developing effective and safe drugs is imperative for replacing antibiotics and controlling multidrug-resistant microbes. Nanoscale silicate platelet (NSP) and its nanohybrid, silver nanoparticle/NSP (AgNP/NSP), have been developed, and the nanohybrids show a strong and general antibacterial activity in vitro. Here, their efficacy for protecting Salmonella-infected chicks from fatality and septicemia was evaluated. Both orally administrated NSP and AgNP/NSP, but not AgNPs alone, effectively reduced the systemic Salmonella infection and mortality. In addition, quantitative Ag analyses demonstrated that Ag deposition from AgNP/NSP in the intestines was less than that from conventional AgNPs, indicating that the presence of NSP for immobilizing AgNPs reduced Ag accumulation in tissue and improved the safety of AgNPs. These in vivo results illustrated that both NSP and AgNP/NSP nanohybrid represent potential agents for controlling enteric bacterial infections.

Characterization of microbial communities distributed in the groundwater pumped from deep tube wells in the Kathmandu Valley of Nepal

Although groundwater is a major water supply source in the Kathmandu Valley of Nepal, it is known that the groundwater has significant microbial contamination exceeding the drinking water quality standard recommended by the World Health Organization (WHO), and that this has been implicated in causing a variety of diseases among people living in the valley. However, little is known about the distribution of pathogenic microbes in the groundwater. Here, we analysed the microbial communities of the six water samples from deep tube wells by using the 16S rRNA gene sequences based culture-independent method. The analysis showed that the groundwater has been contaminated with various types of opportunistic microbes in addition to fecal microbes. Particularly, the clonal sequences related to the opportunistic microbes within the genus Acinetobacter were detected in all samples. As many strains of Acinetobacter are known as multi-drug resistant microbes that are currently spreading in the world, we conducted a molecular-based survey for detection of the gene encoding carbapenem-hydrolysing β-lactamase (bla(oxa-23-like) gene), which is a key enzyme responsible for multi-drug resistance, in the groundwater samples. Nested polymerase chain reaction (PCR) using two specific primer sets for amplifying bla(oxa-23-like) gene indicated that two of six groundwater samples contain multi-drug resistant Acinetobacter.

A systems biology approach to infectious disease research: innovating the pathogen-host research paradigm.

The twentieth century was marked by extraordinary advances in our understanding of microbes and infectious disease, but pandemics remain, food and waterborne illnesses are frequent, multidrug-resistant microbes are on the rise, and the needed drugs and vaccines have not been developed. The scientific approaches of the past—including the intense focus on individual genes and proteins typical of molecular biology—have not been sufficient to address these challenges. The first decade of the twenty-first century has seen remarkable innovations in technology and computational methods. These new tools provide nearly comprehensive views of complex biological systems and can provide a correspondingly deeper understanding of pathogen-host interactions. To take full advantage of these innovations, the National Institute of Allergy and Infectious Diseases recently initiated the Systems Biology Program for Infectious Disease Research. As participants of the Systems Biology Program, we think that the time is at hand to redefine the pathogen-host research paradigm.

Structure pre-requisites for isoflavones as effective antibacterial agents

Recent reports reveal that there is increasing incidence of infections of multidrug-resistant bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). Flavonoids and related compounds have been shown to possess potent antimicrobial activities. Most of the flavonoids are considered as constitutive antimicrobial substances recently termed as “Phytoanticipins,” especially those belonging to prenylated flavonoids and isoflavones. The current review highlights the structure prerequisites for isoflavones as antibacterial agents. Structure–activity relationship (SAR) conclusions have been drawn by comparing the reported minimum inhibitory concentration values for the various isoflavones against S. aureus and MRSA. There exists a significant co-relationship between the presence of certain functional groups (prenyl group, phenolic hydroxyl) at particular positions and antibacterial activity of the compounds. These trends have been postulated with a view of assisting better drug designing of future next-generation antiinfectives, particularly against the bothersome multidrug-resistant microbes. The SAR of these isoflavones has also proved to be a basis to explore the mechanism of antibacterial action. Thus, the study would prove extremely useful to synthesize antibacterial isoflavones in future, which would eventually be beneficial for optimizing the lead molecule for the antibacterial action

Activity of solvent extracts of Prosopis spicigera, Zingiber officinale and Trachyspermum ammi against multidrug resistant bacterial and fungal strains.

The emerging trends of multidrug resistance among several groups of microorganisms against different classes of antibiotics led different researchers to develop efficient drugs from plant sources to counter multidrug resistant strains. This study investigated different solvent extracts of Prosopis spicigera (P. Spicigera), Zingiber officinale, and Trachyspermum ammi (T. ammi) to determine their efficacy against multidrug resistant microbes. Successive extractions of these plants were performed using a Soxhlet apparatus, using solvents with increasing polarities. Preliminary phytochemical analysis was also performed. Minimum inhibitory concentration was determined by a two-fold serial dilution method followed by determination of minimum bactericidal/fungicidal concentration. Multidrug resistant (MDR) strains of Candida albicans, Candida krusei, Candida tropicalis, Candida glabrata, Escherichia coli and reference strains of Streptococcus mutans and Streptococcus bovis were used in the study. The ethanolic fraction of P. spicigera (least minimum inhibitory concentration [MIC] - 4.88 microg/ml) demonstrated a remarkable inhibition of the microorganisms while fractions obtained from those of Zingiber officinale (least MIC-78.125 microg/ml) exhibited little activity. The petroleum ether fraction of T. ammi (least MIC- 625 microg/ml) showed best activity when compared to its other fractions. Qualitative analysis of the phytoconstituents was also performed. The potency shown by these extracts recommends their use against multidrug resistant microorganisms. This study also showed that P. spicigera could be a potential source of new antimicrobial agents.

Antimicrobial activity of five herbal extracts against multi drug resistant (MDR) strains of bacteria and fungus of clinical origin.

Antimicrobial activities of the crude ethanolic extracts of five plants were screened against multidrug resistant (MDR) strains of Escherichia coli, Klebsiella pneumoniae and Candida albicans. ATCC strains of Streptococcus mutans, Staphylococcus aureus, Enterococcus faecalis, Streptococcus bovis, Pseudimonas aeruginosa, Salmonella typhimurium, Escherichia coli, Klebsiella pneumoniae and Candida albicans were also tested. The strains that showed resistance against the maximum number of antibiotics tested were selected for an antibacterial assay. The MDR strains were sensitive to the antimicrobial activity of Acacia nilotica, Syzygium aromaticum and Cinnamum zeylanicum, whereas they exhibited strong resistance to the extracts of Terminalia arjuna and Eucalyptus globulus. Community-acquired infections showed higher sensitivity than the nosocomial infections against these extracts. The most potent antimicrobial plant was A. nilotica (MIC range 9.75-313µg/ml), whereas other crude plant extracts studied in this report were found to exhibit higher MIC values than A. nilotica against community acquired as well as nosocomial infection. This study concludes that A. nilotica, C. zeylanicum and S. aromaticum can be used against multidrug resistant microbes causing nosocomial and community acquired infections.

A medical-grade honey has demonstrated encouraging bactericidal activity, even against multidrug-resistant microbes.

A medical-grade honey has demonstrated encouraging bactericidal activity, even against multidrug-resistant microbes.

Ventilator-associated pneumonia

This review summarises some of the notable papers on ventilator-associated pneumonia (VAP) from January 2003 to October 2004. Ventilator-associated pneumonia remains an important drain on hospital resources. All population groups are affected, but patients with VAP are more likely to be older, sicker, and male, with invasive medical devices in situ. Early VAP diagnosis is desirable to reduce VAP mortality and to retard emergence of multidrug-resistant microbes. This may be possible using preliminary culture results or intracellular organism in polymorphonuclear cells. In most intensive care units, Staphylococcus aureus, Pseudomonas aeruginosa, and Acinetobacter baumannii are the commonest organisms isolated in VAP. However, causative organisms vary between and within hospitals. Consequently, individual intensive care units should develop empirical antibiotic policies to target the pathogenic bacteria prevalent in their patient populations. Preventative strategies aimed at reducing aerodigestive tract colonisation by pathogenic organisms, and also their subsequent aspiration, are becoming increasingly important. Educating medical staff about these simple measures is therefore pertinent. To reduce the occurrence of multidrug-resistant organisms, limiting the duration of antibiotic treatment to 8 days and antimicrobial rotation should be contemplated. Empirical therapy with antipseudomonal penicillins plus beta-lactamase inhibitors should be considered. If methicillin-resistant Staphylococcus aureus VAP is a possibility, linezolid may be better than vancomycin. Prevention remains the key to reducing VAP prevalence.

CONTROL OF ANTIMICROBIAL RESISTANCE IN THE HEALTH CARE SYSTEM

Resistance continues to spread in nosocomial pathogens in acute care hospitals and other key settings of managed health care systems. Appropriate control measures for such resistant organisms depend, in part, on the pathways by which resistance has arisen. Unfortunately, these pathways differ greatly from organism to organism and setting to setting. Although the epidemiology of resistant organisms sometimes is similar to that of susceptible organisms of the same kind, in some situations it may be quite different. This article highlights some of the pathways leading to the development of resistance in bacteria and the relevance of these mechanisms to measures for the control of resistant bacteria in hospital and community settings.

Using host defenses to fight infectious diseases.

In the face of emerging multidrug-resistant microbes, host-defense peptides may provide a unique antibiotic solution.