Saturday, October 17, 2009

MRSA presents a growing danger

MRSA presents a growing danger

October 14, 2009

"World MRSA Day” was celebrated this month. What are Onslow Memorial Hospital, Onslow Health Department, Onslow Caring Community Clinic, local doctors and nurses, Onslow schools, Coastal Carolina Community College, as well as local, state, and federal government officials, television and newspapers doing to educate the public about this deadly disease?

I don’t have an answer, do you?

MRSA is an acronym for methicillin-resistant staphylococcus aureus. It has been described as “Superbug” because it is resistant to most antibiotics. The disease can cause deadly infections in patients in health care facilities and in the community. The disease can enter through cuts and abrasions in the skin and some research investigators believe it can enter just through the skin alone just by touching contaminated surfaces and items or skin-to-skin contact with someone who is colonized with MRSA.

MRSA can be transmitted sexually or by a handshake. It can cause skin infections that may look like a spider bite, a pimple, rash or a boil and even large abscesses. They may appear red, swollen, painful or have pus or other drainage. Some people may have chills and fever, feel nauseous and acute pain. In serious cases, the patient may feel lethargic (fatigue) and headaches.

MRSA infections can cause other ranges of symptoms depending on the part of the body that is infected, such as bloodstream infections, pneumonia and urinary tract infections. It may also enter the bone marrow, causing osteomyelitis, and destroy heart valves, causing endocarditis. And it can cause septicemia, toxic shock and death.

The disease is easily spread in areas where people share crowded living conditions such as hospitals, nursing homes, schools, gyms, military barracks, prisons and call centers, but it can also be contracted anywhere people share items. Anyone of any age can be infected.

Approximately 2 percent of the U.S. population is now colonized with MRSA, which means they are carrying the infection in their bodies.

Unfortunately, the cases of MRSA are not being recorded in most states as they should be. In North Carolina, the N.C. Communicable Disease Manual states that individual MRSA infections are not reportable under N.C. law; however, outbreaks, defined as two or more cases linked in time and place, should be investigated by the local health director if they represent a significant threat to the public health. Also, colonization surveys are time and resource intensive and are not generally necessary to direct control or prevention efforts. In short, North Carolina thinks it costs too much to keep accurate records. Other states may think similarly; however, the CDC has been able to get enough information to record that this deadly disease killed 18,650 people in the U.S., compared to 16,000 people who died from AIDS in 2005.

There is no vaccine, or cure, but there is some treatment, which may not last since the disease has mutated into at least 16 strains and some reports say it may be about to become an airborne disease. Also, there is research going on about the disease, but since it has been around since 1960 and with lack of reporting of cases and lack of knowledge about the disease, many people will continue dying from MRSA.

Until the medical research community and funding for such research decides to commit to education and research to eliminate MRSA, instead of such things as finding the latest erectile dysfunction pill, the public will continue suffering from this epidemic and we are left with what seems to be the be-all and end-all of treatment — the phrase “wash your hands.”

Maybe Tony Shalhoub’s Adrian Monk character is not as crazy as people think.

Jimmy E. Gay


Innate immunity as a key element in host defense against methicillin resistant Staphylo-coccus aureus.

Innate immunity as a key element in host defense against
methicillin resistant Staphylo-coccus aureus.

Section of Infectious Diseases, Children's Mercy Hospital and, Clinics University of Missouri at Kansas City Kansas City, MO, USA

Methicillin resistant Staphylococcus aureus (MRSA) is a frequent reason for healthcare visits. Both pathogen and host differences likely are factors in determining the frequency of recurrent MRSA infections in otherwise normal hosts.

Among such host factors are altered innate immune responses in skin and soft tissues. This review examines four selected processes of the innate immune system by which the host may prevent MRSA skin or soft tissue infections. The first involves cationic antimicrobial peptides (CAMPs) found in skin, skin organs, and leukocytes. The second requires chemotactic molecules secreted by monocytes and their derivatives. The third is CRP, a primitive opsonin and activator of complement. And the fourth includes neutrophil defenses. These last include the traditional phagocytic bacterial killing by intact neutrophils.

This is an intracellular killing accomplished by reactive oxygen species (ROS), CAMPs, and microbicidal enzymes. A second recently described neutrophil defense results in extracellular killing using neutrophil extracellular traps (NETs), NETs are produced as neutrophils lyse by a process known as NETosis. The balance between these and similar innate immune responses and bacterial virulence factors likely determines whether MRSA colonization/exposure results in infection of skin or soft tissue.

Minerva Pediatrica

A comparison of linezolid with glycopeptides in severe MRSA pneumonia.

A comparison of linezolid with glycopeptides in severe MRSA pneumonia.

Division of Pulmonary and Critical Care Medicine, University of Connecticut Health Center, Farmington, CT 06030-1225, USA.

Evaluation of: Luna CM, Bruno DA, García-Morato J et al. Effect of linezolid compared with glycopeptides in methicillin-resistant Staphylococcus aureus severe pneumonia in piglets. Chest 135(6), 1564-1571 (2009). Methicillin-resistant Staphylococcus aureus (MRSA) has emerged as a major pathogen in nosocomial infections and accounts for a large proportion of nosocomial pneumonia. However, there are limited antibiotics available for the treatment of this serious and potentially lethal infection. Until recently, the only effective antibiotic was vancomycin, but the oxazolidinones, such as linezolid, have been shown to be a valuable addition to the arsenal of antimicrobial agents that can be used for MRSA pneumonia.

Clinical trials have been conducted to compare vancomycin and linezolid head-to-head in pneumonia and, in post hoc subgroup analyses, showed that linezolid use was associated with improved survival. The ensuing debate over these results was dominated by two opinions; there were those who speculated on the mechanism by which linezolid achieved this benefit, namely attributing it to pharmacodynamics and pharmacokinetics, and others who criticized the methodology of the studies and questioned the validity of the results altogether.

This study by Luna and colleagues was designed with several goals in mind. The first was to attempt to generate an animal model of MRSA pneumonia in piglets by duplicating techniques used in animal models of Gram-negative pneumonia. Then they studied the effect of three antibiotics (vancomycin, linezolid and teicoplanin) on outcomes in the same model, while simultaneously measuring antibiotic levels in the serum, bronchoalveolar lavage fluid and lung tissue, in an attempt to attribute differences in survival to pharmacological properties of the drugs used.

Their results showed a survival benefit only for linezolid, despite the fact that all three antibiotics had levels above MIC in all the compartments sampled, leading them to speculate that linezolid may have improved outcomes by mechanisms not directly related to its antimicrobial actions.

Expert Reviews

Methicillin resistant Staphylococcus aureus: carriage rates and characterization of students in a Texas university.

Methicillin resistant Staphylococcus aureus: carriage rates
and characterization of students in a Texas university.

Clin Lab Sci. 2009 Summer

Clinical Laboratory Science, Texas State University-San Marcos, San Marcos, TX 78666-4616, USA.

OBJECTIVE: To evaluate the carriage rates of Staphylococcus aureus and methicillin resistant Staphylococcus aureus (MRSA) in a university student population and describe risk factors associated with the carriage of each. DESIGN: Cross-sectional study (N = 203). Institutional Review Board approval was obtained from Texas State University-San Marcos.

SETTING: Texas State University-San Marcos, San Marcos, TX.

PARTICIPANTS: Two-hundred and three university student samples were collected from December 2007 to July 2008.

INTERVENTIONS: None indicated.

MAIN OUTCOME MEASURES: The sample set was screened for S. aureus and MRSA identification by standard microbiological techniques and confirmed by use of a Vitek 2 per manufacturer recommendation. Antibiotic susceptibility testing was conducted on each MRSA isolate by Vitek 2. A questionnaire was conducted with each student to acquire demographic and risk factor information. Demographic data is shown by raw numbers, percentages, mean, and median where applicable. The compiled data was screened and analyzed by chi square (p values) and odds ratio (OR) with confidence interval (CI) to determine significance.

RESULTS: Of the 203 participants who were screened, 60 (29.6%) carried S. aureus. Univariate analysis found that only hospitalization in the past 12 months was significantly associated with the risk of being a S. aureus carrier (OR=3.0, 95% CI 1.28-7.03). Of the 60 participants that carried S. aureus, 15 were identified as MRSA. This relates to a 7.4% MRSA carriage rate among generally healthy university students. Univariate analysis found that hospitalization in the past 12 months (OR = 4.2, 95% CI 1.29-13.36) and recent skin infection (OR = 4.4, 95% CI 1.07-18.24) were significantly associated with the risk of being a MRSA carrier. No unique antibiotic susceptibility patterns were identified with the MRSA isolates.

CONCLUSIONS: The carriage rate of S. aureus is consistent with similar studies. MRSA carriage in this university study appears high as compared to the general population. Although this study did not confirm a variety of risk factors for carriage of MRSA previously identified by others, university healthcare personnel should be aware of the changing epidemiology of MRSA and preventive measures needed to avoid outbreaks.

PMID: 19827412 [PubMed - in process]

Genetic Analysis of High-Level Mupirocin Resistance in ST80 clone of Community-Associated Methicillin-Resistant Staphylococcus aureus.

Genetic Analysis of High-Level Mupirocin Resistance in ST80 clone of
Community-Associated Methicillin-Resistant Staphylococcus aureus.

J Med Microbiol. 2009 Oct 15

Kuwait University.

Four Community- associated MRSA isolates expressing high-level mupirocin resistance (MIC: greater then1024mg/L) were isolated from four sites of a diabetic patient and characterized for the genetic location of their resistance determinants and typed using pulsed-field gel electrophoresis (PFGE), SCCmec coagulase gene and multilocus sequence typing to ascertain their relatedness. The presence of genes for resistance to high-level mupirocin (mupA), tetracycline (tetK) and fusidic acid (far 1), Panton-Valentine leukocidin (PVL), accessory gene regulators (agr) and capsular polysaccharide (cap) were detected in PCR assays. They were resistant to kanamycin, streptomycin, tetracycline, fusidic acid and cadmium acetate. They harboured mupA, tetK, far1, PVL, agr 3 and cap8.

They had identical PFGE pattern, coagulase gene type, possessed type IV SCCmec element and belonged to sequence type 80 (ST80). In contrast, they had three different plasmid profiles consisting of (1) 28.0 and 26.0 kb, (2) 28.0, 21.0 and 4.0 kb, (3). 41.0 and 4.0 kb. Genetic studies located resistance to tetracycline, fusidic acid and cadmium acetate on the 28 kb plasmids and mupA on related non conjugative 26 kb and 21 kb plasmids. One of the 21-kb mupirocin resistance plasmids was derived from the 41 kb plasmid during transfer experiments. The emergence of high-level mupirocin resistance in ST80-SCCmec-IV MRSA clone demonstrates the increasing capacity of CA-MRSA clones to acquire resistance to multiple antibacterial agents.

The presence of different plasmid profiles in genetically identical isolates created difficulty in interpretation of typing results and highlighted the weakness of using plasmid analysis as a sole method for strain typing.

PMID: 19833783 [PubMed - as supplied by publisher]

Sunday, October 11, 2009

Methicillin-resistant Staphylococcus aureus (MRSA) in the Athlete.

Methicillin-resistant Staphylococcus aureus (MRSA) in the Athlete.

D. E. RedziniakD. R. DiduchK. TurmanJ. HartT. L. GrindstaffJ. M. MacKnightD. J. Mistry

The Orthopedic and Sports Medicine Center, Department of Orthopedic Surgery, Annapolis 21409, USA.

Although once considered only a nosocomial pathogen, methicillin-resistant Staphylococcus aureus (MRSA) is a rapidly emerging, problematic infection in the community. Community acquired MRSA (CA-MRSA) is notably becoming more prevalent in athletic environments and unfortunately, can be easily transmitted via superficial abrasions and minor skin trauma. CA-MRSA infections are highly contagious and are associated with significant morbidity, with published reports of up to 70% of infected team members requiring hospitalization and intravenous antibiotics . Risk factors for athletic related environments include contact sports with repeated close physical contact with other competitors, open abrasions, and sharing of personal equipment. Failure to correctly diagnose and appropriately treat skin and soft tissue lesions infected with CA-MRSA may contribute to large scale MRSA infections in athletic environments. The purpose of this review article is to help sports medicine physicians prevent, identify, and treat MRSA skin and superficial soft tissue infections in athletic environments. Georg Thieme Verlag KG Stuttgart New York.

Thieme Connect

MRSA survivors say screening is key

MRSA survivors say screening is key

Special to the Tribune

October 7, 2009

Ken Reimer's activism began when his infant daughter, Madeline, died after contracting a mysterious illness.

In Jeanine Thomas' case, doctors almost amputated her leg. Debbie Holsten spent nearly $150,000 recovering from a superbug.

This month, Reimer, Thomas and Holsten are speaking up about the dangerous bacterium that caused them so much pain. They are among a passionate group of local activists urging more action to stem the spread of methicillin-resistant Staphylococcus aureus, or MRSA.

MRSA survivors gathered last week at Loyola University's downtown campus to observe the first-ever World MRSA Day, which kicked off MRSA Awareness Month to spread the word about a dangerous infection.

"It shatters people's lives," said Thomas, a Willowbrook resident who is founder of the MRSA Survivors Network and was bedridden for months while recovering from the damage caused by MRSA.

"The media and the government like the disease du jour," said Dr. William Jarvis, an
based infectious disease specialist who has studied the spread of MRSA. "I think the time has come for our government to spend sufficient resources to stop MRSA infections."

When compared with much-publicized diseases such as SARS and swine flu, Jarvis and others say the dangers of MRSA demand a stronger response.

The federal Centers for Disease Control and Prevention consider MRSA a "major public health problem" and estimate that 19,000 people die from MRSA in the United States each year. Fewer than 15,000 die annually from HIV/AIDS.

MRSA first appeared in American hospitals in the late 1970s, and the threat has grown exponentially since then. The disease comes in two forms: community-associated MRSA and the more common hospital-associated disease. MRSA is contracted by contact with items where the bug may reside, such as playgrounds, medical utensils, doctors' jackets or even other people's skin. It often enters the body through cuts or during surgery.

MRSA is tougher to treat than other staph infections because it is resistant to many antibiotics, as the name suggests. It's unclear how widespread the problem is in
Chicago and Illinois, but 1.2 million MRSA infections were documented nationwide in 2006.

Illinois was the first state to require hospitals to report infection rates, but the state health department has yet to release the numbers. At least 25 other states publish the data. A Web site with statistics from 2008 is expected to launch sometime this month, said Illinois Department of Public Health spokeswoman Kelly Jakubek.

State legislation mandates that all hospitals screen at-risk patients and those entering intensive care units, but Thomas said all patients should be screened.

"It's about saving lives," she said. Thomas said she may push for broader legislation for MRSA screening.

At Loyola University Hospital in Maywood, where all patients have been screened since late 2007, the number of hospital-associated MRSA cases has dropped by two-thirds, said Dr. Jorge Parada, associate professor of medicine, infectious diseases, at the
Loyola University Chicago Stritch School of Medicine.

Parada said Loyola saw a 566 percent jump in patients coming to the emergency room with MRSA from 2000 to 2007 and, once it began universal screening, found one in every 14 patients was already colonized with MRSA upon admission. Those found to be infected are isolated and treated.

"Without looking for MRSA, all we see is the tip of the iceberg," he said.

Still, activists' efforts won't bring Reimer's daughter back.

MRSA devastated Reimer and his wife, Beth. The
Batavia couple lost their newborn, Madeline, to the disease. A second daughter, Emma, was diagnosed with the bacterium shortly after her birth but survived.

"We were trying to figure out how a healthy baby girl dies from something we've never heard of, a superbug," Reimer said. "These are two babies that didn't do anything wrong."

Chicago Tribune Health

Tuesday, September 29, 2009

Microbiology of drugs for treating multiply drug-resistant Gram-positive bacteria.

Microbiology of drugs for treating multiply drug-resistant Gram-positive bacteria

J Infect. 2009 Sep

Division of Infectious Diseases, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA.

George M. EliopoulosCorresponding Author Contact Information, a, E-mail The Corresponding Author

Several new antimicrobials demonstrate in vitro activity against methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), and other Gram-positive bacteria. Data from large surveys indicate that linezolid, daptomycin, and tigecycline are almost universally active against MRSA. Linezolid and tigecycline inhibit both Enterococcus faecium and Enterococcus faecalis at low concentrations; daptomycin is somewhat more potent against the latter. The investigational agents dalbavancin and telavancin are more potent than vancomycin against vancomycin-susceptible organisms. Dalbavancin inhibits vanB type VRE at low concentrations, but is not active against vanA type VRE. Telavancin is less active against VRE than against vancomycin-susceptible enterococci, but minimum inhibitory concentrations are lower than those of vancomycin against VRE. With continued careful use of available antimicrobials, the vast majority of these organisms should remain susceptible to 1 or more of the agents discussed for the foreseeable future.

ScienceDirect/Trends in Microbiology

Treatment options for nosocomial pneumonia due to MRSA.

Treatment options for nosocomial pneumonia due to MRSA.

J Infect. 2009

Department of Medicine, Winthrop University Hospital, Mineola, New York, USA. Michael S. NiedermanCorresponding Author Contact Information, a, b, E-mail The Corresponding Author

Keywords: Antibiotic resistance; Nosocomial pneumonia; Guidelines; MRSA; De-escalation therapy

Nosocomial pneumonia, which includes hospital-acquired pneumonia, ventilator-associated pneumonia, and health care associated pneumonia, remains an important cause of morbidity and mortality. The continuing emergence of methicillin-resistant Staphylococcus aureus (MRSA) as a nosocomial pneumonia pathogen is particularly problematic not only because of its prevalence, but also because antimicrobial resistance is increasingly associated with inappropriate empirical antibiotic therapy. As a result, intensivists are faced with the dual goals of providing initial accurate broad-spectrum antibiotic coverage to reduce mortality while minimizing the risk for the emergence of antimicrobial resistance. These competing goals can be achieved by using an approach that initially delivers liberal broad-spectrum coverage followed by de-escalation once culture results and serial clinical observations become available. In ventilator-associated pneumonia, linezolid has demonstrated favorable activity against Gram-positive bacteria, including MRSA, and is recommended in evidence-based guidelines as an alternative to vancomycin, particularly when MRSA is documented as the etiology.

Elsevier/Science Direct

Monday, September 21, 2009

Short communication: methicillin-resistant Staphylococcus aureus detection in US bulk tank milk.

Short communication: methicillin-resistant Staphylococcus aureus detection in US bulk tank milk.
J Dairy Sci. 2009 Oct

Virgin JE, Van Slyke TM, Lombard JE, Zadoks RN.
USDA, APHIS, VS, Centers for Epidemiology and Animal Health, Fort Collins, CO 80526-8117, USA.

* USDA:APHIS:VS, Centers for Epidemiology and Animal Health, 2150 Centre Ave., Bldg B, Fort Collins, CO 80526-8117 Quality Milk Production Services, College of Veterinary Medicine, Cornell University, Ithaca, NY14850-1263
1 Corresponding author:

Staphylococcus aureus is a major cause of mastitis in dairy cattle. This study estimated the herd prevalence of methicillin-resistant Staph. aureus (MRSA) among US dairy herds by testing bulk tank milk (BTM) samples using genotypic and phenotypic methods. A nationally representative sample of 542 operations had BTM cultured for Staph. aureus, and 218 BTM samples were positive upon initial culture. After 4 wk to 4 mo of frozen storage, 87% of 218 samples (n = 190) were still culture positive for Staph. aureus on blood agar, but none were positive for MRSA on the selective indicator medium CHROMagar MRSA. A duplex PCR was used to detect the Staph. aureus-specific nuc gene and the methicillin resistance gene, mecA, in mixed staphylococcal isolates from the 190 BTM samples that were positive for Staph. aureus after storage. Seven samples tested positive for nuc and mecA, and 2 samples tested positive for mecA only. MecA-positive Staphylococcus spp., but not MRSA, were subsequently isolated from 5 samples, whereas neither mecA-positive Staphylococcus spp. nor MRSA was isolated from the remaining 4 samples. Presence of methicillin-resistant, coagulase-negative Staphylococcus spp. may complicate the detection of MRSA by means of PCR on BTM. Bulk tank milk in the United States is not a common source of MRSA.

Journal of Dairy Science

Thursday, September 17, 2009

Toward the Development of Evidence-Based Guidelines for the Management of Methicillin-Resistant Staphylococcus aureus Otitis.

Toward the Development of Evidence-Based Guidelines for the Management of Methicillin-Resistant Staphylococcus aureus Otitis.

J Otolaryngol Head Neck Surg.
Macneil SD, Westerberg BD, Romney MG.


OBJECTIVES: (1) To determine the causative bacteriology of discharging ears in a case series from a tertiary/quaternary academic centre serving an urban population and from a review of the literature and (2) to develop treatment guidelines for methicillin-resistant Staphylococcus aureus (MRSA) otorrhea based on the best available evidence.

METHODS: A retrospective analysis of all "ear" cultures from the microbiology laboratory at St. Paul's Hospital, Vancouver, was performed to ascertain a qualitative analysis on the susceptibility and bacteriology data. A systematic review of the literature was performed for all studies examining the bacteriology, susceptibility, and treatment for any MRSA infection producing otorrhea.

RESULTS: Staphylococcus aureus and Pseudomonas aeruginosa (PA) were present in 39.7% and 13.5%, respectively, of ear cultures obtained at our institution versus 9.9 to 54.1% and 25.0 to 48.6% in identified studies in the literature. Methicillin-sensitive Staphylococcus aureus (MSSA) was present more frequently than MRSA (31.2% vs 8.5% at our institution; 16.9% vs 6.9% in the literature). MRSA isolates were often resistant to gentamicin (14.8%) and ciprofloxacin (7.7%) but susceptible to trimethoprim-sulfamethoxazole (TMP-SMX) (85.3%) and fusidic acid (96.3%), suggesting a preponderance of the "community strain" of MRSA.

CONCLUSION:The susceptibility of MRSA to antibiotics in commonly used otic drops (ie, gentamicin and ciprofloxacin) is low. Based on the available data, we suggest an evidence-based approach to the management of MRSA otorrhea considering whether the strain is community or hospital acquired and whether the tympanic membrane is intact.


Thursday, June 11, 2009

Methicillin-Resistant Staphylococcus aureus Furunculitis in the Outpatient Burn Setting

Methicillin-Resistant Staphylococcus aureus Furunculitis in the Outpatient Burn Setting

J Burn Care Res. 2009 Jun

Warner P, Neely A, Bailey JK, Yakuboff KP, Kagan RJ.
From the *Shriners Hospitals for Children, Cincinnati, Ohio; and daggerUniversity of Cincinnati, Cincinnati, Ohio.

Methicillin-resistant Staphylococcus aureus (MRSA) is becoming more predominant in the community. We have seen increasing cases of furunculitis in our outpatient burn clinic, which appear to develop weeks after the initial burn injury and in patients with limited inpatient stays. We performed a 3-year retrospective review of all outpatient burn patients who developed furunculitis. Data analyzed included length of hospital stay, type of injury sustained, culture and sensitivity results, and treatment provided. A total of 28 patients were identified with MRSA furunculitis, which presented as painful, hard, indurated boils with minimal purulent drainage. Adults had less extensive burn injuries (mean of 12% TBSA adults vs 20% TBSA children) with shorter hospital stays (mean 8 days adults vs 22 days children). Fifty-seven percent of the patients had multiple furuncules, involving both burned and nonburned areas. Patients with furunculitis had a less resistant MRSA strain than those without furunculitis. Of the 22 patients who received systemic antibiotic coverage, 14 (58%) were successfully treated with 1 antibiotic regimen, whereas 8 (33%) required multiple antibiotics. In this study, furunculitis in the outpatient setting was believed to be consistent with community-acquired MRSA. Incision and drainage was not sufficient in patients with multiple furuncles, and systemic antibiotics were administered. Through increased awareness of the prevalence of community-acquired MRSA in the community, appropriate antibiotic treatment can be initiated, and the discomfort and transmission risk associated with this disease can be minimized.

Lippincott, Williams & Wilkins

Monday, June 8, 2009

Topical Therapy for Methicillin-Resistant Staphylococcus aureus Colonization: Impact on Infection Risk.

Topical Therapy for Methicillin-Resistant Staphylococcus aureus Colonization: Impact on Infection Risk.

Infect Control Hosp Epidemiol. 2009 Jun

Robicsek A, Beaumont JL, Thomson Jr RB, Govindarajan G, Peterson LR.
From the Departments of Medicine (A.R.) and Pathology (R.B.T., L.R.P.), Feinberg School of Medicine, Northwestern University, Chicago, and the Department of Medicine (G.G.), the Division of Infectious Diseases (A.R.), the Division of Microbiology (R.B.T., L.R.P.), and the Center on Outcomes, Research, and Education (J.L.B.), NorthShore University HealthSystem, Evanston, Illinois.


We evaluated the usefulness of topical decolonization therapy for reducing the risk of methicillin-resistant Staphylococcus aureus (MRSA) infection among MRSA-colonized inpatients.


Retrospective cohort study. Setting and intervention. Three hospitals with universal surveillance for MRSA; at their physician's discretion, colonized patients could be treated with a 5-day course of nasal mupirocin calcium 2%, twice daily, plus chlorhexidine gluconate 4% every second day. Patients and methods. MRSA carriers were later retested for colonization (407 subjects; study 1) or followed up for development of MRSA infection (933 subjects; study 2). Multivariable methods were used to determine the impact of decolonization therapy on the risks of sustained colonization (in study 1) and MRSA infection (in study 2).


Independent risk factors for sustained colonization included residence in a long-term care facility (odds ratio [OR], 1.8 [95% confidence interval {CI}, 1.1-3.2]) and a pressure ulcer (OR, 2.3 [95% CI, 1.2-4.4]). Mupirocin at any dose decreased this risk, particularly during the 30-60-day period after therapy; mupirocin resistance increased this risk (OR, 4.1 [95% CI, 1.6-10.7]). Over a median follow-up duration of 269 days, 69 (7.4%) of 933 patients developed infection. Independent risk factors for infection were length of stay (hazard ratio [HR], 1.2 per 5 additional days [95% CI, 1.0-1.4]), chronic lung disease (HR, 1.7 [95% CI, 1.0-2.8]), and receipt of non-MRSA-active systemic antimicrobial agents (HR, 1.8 [95% CI, 1.1-3.1]). Receipt of mupirocin did not affect the risk of infection, although there was a trend toward delayed infection among patients receiving mupirocin (median time to infection, 50 vs 15.5 days; [Formula: see text]).


Mupirocin-based decolonization therapy temporarily reduced the risk of continued colonization but did not decrease the risk of subsequent infection.


Activity of the anti-MRSA carbapenem razupenem (PTZ601) against Enterobacteriaceae with defined resistance mechanisms.

Activity of the anti-MRSA carbapenem razupenem (PTZ601) against Enterobacteriaceae with defined resistance mechanisms.

J Antimicrob Chemother. 2009 Jun

Livermore DM, Mushtaq S, Warner M.
Antibiotic Resistance Monitoring & Reference Laboratory, Health Protection Agency Centre for Infections, 61 Colindale Avenue, London, NW9 5EQ, UK.


Razupenem (previously known as PTZ601, PZ-601, SMP-601 or SM-216601) is a novel carbapenem, active against Enterobacteriaceae as well as Gram-positive bacteria including methicillin-resistant staphylococci and enterococci.


We examined the effect of extended-spectrum beta-lactamases (ESBLs) and AmpC beta-lactamases on the activity of razupenem, using the CLSI agar dilution method to measure MICs for mutants, transconjugants and isolates with and without these enzymes.


ESBLs had no effect on the activity of razupenem against Escherichia coli and Klebsiella spp., and only a small effect when coupled with outer membrane impermeability. Inducible or, more especially, derepressed AmpC enzymes gave some protection, with most AmpC-derepressed Enterobacter and Citrobacter spp. requiring MICs of approximately 8 mg/L. This relative resistance was further increased when porins were lost, restricting drug uptake. Metallo- and class A-carbapenemases conferred resistance, with MICs >/=16 mg/L.


Razupenem has good activity against ESBL producers, but is affected by AmpC enzymes, especially when derepressed and coupled with outer membrane impermeability; its activity is also compromised by carbapenemases.