MRSA, Mersa, Staph, Staff Infection, Treatment & Symptoms

Superbug study shows how quickly drug resistance happens

Superbug study shows how quickly evolution can happen.

And given a few hundred generations of fungus, which happens in weeks, all 120 of their colonies made similar radical changes — though changing a variety of genes to get there. “Basically we traced how the development of a superbug goes,” said Schoustra. “It really matters to you if you’re a drug company. It’s actually bad news.” Danna Gifford, a master’s student in the lab, said that superbug genes have often been seen to have a built-in weakness. Bacteria gain resistance to one drug, but pay for it by sacrificing other genetic strengths. Now this is thrown into question. “Other mutations show up that compensate” for the bug’s loss of vigour, Gifford said. “That’s why (drug) resistance sticks around. OK, they drop in fitness once they become resistant, but then they quickly shoot back up to being high-fitness again.” The study is published in PLoS Biology.

MRSA resistance grows in key drugs

PipelineReview.com - Biotech News & Online Store - ICAAC 2009: promising pipeline presents hope in the battle against MRSA resistance.

Vancomycin is still the most commonly used drug for the treatment of MRSA infections. This intravenous glycopeptide drug was launched by Eli Lilly in the US in 1958. Significant competition to vancomycin finally appeared in 2000 with the launch of Pfizer's Zyvox (linezolid), and later Cubist's Cubicin (daptomycin) in 2004, Wyeth's Tygacil (tigecycline) in 2005 and Theravance/Astellas' Vibatif (telavancin) in 2009. However, the low cost of vancomycin and strong physician familiarity have restricted uptake of these new therapies. Recently though, the old drug's utility against MRSA has increasingly been called into question because of its poor tissue penetration for systemic use, slow bactericidal activity, and the reduced susceptibility of MRSA to the drug: a trend in using higher doses of vancomycin for MRSA infections to respond to the so-called "MIC creep" has consequently seen increased nephrotoxicity in patients. Zyvox (linezolid) is the first and only approved antibiotic from the oxazolidinone class having been launched by Pharmacia (now Pfizer) in the US in 2000. It achieved total sales across the seven major pharmaceutical markets of $968.8 million in 2008 (according to IMS Health), making it the biggest-selling anti-MRSA drug. Unlike its competitors, Zyvox is available in intravenous as well as oral form, giving it a notable advantage. However, the drug's clinical usefulness is now threatened by first case reports of linezolid resistance from a number of countries. At ICAAC, Gomez-Gil and colleagues from Madrid, Spain, reported six cases of linezolid-resistant MRSA affecting critically ill patients (both with and without previous linezolid use) in two surgical intensive care units in their hospital in January 2008. Three of the patients had contracted nosocomial pneumonia, and one subsequently died, with the authors stating that the death seemed to be directly related to the infection.

Researchers observe drug resistance molecular activity

Soon, Superbugs Could be Vanquished! - Page 2.

Although such filaments are known to be crucial to the transmission of antibiotic resistance genes from one bacterium to another, Silverman and Clarke claim that they are the first research team to capture images of the process. For their study, the researchers attached a fluorescent dye to a virus, which in turn bound specifically to the filaments on live bacteria, which allowed the behavior of the filaments to be recorded with a high-powered fluorescence microscope. The group's efforts finally helped it capture a detailed series of images showing filament growth, attachment to other cells, and retraction to pull the cells together in preparation for genetic transfer. "This is an important step forward in understanding how antibiotic resistance spreads," said Silverman.

Linezolid Resistance Emerging

Common staph germs getting stronger, more widespread | ajc.com.

Doctors from Spain reported the first hospital outbreak of MRSA resistant to linezolid, a last-resort drug sold by Pfizer Inc. as Zyvox in the United States and Zyvoxid in Europe. A dozen intensive care patients got pneumonia and bloodstream infections last spring and the outbreak was controlled after use of the antibiotic was severely curbed, said Dr. Miguel Sanchez of Hospital Clinico San Carlos in Madrid.

Key Ways to Measure Drug-Resistant Infections in Healthcare

Link: Key Ways to Measure Drug-Resistant Infections in Healthcare.

Healthcare experts today published a position paper that provides strategies that healthcare facilities can use to monitor trends in the occurrence of emerging drug-resistant pathogens and determine the impact of local intervention efforts. “Recommendations for Metrics for Multidrug-Resistant Organisms (MDROs) in Healthcare Settings: SHEA/HICPAC Position Paper,” published online on Sept. 23 in the journal Infection Control and Hospital Epidemiology, aims to help healthcare facilities standardize monitoring of these and other dangerous pathogens within their particular institutions so that infection prevention and control teams can quickly recognize new resistance profiles and protect vulnerable patient populations.

Resistance Trends Stable in UK

Link: Non-susceptibility trends among staphylococci from bacteraemias in the UK and Ireland, 2001-06 -- Hope et al. 62 (2): ii65 -- Journal of Antimicrobial Chemotherapy.

Results: One thousand four hundred and forty-eight S. aureus and 1214 CoNS were collected. The overall prevalence of methicillin resistance was 42% (with ≤6% annual fluctuation) for S. aureus and 67% (range 54% to 80%) for CoNS. Resistance to aminoglycosides, macrolides, quinolones and tetracyclines was strongly associated with methicillin resistance in both species groups. Many (20.8%) CoNS and three (0.2%) S. aureus isolates were non-susceptible to teicoplanin, but there was no vancomycin non-susceptibility found in S. aureus and only one vancomycin-intermediate CoNS isolate. There was little evidence of susceptibility trends over time for any antibiotic, with the surveillance period preceding the recent fall in methicillin-resistant S. aureus (MRSA) prevalence indicated by the mandatory surveillance of MRSA bacteraemia in England. The newer antibiotics, ceftobiprole, daptomycin, linezolid, telavancin and tigecycline, all had excellent activity against staphylococci. Conclusions: Multiresistant staphylococci remain abundant in the UK and Ireland but many new antimicrobials are becoming available and these may prove effective alternatives to glycopeptides.

Antibiotic consumption in needs chenge worldwide

Link: Antibiotic consumption in southern and eastern Mediterranean hospitals: results from the ARMed project -- Borg et al. 62 (4): 830 -- Journal of Antimicrobial Chemotherapy.

The median total antibiotic use during the study period was 112 defined daily doses per 100 bed-days (DDD/100BD), with an inter-quartile range of 84–428 DDD/100BD. The most common antibiotic groups prescribed were the extended-spectrum and combination penicillins, first- and third-generation cephalosporins and quinolones. Overall, a predominant consumption of wide-spectrum agents was noted, with a significant correlation between the levels of use of third-generation cephalosporins and carbapenems. Conclusions: Emphasis on wide-spectrum agents could explain one possible factor behind the documented high prevalence of resistance in important pathogens within these same hospitals and suggests the need for improved antibiotic stewardship and prescribing programmes, which may well be applicable to the whole region.

The drrug for when all else fails

Link: Enanta Initiates Phase 1 Study On EDP-322, An Oral Antibiotic With Activity Against Hospital- And Community-Acquired MRSA.

Enanta Pharmaceuticals, a leader in the development of small molecule anti-infective drugs, announced today the initiation of a Phase 1 study on investigational oral antibiotic EDP-322, a first-in-class MRSA-active Bicyclolide, a novel macrolide-related drug class with a distinct resistance profile. The clinical development program for EDP-322 will include the treatment of hospital- and community-acquired gram-positive infections, including methicillin-resistant Staphylococcus aureus (MRSA). Preclinically, EDP-322 has demonstrated strong in vitro activity against hospital-acquired MRSA strains resistant to vancomycin, Zyvox(R) (linezolid), and CUBICIN(R) (daptomycin).

Predictors of high vancomycin MIC values among patients with MRSA

Link: Predictors of high vancomycin MIC values among patients with methicillin-resistant Staphylococcus aureus bacteraemia -- Lodise et al., 10.1093/jac/dkn329 -- Journal of Antimicrobial Chemotherapy.

Background: Recent evidence suggests that vancomycin demonstrates reduced activity against methicillin-resistant Staphylococcus aureus (MRSA) infections when vancomycin MIC values are at the high end of the susceptibility range (≥1.5 mg/L). However, scant research exists on factors predictive of high vancomycin MICs (≥1.5 mg/L) among MRSA bacteraemic patients. Empirical therapy decisions would greatly benefit from such information. Objectives: To identify the parameters predictive of high vancomycin MICs (≥1.5 mg/L) among MRSA bacteraemic patients and to develop an evidence-based clinical prediction tool. Methods: This observational cohort study included adult patients with MRSA bloodstream infections between January 2005 and May 2007. Demographics, co-morbid conditions, and microbiology and antibiotic exposure data were collected. Vancomycin MICs were determined by Etest. Stepwise logistic regression was used to identify independent predictors of high vancomycin MICs. Results: Of the 105 patients who met the inclusion criteria, 77 patients (73.3%) exhibited a high vancomycin MIC (≥1.5 mg/L). In the bivariate analysis, prior vancomycin exposure within 30 days of index culture collection [15 patients (19.5%) versus 1 patient (3.6%), P = 0.05] and residence in an intensive care unit (ICU) at the onset of infection [27 patients (35.1%) versus 3 patients (10.7%), P = 0.02] were both significantly associated with a high vancomycin MIC value and both were independent predictors of high MICs in the logistic regression. Conclusions: Patients with MRSA bloodstream infections in the ICU or with a history of vancomycin exposure should be considered at high risk of infection with strains for which vancomycin MICs are elevated. Appropriate and aggressive empirical therapy is required for these patients.

Vancomycin: Resistance Emerging

Link: Methicillin-Resistant Staphylococcus aureus Infection With Intermediate Sensitivity to Vancomycin: A Case Report and Literature Review -- Schairer et al., 10.1177/0885066608320849 -- Journal of Intensive Care Medicine.

Staphylococcus aureus is a major cause of bacteremia and endocarditis in adults. Vancomycin is the standard therapy for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. Although clinical failure associated with the development of reduced susceptibility to vancomycin during the course of treatment for MRSA bacteremia has been reported infrequently, such an occurrence is very serious. We report a case of 43-yearold woman with of MRSA bacteremia, who relapsed after initial, apparently successful vancomycin treatment and developed left-sided endocarditis and vertebral osteomyelitis. Two weeks into her second admission, the vancomycin minimal inhibitory concentration rose from ≤ 2 µg/mL (susceptible) to 4 µg/mL (intermediate). The antibiotic was changed to daptomycin. Subsequent blood cultures were negative and sepsis resolved.

The growing burden of antimicrobial resistance

Link: The growing burden of antimicrobial resistance -- Hawkey 62 (1): i1 -- Journal of Antimicrobial Chemotherapy.

Since the first usage of antimicrobials, the burden of resistance among bacteria has progressively increased and has accelerated within the last 10 years. Antibiotic resistance genes were present at very low levels prior to the introduction of antibiotics and it is largely the selective pressure of antibiotic use and the resulting exposure of bacteria, not only in humans but also in companion and food animals and the environment, which has caused the rise. The increasing mobility across the globe of people, food and animals is another factor. Examples of this are the international pandemic of different genotypes of CTX-M extended-spectrum β-lactamases (particularly CTX-M-14 and -15) and the emergence of the carbapenemase KPC-1 in both the USA and Israel. This review details examples of both the emergence and dissemination through different genetic routes, both direct and indirect selective pressure, of significance resistance in Staphylococcus aureus, Enterococcus species, Enterobacteriaceae and Pseudomonas/Acinetobacter. The response made by society to reduce resistance involves surveillance, reduced usage, improved infection control and the introduction of new antimicrobial agents. Although efforts are being made in all these areas, there is an urgent need to increase the effectiveness of these interventions or some bacterial infections will become difficult if not impossible to treat reliably.

Pre-Op Action Over MRSA - More Precision Needed

CURRENT TRENDS IN ANTIBIOTIC RESISTANCE IN ELECTIVE ORTHOPAEDICS. -- Ollivere et al. 90-B (2): 297 -- The Journal of Bone and Joint Surgery (Proceedings).

Results: We found a positive correlation between previous urine infection, MRSA status, revision surgery, and diabetes and wound infection. Nearly 35% of bacterium cultured were cephalosporin resistant, and 12% demonstrated multiple antibiotic resistance. Discussion: It is good clinical practice to provide antibiotic prophylaxis in joint replacement, but the blind use of cephalosporins in all patients does not make sense because of increased incidence of antibiotic resistant bacteria. We present evidence based guidelines for the use of antibiotic prophylaxis in elective orthopaedic surgery and empirical antibiotic treatment in patients with wound infection before culture results are available.

Patients' perspectives of antibiotic resistance and MRSA

Link: Towards a better understanding of patients' perspectives of antibiotic resistance and MRSA: a qualitative study -- Brooks et al., 10.1093/fampra/cmn037 -- Family Practice.

There was uncertainty concerning the nature and implications of antibiotic resistance for both individuals and the wider community. While some patients viewed antibiotic resistance as a problem for society, most did not see it as something that would affect them personally. Many thought that science would provide the solution through the development of new drugs. Responsibility for antibiotic resistance was mostly attributed to ‘other’ patients and GPs who had respectively overused and overprescribed antibiotics in the past. As MRSA was mainly seen as a hospital-based problem, blame was largely directed at hospital management and, to a lesser degree, doctors, nurses and cleaners. Concerns about antibiotic resistance were not regarded as a reason to modify individual use of antibiotics. Conclusions. Many primary care patients are unaware of what antibiotic resistance is and how it arises. The causes of, and responsibility for, antibiotic resistance are usually attributed to external rather than personal factors and patients perceive that its solutions are outside of their control.

How Vancomycin resistance grows

Link: Genomics Reveals a Point Mutation in the Two-Component Sensor Gene graS that Leads to Vancomycin-Intermediate Resistance in Clinical Staphylococcus aureus -- Howden et al., 10.1128/AAC.01613-07 -- Antimicrobial Agents and Chemotherapy.

We studied a vancomycin susceptible clinical MRSA isolate (MIC 1 µg/ml), and compared it with an isogenic blood culture isolate from the same patient despite 42 days of vancomycin treatment (MIC 4 µg/ml). A whole-genome sequencing approach allowed near complete assembly of the genome sequences of the two isolates and revealed only six nucleotide substitutions in the VISA strain when compared with the parent. One mutation occurred in graS, encoding a putative two-component regulatory sensor, leading to a change from a polar to a non-polar amino acid (T136I) in the conserved histidine region of the predicted protein. Replacing the graS allele of the vancomycin susceptible parent strain with the graS allele from the VISA derivative resulted in increased vancomycin resistance at a level between the VSSA and VISA clinical isolates, confirming a role for graRS in VISA. Our study suggests that MRSA is able to develop clinically significant vancomycin resistance via a single point mutation and the two-component regulatory system graRS is a key mediator of this resistance. However, additional mutations are likely required to express the full VISA phenotype.

Right Initials - Wrong Name for MRSA?

Link: HighWire Press -- Medline Abstract.

RESULTS: Four thousand four hundred and fifty-five isolates providing from 3602 patients were identified between 2001 and 2006. MRSA rate and incidence for 1000 hospitalization-days significantly decreased from 34.7 to 22.6% and 1.3 to 0.6% respectively (p<0.001). Significant decrease was observed for multiresistant MRSA (72.9 to 46.3%, p<0.001), while no change was observed for multiresistant MSSA (2.9 to 3.4%). Among the 186 different antibiotic patterns isolated, four MRSA-phenotypes significantly decreased whereas two MSSA-phenotypes significantly increased. The main MRSA phenotype, resistant to kanamycin, tobramycin, macrolides-lincosamides-streptograminesB, and fluoroquinolones, significantly decreased from 11.9 to 5.9% (p<0.001). Glycopeptide Intermediate S. aureus (GISA) phenotypes disappeared. CONCLUSION: At this date, methicillin remains in our institution a relevant marker of multiresistance but trend is changing.

MRSA Drug Resistance Patterns in the USA

Link: Susceptibility of Staphylococcus aureus isolated from skin and wound infections in the United States 2005-07: laboratory-based surveillance study -- Tillotson et al. 62 (1): 109 -- Journal of Antimicrobial Chemotherapy.

Results: There were over 380 000 isolates of S. aureus tested and reported for the period 2005–07. Methicillin resistance was observed in 57.8% in 2007, with little change from 2005. There was little difference in rates of methicillin resistance between community and hospital strains, although strains from intensive care units (ICUs) tended to be slightly more resistant overall. Resistance to other antimicrobials was also reported. A regional variation in resistance rates was noted with the highest rates in the Central states and lowest in the New England and Mid-Atlantic regions. There was high activity observed with trimethoprim/sulfamethoxazole and gentamicin. Linezolid resistance was rare. Oxacillin resistance was similar among paediatric and elderly cohorts, whereas ciprofloxacin and clindamycin resistance was significantly (P < 0.01) more common in elderly patients when compared with both paediatric and adult populations. Less than a third of all isolates showed no resistance mechanism, 30.3%. Three distinct resistance phenotypes accounted for 46% of all resistant strains. Overall, there were more highly drug-resistant isolates from the ICU with four, five or six drug-resistant phenotypes accounting for over a third of all strains. Conclusions: S. aureus has become methicillin-resistant in both the community and hospital settings; however, little change has been seen in the past 3 years. Multiresistant strains now are seen in all settings, but due to regional variation, empirical therapy should be guided by local susceptibility patterns. Currently, among the agents studied, only trimethoprim/sulfamethoxazole, gentamicin and linezolid exhibit susceptibility rates of >95%.

Stronger dose Vancomycin need growing

Link: HighWire Press -- Medline Abstract.

A greater rate of treatment failures with vancomycin in methicillin-resistant Staphylococcus aureus (MRSA) bacteremia has been reported recently when the minimum inhibitory concentration (MIC) is >/= 2 mg/l. This study has aimed to evaluate if there are clinical and/or epidemiological factors that predict isolation of a MRSA strain with MIC of vancomycin of >/=2 mg/L in the bacteremia episodes collected during a 15 year period (January 1991 to December 2005) in a tertiary urban hospital. During the study period, a total of 478 episodes of MRSA bacteremia were studied prospectively. The following clinical variables were recorded for each one: age, gender, comorbidity, previous administration of vancomycin or another antibiotic, prognosis of baseline diseases, bacteremia focus, shock, empiric antibiotic received and mortality. The MIC of vancomycin of 419 strains (88%) was determined with the E-test. In 216 (52%) of the isolations the MIC of vancomycin was 1.50 mg/L, in 110 (26%) of the cases it was /=2 mg/l regarding the MIC strains /= 2 mg/l was significantly greater than those isolated with MIC /=2 mg/l was the nosocomial-acquired infection OR (95 % CI): 1.94 (1.04-3.63); p=0.04. Although the isolation of a MRSA strain with MIC of vancomycin >/=2 mg/l is more frequent in the nosocomial-acquired bacteremia episodes, in the clinical practice, it is not a useful predictive parameter because the frequency of isolation of these strains in the community is also high. Key words: Methicillin-resistant S. aureus bacteremia. Decrease sensitivity to vancomycin. Predictive factors. Empiric treatment of methicillin-resistant S. aureus bacteremia. Rev Esp Quimioter 2008;21(2):93-98.

Vancomycin losing it's punch

Link: HighWire Press -- Medline Abstract.

Vancomycin use has increased dramatically worldwide since the mid-1980s, largely as a result of empirical and directed therapy against burgeoning methicillin-resistant Staphylococcus aureus (MRSA) infections. With limited choices, clinicians have traditionally relied on vancomycin alone in the management of serious MRSA infections and have enjoyed a significant period free of vancomycin resistance in S. aureus. Even now, 5 decades after its introduction, vancomycin resistance among S. aureus strains, as currently defined microbiologically, remains rare. Yet it is becoming clear that vancomycin is losing potency against S. aureus, including MRSA. Serious infections due to MRSA defined as susceptible in the laboratory are not responding well to vancomycin. This is demonstrated by increased mortality seen in patients with MRSA infection and markedly attenuated vancomycin efficacy caused by vancomycin heteroresistance in S. aureus. Therefore, it appears that our definition of vancomycin susceptibility requires further scrutiny as applied to serious MRSA infections, such as bacteremia and pneumonia.

Sugar coating could help roll back resistance

Link: Improved Targeting Using Sugar-Coated Antibiotics.

Researchers from the John Innes Centre and the University of East Anglia have recently elucidated the structure and function of an enzyme which is involved in decorating antibiotics with sugar molecules. Many antibiotics have a variety of different carbohydrate molecules attached to them which can help the antibiotic to be taken up by the target organism or overcome resistance. By manipulating the sugar, it may be possible to restore usefulness in antibiotics to which resistance has developed.

Antibiotic stewardship vital

Link: HighWire Press -- Medline Abstract.

PURPOSE: To address how the high endemic levels of antimicrobial resistance and multidrug resistance in hospitals have challenged clinicians to select appropriate therapy for effectively treating bacterial infections among seriously ill patients. SUMMARY: Among gram-positive bacterial infections, differentiating between healthcare-associated and community-associated methicillin-resistant Staphylococcus aureus infections is becoming more difficult and can seriously impact therapeutic strategies and hence outcomes. Furthermore, the rising prevalence of multidrug-resistant gram-negative bacterial infections is increasing the pressure on proper antimicrobial selection given the dearth of new antimicrobial agents under development. Optimized dosing strategies will be instrumental in minimizing emergence of resistance and preserving the utility of currently available agents. Antimicrobial stewardship programs in conjunction with stringent infection control policies will be critical in improving the appropriate use of antimicrobials while reducing the spread of nosocomial pathogens. CONCLUSION: Addressing the challenges of antimicrobial resistance in hospitals will require a multidisciplinary approach, with clinical pharmacists taking a proactive role in ensuring the appropriate use of antimicrobials.