Staph Infections -- The Latest Bug

[Harrison]

Pharmacokinetic Considerations in the Treatment of Methicillin-resistant Staphylococcus aureus Osteomyelitis

By Meredith B. Toma, PharmD; Kelly M. Smith, PharmD; Craig A. Martin, PharmD; Robert P. Rapp, PharmD
ORTHOPEDICS 2006; 29:497

June 2006

Many treatment options are available for the treatment of methicillin-resistant S aureus osteomyelitis and several factors should be considered when deciding on the best therapy.

In the United States, >2 million Americans become infected with a hospital-acquired organism each year.1 Over 70% of these infections are caused by a bacteria resistant to at least one agent typically used in treatment. Unfortunately, approximately 90,000 of these patients will die. The emergence of multidrug-resistant organisms complicates the treatment of osteomyelitis, an already difficult-to-treat infection.

Staphylococcus aureus is one of the most common bacteria isolated in osteomyelitis cases, and treatment can be difficult because of resistant strains that have emerged.2 Data from 2003 indicate that resistance rates for methicillin-resistant S aureus are approaching 60% in United States intensive care units, a 12% increase from 1998-2002 results.3

table 1Physicians will continue to struggle with methicillin-resistant S aureus osteomyelitis treatment as resistance rates continue to climb. Without proper and prompt treatment of this infection, patients can suffer progressive bone destruction and, ultimately, death. Therefore, it is important to review appropriate treatment options, paying special attention to current standards of care, newer agents, and older agents that may have a novel place in treatment.

The current standard of care for osteomyelitis involves prolonged treatment with antibiotics, usually four to six weeks, in addition to surgical debridement in some instances. Because patients require antibiotic therapy for extended periods of time, it is important to note that a host of factors can alter the effectiveness of antibiotic regimens. These factors include, but are not limited to, type of infection, local resistance patterns, and patient-specific characteristics.4 This article reviews antibiotic treatment options for osteomyelitis caused by methicillin-resistant S aureus including: vancomycin, minocycline, doxycycline, clindamycin, sulfamethoxazole-trimethoprim, linezolid, tigecycline, and daptomycin.

Though some antibiotics are monitored by measuring serum drug concentrations, bone concentrations are of utmost importance when treating methicillin-resistant S aureus osteomyelitis. However, comparison of serum and bone drug concentrations is somewhat problematic. The two parameters are measured in different units with serum concentrations measured in mcg/mL and bone concentrations reported as mcg/g.4 In addition, there is no standardized method for determining bone concentrations of antibiotics. For these reasons, animal models of osteomyelitis often are used to predict bone concentrations of medications. This article discusses pharmacokinetic characteristics, animal models, clinical studies, and observations for each antimicrobial agent.

Vancomycin

Vancomycin demonstrates activity against gram-positive microorganisms, including methicillin-resistant S aureus. It acts by binding to the D-alanyl-D-alanine portion of a cell wall precursor, thus inhibiting cell wall synthesis.5 Vancomycin is available in both oral and intravenous (IV) formulations but only IV vancomycin can be used in the treatment of methicillin-resistant S aureus osteomyelitis. Oral vancomycin is not significantly absorbed from the gastrointestinal tract, and therapeutic serum concentrations needed to treat methicillin-resistant S aureus osteomyelitis are not achieved.

Wilson and Mader6 reported on a rabbit model examining the bone penetration of vancomycin after administration of a single dose (30 mg/kg) in S aureus osteomyelitis. Concentrations were obtained from serum, non-infected, and infected bone (from right and left tibia, respectively). Concentrations in the serum (36.4±4.6 mcg/mL) were higher than in either type of bone. Infected bone samples, however, demonstrated greater penetration of vancomycin than non-infected samples (5.3±0.8 mcg/g versus 3.0±0.2 mcg/g).

A follow-up study in humans examined the concentrations of vancomycin in infected and non-infected bone.7 Non-infected bone samples were obtained from patients who received a vancomycin dose of 15 mg/kg prior to total hip replacement. Infected bone samples were collected from patients with sternal or tibial osteomyelitis receiving vancomycin doses based on serum concentrations (peaks 20-40 mcg/mL; troughs=12 mcg/mL). Again, patients with infected bone showed higher concentrations of vancomycin. Concentrations in both cancellous and cortical bone were higher in patients with infected bone, when compared to patients with uninfected bone (3.6 mcg/g versus 2.3±4.0 mcg/g and 5.94±3.48 mcg/g versus 1.14±0.84 mcg/g, respectively).

It is important to note that higher vancomycin trough concentrations of 15-20 mcg/mL are the current standard of practice when treating osteomyelitis, as opposed to the trough levels <12 mcg/mL used in Graziani et al’s7 study. Thus, one would expect to see higher concentrations in infected bone compared to study results. Some proposed mechanisms for increased infected bone concentrations include: better blood flow, serum trapping of the medication, or increased penetration of the chosen antibiotic.6 Regardless of the mechanism, vancomycin concentrations in bone range from 15%-35% of those seen in the serum, well above the minimum inhibitory concentration of 1 mcg/ml for susceptible S aureus strains.7 Today, vancomycin is commonly used for methicillin-resistant S aureus osteomyelitis and practitioners are comfortable with this agent. Vancomycin serum concentrations can be obtained to ensure that patients are receiving adequate treatment doses without adverse effects.
Tetracyclines

Tetracycline antibiotics, specifically minocycline and doxycycline, are active against methicillin-resistant S aureus in a bacteriostatic fashion. These agents enter bacterial cells in two ways, either by passive diffusion or an energy-dependent transport system.5,8 Once inside the cell, tetracyclines inhibit cell wall synthesis by binding to the 30S ribosomal unit that halts protein synthesis. Both agents are lipophilic, facilitating their passage into tissues.9

In a case series of 24 patients with methicillin-resistant S aureus infections treated with minocycline or doxycycline, clinical success occurred in 83% of patients.10 This study included four patients with osteomyelitis who were treated with minocycline alone (n=1), minocycline plus rifampin (n=2), or minocycline plus sulfamethoxazole-trimethoprim (n=1). The cure rate of 50% in patients with osteomyelitis was lower than that seen in the entire study population. The reasons for treatment failure were not specified, but the authors postulate it may be attributed to development of resistance to rifampin by the methicillin-resistant S aureus isolate. The overall resistance of methicillin-resistant S aureus to tetracycline antibiotics is approximately 16% in the United States (Table 1).11 This may indicate that doxycycline and minocycline may be suitable for outpatient therapy of methicillin-resistant S aureus osteomyelitis. Perhaps these two agents can be used in patients who have finished four to six weeks of IV antibiotics, but continued suppressive oral antibiotic therapy is necessary.

table 2
Clindamycin

Clindamycin is another older antimicrobial agent that may have a newfound place in the treatment of methicillin-resistant S aureus osteomyelitis. The lincosamide antibiotic exerts its effect on bacteria by acting on the ribosome to prevent protein synthesis, but interacts at different locations compared to previously mentioned antimicrobials (Table 2).12 It is theorized that the efficacy of clindamycin in gram-positive osteomyelitis can be attributed to its bone penetration, despite its classification as a bacteriostatic agent.13

A rabbit model of osteomyelitis demonstrated that clindamycin achieves significant concentration in bone.14 Rabbits were infected with S aureus osteomyelitis and divided into three treatment groups: no antibiotic therapy, 30 mg/kg clindamycin 3 times per day for 28 days, or 30 mg/kg clindamycin 3 times daily for 14 days. Serum and bone concentrations were examined one, two, and four hours after injection. Serum levels were found to be 11.7±3.2 mcg/mL, 6.6±0.8 mcg/mL, and 2.1±0.1 mcg/mL, respectively. Bone concentrations indicate that clindamycin achieved concentrations 29, 28, and 10 times greater than the organism minimum inhibitory concentration (MIC) (4.6±1.1 mcg/g, 4.3±0.7 mcg/g, and 1.6±0.3 mcg/g, respectively). These concentrations resulted in bone sterilization rates of 84%, with a greater percentage of rabbits treated for 28 days showing negative cultures at the end of treatment compared to those treated for only 14 days (84% versus 22%). Caution should be used when interpreting the above study results. Concentrations achieved in bone depend on the serum concentration obtained and differs between patients. Thus, bone concentrations achieved may not mimic those seen by Norden et al.14

A case series of 29 pediatric patients confirmed the efficacy of clindamycin in both acute and chronic cases of osteomyelitis.15 Patients initially received clindamycin 100 mg/kg/day IV for four weeks and then clindamycin 30 mg/kg/day orally for four additional weeks. Doses later were decreased to 50 mg/kg/day IV for three weeks and 25 mg/kg/day orally for four to six weeks because serum concentrations easily exceeded the susceptibility breakpoint for S aureus. Maximal serum concentrations were 32 mcg/mL one hour after clindamycin infusion. Bone concentrations determined six hours after administration of a 25 mg/kg dose were 42%-46% of those achieved in the serum, far above the breakpoints. A smaller clindamycin dose of 12.5 mg/kg showed a bone concentration equal to 30% of the serum concentration.

Clindamycin bone penetration also has been examined in adults undergoing knee or hip replacement.16 Clindamycin 600 mg IV every 8 hours was initiated between 12 and 20 hours prior to incision. During the procedure, cancellous bone was removed from the femoral neck or head. Two of three patients treated with clindamycin showed measurable concentrations in bone (9.26 mcg/g and 7.33 mcg/g). Concurrent serum concentrations were 12.5 mcg/mL and 10.0 mcg/mL, respectively.

Evidence from the literature has suggested two situations appropriate for the use of clindamycin in methicillin-resistant S aureus osteomyelitis. First, extended courses of oral clindamycin may be used in patients who display osteomyelitis refractory to other agents.17 Second, community-acquired methicillin-resistant S aureus infections often retain susceptibility to clindamycin.18

Sulfamethoxazole-Trimethoprim

The use of sulfamethoxazole-trimethoprim (SMX-TMP), a combination agent with observed activity against methicillin-resistant S aureus, has been well documented in both hospital-acquired and community-acquired infections, and overall resistance rates of methicillin-resistant S aureus appear to be low (26%) (Table 2). A case series of six patients with methicillin-resistant S aureus osteomyelitis demonstrated its efficacy.19 Five of these patients previously had received antibiotics, including vancomycin, for osteomyelitis without resolution. Sulfamethoxazole-trimethoprim was initiated at a dose of 800 mg/160 mg (one double strength tablet) every six hours; osteomyelitis resolved in five of the six patients. Four patients received sulfamethoxazole-trimethoprim for 8-12 weeks, one patient responded but had neutropenia successfully treated with folinic acid, and one patient remained on therapy for at least 56 weeks.

Perhaps the greatest role of sulfamethoxazole-trimethoprim lies in the continuation of antibiotic therapy after initial IV antibiotics have been used. Often sulfamethoxazole-trimethoprim will be given in combination with rifampin in the outpatient setting.20 Also, the use of sulfamethoxazole-trimethoprim has been suggested in the suppression of osteomyelitis. As with clindamycin, sulfamethoxazole-trimethoprim is an acceptable option for use in community-acquired methicillin-resistant S aureus infections.21
Newer Antimicrobials

Linezolid, a synthetic oxazolidinone, has emerged as a new treatment for methicillin-resistant S aureus infections. It most often is used in patients intolerant of vancomycin therapy or those experiencing treatment failure while receiving vancomycin.22 It is available in both IV and oral formulations and requires no dosage adjustment in liver or renal failure (caution should be used in severe hepatic failure).

A compassionate use program in human subjects conducted between 1997 and 2000 showed clinical success in 90% of linezolid treated patients with osteomyelitis (caused by methicillin-resistant S aureus or vancomycin-resistant enterococci), with an average duration of therapy of 40 days.23 In this same study, treatment success for methicillin-resistant S aureus infections was 86.6%. Perhaps the greatest benefit of linezolid is the available oral formulation with almost 100% bioavailability.5 However, linezolid therapy comes with a significant financial burden to patients. In addition, linezolid causes reversible myelosuppression, and patients undergoing prolonged treatment should have complete blood cell counts monitored regularly.24 For these reasons, other treatment options should be considered in patients when frequent monitoring is not possible.

Another new option in the fight against methicillin-resistant S aureus infection is tigecycline, a glycylcycline antibiotic structurally related to minocycline that exhibits bacteriostatic action. This agent has a large volume of distribution, suggestive of rapid distribution into tissues.25,26 Radio-labeled tigecycline given to rats showed greatest concentrations in the liver, spleen, and bone at the end of a 30-minute infusion. Levels were estimated to be eight times higher than in serum, and the half-life in bone was predicted to be approximately 200 hours.27 One benefit that tigecycline may have over its precursors is protection from established mechanisms of resistance common to the tetracycline class.9 Though tetracyclines and glycylcyclines bind to the same location of the bacterial ribosome, tigecycline has a stronger binding affinity. This may offer protection against the ribosomal resistance mechanism that can either prevent binding of the drug at the ribosome or promote dissociation from the site of action.

Daptomycin is a bactericidal cyclic lipopeptide that binds to bacterial cell membranes and causes depolarization.28This, in turn, alters protein synthesis in the bacteria. Daptomycin was compared to vancomycin in a rabbit model of methicillin-resistant S aureus osteomyelitis.29 Rabbits were given either daptomycin 4 mg/kg IV every 12 hours or vancomycin 40 mg/kg IV every 6 hours. Concentrations of both agents were significantly higher in infected bone when compared to non-infected bone. Methicillin-resistant S aureus eradication rates in this study were 41% for rabbits receiving daptomycin and 39% for vancomycin-treated rabbits. Mader and Adams29 noted the similar efficacy between the two agents and also noted that higher treatment success rates should be expected with either agent in humans, as humans with methicillin-resistant S aureus osteomyelitis will likely undergo debridement in addition to antibiotic therapy. Although daptomycin treatment of methicillin-resistant S aureus sounds promising, there have been recent reports of methicillin-resistant S aureus strains with reduced or no susceptibility to daptomycin.30-32 Therefore, clinicians should use this agent cautiously.

Conclusion

There are many treatment options available for the treatment of methicillin-resistant S aureus osteomyelitis and several factors should be considered when deciding on the best therapy. These include the type of osteomyelitis (acute versus chronic), previous antibiotic therapy, duration of therapy, and cost. Many of the above agents can be used once a patient has completed initial therapy with IV antibiotics but continued antimicrobials are desired. The use of oral agents in the long-term may help to enhance patient adherence and have potential benefits in eradication of the infecting organism. Previously, physicians may have felt limited to the use of vancomycin for methicillin-resistant S aureus osteomyelitis. This article identifies emerging antimicrobial agents for methicillin-resistant S aureus osteomyelitis and illustrates that older medications still have a place in therapy, allowing clinicians to expand treatment options outside of vancomycin.

The Bottom Line

* Finding the best treatment options for methicillin-resistant S aureus osteomyelitis continues to be difficult.
* Several established antibiotic options demonstrate good bone penetration.
* Other antibiotics, with limited clinical data in methicillin-resistant S aureus osteomyelitis, have demonstrated clinical success.
* Newer agents show promise in treatment of methicillin-resistant S aureus infections and may lack issues associated with resistance of classical agents.

References

1. Centers for Disease Control and Prevention. Antimicrobial Resistance in Healthcare Settings. Accessed February 22, 2006. Available at: http://www.cdc.gov/ncidod/dhqp/ar.html.
2. Lew DP, Waldvogel FA. Osteomyelitis. N Eng J Med. 1997; 336:999-1007.
3. National Nosocomial Infections Surveillance (NNIS) System Report, data summary from January 1992 through June 2004, issued October 2004. Am J Infect Control. 2004; 32:470-485.
4. Mader JT, Shirtliff ME, Bergquist SC, Calhoun J. Antimicrobial treatment of chronic osteomyelitis. Clin Orthop. 1999; 360:47-65.
5. Micromedex. Micromedex Healthcare Series. Accessed February 10, 2006. Available at: http://www.uky.edu/Libraries/record.php?lir_id=764.
6. Wilson KJ, Mader JT. Concentrations of vancomycin in bone and serum of normal rabbits and those with osteomyelitis. Antimicrob Agents Chemother. 1984; 25:140-141.
7. Graziani AL, Lawson LA, Gibson GA, Steinberg MA, MacGregor RR. Vancomycin concentrations in infected and noninfected human bone. Antimicrob Agents Chemother. 1988; 32:1320-1322.
8. Minocycline: Drug information. Accessed: March 17, 2006. Available at: http://www.utdol.com/utd/content/topic.do?topicKey=drug...A&selectedTitle=1~35.
9. Zhanel GG, Homenuik K, Nichol K, et al. The glycylcyclines: a comparative review with the tetracyclines. Drugs. 2004; 64:63-88.
10. Ruhe JJ, Monson T, Bradsher RW, Menon A. Use of long-acting tetracyclines for methicillin-resistant Staphylococcus aureus infections: case series and review of the literature.Clin Infect Dis. 2005; 40:1429-1434.
11. Diekema DJ, Pfaller PM, Schmitz FJ, et al. Survey of infections due to Staphylococcus species: frequency of occurrence and antimicrobial susceptibility of isolates collected in the United States, Canada, Latin America, Europe, and the Western Pacific region for the SENTRY Antimicrobial Surveillance Program, 1997-1999. Clin Infect Dis. 2001; 32(suppl 2):S114-S132.
12. Clindamycin: Drug information. Accessed March 17, 2006. Available at: http://www.utdol.com/utd/content/topic.do?topicKey=drug...A&selectedTitle=2~82.
13. Pankey GA, Sabath LD. Clinical relevance of bacteriostatic versus bactericidal mechanisms of action in the treatment of gram-positive bacterial infections. Clin Infect Dis. 2004; 38:864-870.
14. Norden CW, Shinners E, Niederriter K. Clindamycin treatment of experimental chronic osteomyelitis due to Staphylococcus aureus.J Infect Dis. 1986; 153:956-959.
15. Rodriguez W, Ross S, Khan W, McKay D, Moskowitz P. Clindamycin in the treatment of osteomyelitis in children: a report of 29 cases. Am J Dis Child. 1977; 131:1088-1093.
16. Smilack JD, Flittie WH, Williams TW Jr. Bone concentrations of antimicrobial agents after parenteral administration. Antimicrob Agents Chemother. 1976; 9:169-171.
17. Haas DW, McAndrew MP. Bacterial osteomyelitis in adults: Evolving considerations in diagnosis and treatment. Am J Med. 1996; 101:550-561.
18. Martinez-Aguilar G, Hammerman WA, Mason EO Jr, Kaplan SL. Clindamycin treatment of invasive infections caused by community-acquired, methicillin-resistant and methicillin-susceptible Staphylococcus aureus in children. Pediatr Infect Dis J. 2003; 22:593-598.
19. Yeldandi V, Strodtman R, Lentino JR. In-vitro and in-vivo studies of trimethoprim-sulfamethoxazole against multiple resistant Staphylococcus aureus. J Antimicrob Chemother. 1988; 22:873-880.
20. Stein A, Bataille JF, Drancourt M, et al. Ambulatory treatment of multidrug-resistant Staphylococcus-infected orthopedic implants with high-dose oral co-trimoxazole (trimethoprim-sulfamethoxazole). Antimicrob Agents Chemother. 1998; 42:3086-3091.
21. Treatment of community-acquired MRSA infections. Med Lett Drugs Ther. 2006; 48:13-14.
22. Rayner CR, Baddour LM, Birmingham MC, Norden C, Meagher AK, Schentag JJ. Linezolid in the treatment of osteomyelitis: results of compassionate use experience. Infection. 2004; 32:8-14.
23. Broder KW, Moise PA, Schultz RO, Forrest A, Schentag JJ. Clinical experience with linezolid in conjunction with wound coverage techniques for skin and soft-tissue infections and postoperative osteomyelitis. Ann Plast Surg. 2004; 52:85-90.
24. Gerson SL, Kaplan SL, Bruss JB, et al. Hematologic effects of linezolid: summary of clinical experience. Antimicrob Agents Chemother. 2002; 46:2723-2726.
25. Livermore DM. Tigecycline: what is it, and where should it be used? J Antimicrob Chemother. 2005; 56:611-614.
26. Meagher AK, Ambrose PG, Grasela TH, Ellis-Grosse EJ. Pharmacokinetic/pharmacodynamic profile for tigecycline-a new glycylcycline antimicrobial agent. Diagn Microbiol Infect Dis. 2005; 52:165-171.
27. Tombs N. Tissue distribution of GAR-936, a broad-spectrum antibiotic, in male rats. Presented at the 39th ICAAC Program and Abstracts. September 26-29, 1999, San Francisco, Calif.
28. Daptomycin: Drug information. Accessed March 30, 2006. Available at: http://www.utdol.com/utd/content/topic.do?topicKey=drug...A&selectedTitle=1~11.
29. Mader JT, Adams K. Comparative evaluation of daptomycin (LY146032) and vancomycin in the treatment of experimental methicillin-resistant Staphylococcus aureus osteomyelitis in rabbits. Antimicrob Agents Chemother. 1989; 33:689-692.
30. Hayden MK, Rezai K, Hayes RA, Lolans K, Quinn JP, Weinstein RA. Development of daptomycin resistance in vivo in methicillin-resistant Staphylococcus aureus.J Clin Microbiol. 2005; 43:5285-5287.
31. Marty FM, Yeh WW, Wennersten CB, et al. Emergence of a clinical daptomycin-resistant Staphylococcus aureus isolate during treatment of methicillin-resistant Staphylococcus aureus bacteremia and osteomyelitis. J Clin Microbiol. 2006; 44:595-597.
32. Vikram HR, Havill NL, Koeth LM, Boyce JM. Clinical progression of methicillin-resistant Staphylococcus aureus vertebral osteomyelitis associated with reduced susceptibility to daptomycin. J Clin Microbiol. 2005; 43:5384-5387.

Authors

Drs Toma, Smith, Martin, and Rapp are from the University of Kentucky Chandler Medical Center, Lexington, Ky.

Reprint requests: Kelly M. Smith, PharmD, 800 Rose St, Rm C-113, Lexington, KY 40536.

Courtesy OthoSupersite

[Eddie_G]

My grandmother is currently hospitalized with this.
Are some of the symptoms slurred speech and quasi-drunkenness?

She is not being medicated with anything that would cause this...

[tmont]

This is a subject--and a health problem--that is really taking off--I was asked to translate a paper on a study of these infections for publication in US and British medical journals, ASAP....

Heads up and watch where you step and what you put in your mouth!

[Harrison]

Drug-Resistant Staph Bacteria Seem to Be Widespread in U.S.
By ROBERT TOMSHO
August 17, 2006; Page D4

Drug-resistant staph bacteria are present in 59% of skin and soft-tissue infections treated in emergency rooms, according to a new study that suggests physicians revamp treatment strategies.

The study, which looked at patients treated at emergency rooms in New York, Los Angeles and nine other cities, adds to a growing body of research pointing to the increased prevalence of the bacteria known as MRSA, or methicillin-resistant staphylococcus aureus. Methicillin is a penicillin-related drug once used to treat such staph infections.

The study, published in the New England Journal of Medicine, also found many of the infected patients had USA300, a virulent new form of MRSA often transmitted from person to person in communities, outside hospitals.

In recent years, community-associated MRSA has broken out among prisoners, intravenous-drug users, military trainees and athletes. Untreated, it can lead to pneumonia and more serious infections of the blood and bones.

The study suggests physicians should presume MRSA is present when they treat such infections and prescribe drugs thought to be effective against it. "The take-home message for physicians would be to recognize just how common this is now," said Gregory Moran, the study's lead author and an emergency-room physician at the Olive View-UCLA Medical Center, in Sylmar, Calif.

An editorial in the New England Journal said the study "defines the amazing extent to which community-associated MRSA, particularly the USA300 clone, has spread through the U.S. population."

C. Buddy Creech, a professor of pediatric infectious diseases at Vanderbilt University Medical School, said the study validates what many physicians have been seeing for several years. "Now we have good reproducible data that can drive our treatment options," said Dr. Creech, who didn't take part in the study.

The study looked at 422 emergency-room patients in August 2004. MRSA was found in 249 of those patients. The USA300 strain was detected in 212 of the 218 patient tissue samples that were sent to the U.S. Centers for Disease Control and Prevention for further testing.

The study suggests physicians take tissue samples from all patients for testing and treat them with an antibiotic such as trimethoprim-sulfa.

Courtesy of Wall St. Journal, August 17, 2006.

[Alastair]

The sad thing about the MRSA bug, is that it could be almost eradicated completely if people would simply wash their hands -- -- -- especially in hospitals.

The UK is now working on the basis of nurses wash their hands between patients -- -- -- that should be standard practice in every hospital. It just shows how much we have let standards slip
Best,
Alastair

[Harrison]

Monday, November 6, 2006

MRSA Toxin Acquitted: Study Clears Suspected Key to Severe Bacterial Illness

Researchers who thought they had identified the bacterial perpetrator of the often severe disease caused by community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) had better keep looking: Scientists at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, have exonerated a toxin widely thought to be the guilty party.

Panton-Valentine leukocidin (PVL) is one of many toxins associated with S. aureus infection. Because it can be found in virtually all CA-MRSA strains that cause soft-tissue infections, several research groups previously have proposed that PVL is the key virulence factor.

But new evidence strongly suggests that is not the case. A study led by NIAID researchers at Rocky Mountain Laboratories (RML) in Hamilton, MT, shows that the two major epidemic CA-MRSA strains and the same strains with PVL removed are equally effective at destroying human white blood cells — our primary defense against bacterial infections — and spreading disease. The findings, which appear online in The Journal of Infectious Diseases, are surprising because many scientists had presumed that CA-MRSA uses PVL to target and kill specific white blood cells known as neutrophils.

“The Staphylococcus aureus bacterium is a growing global public health menace because of its rapid spread from hospital settings into communities of healthy people,” says NIAID Director Anthony S. Fauci, M.D. “This is an evolving pathogen that in recent decades has developed resistance to common medical treatments and now is finding new mechanisms to spread and cause severe illness.”

About 75 percent of CA-MRSA infections are localized to skin and soft tissue and usually can be treated effectively. CA-MRSA strains have enhanced virulence, meaning they can infect otherwise healthy people. One of the biggest problems with CA-MRSA skin infections is that they spread rapidly and have the potential to cause illness much more severe than traditional hospital-associated MRSA infections, where PVL is less common. These life-threatening infections can affect vital organs and lead to widespread infection (sepsis), toxic shock syndrome and flesh-eating pneumonia. It is not known why some healthy people develop CA-MRSA skin infections that are treatable whereas others infected with the same strain develop severe infections or die.

Scientists had recognized a connection between MRSA strains that contain PVL and the increased occurrence and severity of CA-MRSA disease, though no one had directly tested the role of PVL in CA-MRSA virulence. In striving to learn more about CA-MRSA, the RML scientists, with their colleagues at the International Center for Public Health (ICPH) in Newark, NJ, and the Université Claude Bernard in Lyon, France, decided to test the PVL virulence theory, thinking that if they could understand the role of this toxin in disease, they could more quickly diagnose serious cases and develop effective treatments.

In addition to observing the destruction of human white blood cells regardless of whether PVL was present, the researchers also used mouse models to learn that CA-MRSA strains are just as pathogenic with or without PVL present. These findings were seen in tests with mice that displayed skin and soft-tissue infection and bacterial sepsis.

“The strains were just as deadly with or without the PVL toxin,” says lead investigator Frank DeLeo, Ph.D., of RML. “Unexpectedly, the average abscess volume in mice infected with strains absent the PVL was slightly greater than those containing the toxin. The strong association between PVL and CA-MRSA makes the toxin an excellent marker to track community strains, but the assumption that it is the major virulence determinant driving this epidemic is simply not true.”

These findings are significant because some infectious disease physicians who treat MRSA patients had begun questioning whether PVL truly led to severe illness, says Barry Kreiswirth, Ph.D., study co-author and a leading staphylococcal epidemiologist from ICPH in Newark. He adds, “We routinely receive calls from clinical microbiology laboratories asking to test for the presence of PVL, and it is hard to dissuade them that the PVL results will not affect patient care. Hopefully, the robust and contrary findings in our study provide the experimental evidence to convince the staphylococcal researchers and clinicians that PVL is not a significant virulence factor.”

Next, Dr. DeLeo says his group will shift away from PVL and try to determine exactly which toxin or other mechanism in S. aureus kills white blood cells and allows the spread of CA-MRSA infection.

NIAID is a component of the National Institutes of Health. NIAID supports basic and applied research to prevent, diagnose and treat infectious diseases such as HIV/AIDS and other sexually transmitted infections, influenza, tuberculosis, malaria and illness from potential agents of bioterrorism. NIAID also supports research on basic immunology, transplantation and immune-related disorders, including autoimmune diseases, asthma and allergies. News releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at http://www.niaid.nih.gov.

The National Institutes of Health (NIH) — The Nation's Medical Research Agency — includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.
Reference: J Voyich et al. Is Panton-Valentine leukocidin the major virulence determinant in community-associated methicillin-resistant Staphylococcus aureus disease? The Journal of Infectious Diseases 194(12), (2006).

[Alastair]

Questions About MRSA and Answers From the Experts from medscape today
Posted 11/01/2006

Laura Stokowski, RN, MS

The Uncertainties Surrounding Multidrug-Resistant Organisms
Over the past several months, we have received dozens of questions about multidrug-resistant organisms (MDROs). In particular, readers have asked about methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) through our Ask the Expert feature on Medscape Nurses. Clearly, nurses and other clinicians are concerned about MDROs, and are seeking answers to many practical, clinical questions ranging from the best way to identify patients with MRSA to what healthcare professionals should do if they have personally had an MRSA infection.

The fact that there is no single set of guidelines that all hospitals are required to follow no doubt adds to the confusion. One hospital handles MRSA patients one way, whereas another hospital handles them a different way; both are correct -- a situation that is perplexing to many healthcare professionals.

We took your questions to the following experts: John Jernigan, MD, MS, and Rachel Gorwitz, MD, MPh, Medical Epidemiologists with the US Centers for Disease Control and Prevention (CDC); Elizabeth Bancroft, MD, SM, Medical Epidemiologist with the Los Angeles County Department of Health Services; and Shannon Oriola, RN, CIC, COHN, Chair, Association for Professionals in Infection Control and Epidemiology (APIC) Public Policy Committee.

How are MDROs -- MRSA and VRE -- defined? The term MRSA refers to those strains of S aureus bacteria that have acquired resistance to the antibiotics methicillin, oxacillin, nafcillin, cephalosporins, imipenem, and/or other beta-lactam antibiotics. Enterococci are gram-positive bacteria that are found normally in the gastrointestinal and female genital tracts. All enterococci have intrinsic low-level resistance to some antibiotics. In recent years, however, some strains of enterococci have acquired high-level resistance to multiple antibiotics, including aminoglycosides, ampicillin, and vancomycin. Infection caused by VRE is of special concern, however, because it is very difficult to treat.

What is the difference between colonization and infection with bacteria, such as MRSA and VRE? Colonization refers to the presence of microorganisms in or on a host with growth and multiplication, but without tissue invasion or damage. In the case of MRSA, the body site most commonly colonized is the anterior nares.[1] Other body sites that may be colonized with MRSA include open wounds, the respiratory tract, perineum, upper extremities, umbilicus (in infants), urinary tract, and axilla. VRE colonization is generally in the stool. MRSA or VRE colonization can serve as a reservoir for the spread of these microorganisms to others, and can lead to infection in the host. Colonized patients are also known as asymptomatic carriers.

Infection is the entry and multiplication of microorganisms in the tissues of the host leading to local or systemic signs and symptoms of infection.

MRSA and VRE can cause invasive and life-threatening infections, such as osteomyelitis, bacteremia, endocarditis, pneumonia, urinary tract infections, intra-abdominal or pelvic infections, vascular line sepsis, and wound and surgical infections.

What is community-acquired MRSA? How is it different from healthcare-acquired MRSA? In epidemiologic investigations, MRSA infections in persons who have not been recently (within the past year) hospitalized or had a medical procedure (such as dialysis, surgery, or catheters) are classified as community-associated MRSA (CA-MRSA) infections. The strains of MRSA that most commonly cause CA-MRSA infections are distinct from those that were already established in healthcare settings. These new strains have now also entered and are being transmitted in some healthcare facilities. However, Rachel Gorwitz, MD, MPh, Medical Epidemiologist with the CDC, emphasizes that clinical management of MRSA infections does not depend on categorization of the infection as healthcare-associated vs community-associated or on strain typing. Treatment of an infection possibly caused by MRSA should be based on the clinical syndrome, severity of the infection, and local resistance patterns. Similarly, infection control practices should be uniform for all patients colonized or infected with MRSA.

Most MRSA infections in otherwise healthy individuals in the community present as skin or soft-tissue infections, such as a boils or abscesses. MRSA skin lesions are frequently confused with spider bites by both patients and healthcare providers. The lesion is red, swollen, and painful and may have pus or other drainage (Figures 1 and 2). Less commonly, CA-MRSA infections present as more serious or invasive infections, such as bloodstream infections, pneumonia, or osteomyelitis. (Readers may also wish to review these photographs of MRSA infections from the County of Los Angeles, California, Department of Health Services.)


Figure 1. (click image to zoom)
Cutaneous abscess located on the hip of a prison inmate, which had begun to spontaneously drain, releasing its purulent contents. The abscess was caused by MRSA bacteria.




Figure 2. (click image to zoom)
Cutaneous abscess on the knee, caused by MRSA.



I am confused by the need to isolate a patient who was diagnosed with MRSA in a wound years ago. The hospitals where I have worked state "once an MRSA patient, always an MRSA patient." The wound is healed and gone and there are no signs of active infection. Do we really need to isolate these patients? Individuals who become colonized with MRSA tend to remain colonized for months or even years.[1] It is important to realize that individuals colonized with MRSA can serve as reservoirs for MRSA and transmit the bacteria to others, just as those infected with MRSA. This is why many hospitals choose to assume that patients who were formerly colonized with MRSA are likely to still be colonized with MRSA. Their medical records are flagged so that contact precautions can immediately be resumed if these patients return to the hospital. Another option would be to obtain nasal cultures or series of cultures to determine whether former MRSA patients are indeed still colonized.

Our hospital policy is to isolate every patient who is admitted to our hospital unit. Everyone is treated as if they are colonized with MRSA until proven otherwise. Once we obtain a negative culture (usually within 24 hours), we take them out of isolation. Please comment on this policy. Screening all or a high- risk subset of patients for MRSA upon admission to the facility or nursing unit is known as "active surveillance." It is a strategy used to control the transmission of pathogens, such as MRSA, that is widely practiced in northern Europe and Canada and is becoming more common in hospitals throughout the United States. Active surveillance cultures are recommended by the Society for Healthcare Epidemiology of America (SHEA).[2] In a study recently conducted at Brigham and Women's Hospital in Boston, Massachusetts, routine MRSA admission cultures and contact isolation precautions resulted in a 67% hospital-wide reduction in MRSA bacteremia.[3]

The aim of active surveillance cultures is to identify every patient who is colonized with MRSA and to use contact precautions to prevent the spread of MRSA to other patients or to healthcare workers. In some hospitals, high-risk patients are assumed to be carriers of MRSA, and contact precautions are used until a negative culture is obtained.

MRSA and VRE infections increase the duration of hospitalizations, increase mortality, and increase costs.[2] The use of active surveillance cultures and contact isolation is one of several important strategies available for preventing the transmission of MRSA. Active surveillance of all admissions, as described above, can be streamlined further with the use of rapid diagnostic technology, such as polymerase chain reaction, which can provide a result in 2 hours once the specimen is set up to be processed in the laboratory.

What is the correct protocol for taking patients off of MRSA precautions? If a formerly MRSA-positive patient becomes negative after 3 consecutive negative cultures, do you still consider this patient to be an MRSA carrier, or do you consider him/her to be free of MRSA and take him/her out of contact precautions? There is no single, correct protocol for taking patients off of contact precautions. If patients have been colonized in the recent past, healthcare facilities should make an attempt to prove that they are no longer colonized before taking them out of isolation. There are no data in regard to how many cultures should be taken for this purpose, or for the interval between cultures. At this time, healthcare facilities should establish their own protocols detailing both the number of cultures required and the length of time between cultures, but according to some experts, it seems reasonable to discontinue contact precautions when 3 or more surveillance cultures are repeatedly negative over the course of a week.

How should patients with MRSA be handled in the emergency department? Should they be isolated? Is isolation with a curtain sufficient? Can these patients use a shared bathroom? MRSA is being seen with increasing frequency in emergency departments (EDs). It is the most common identifiable cause of purulent skin and soft-tissue infections among patients presenting to EDs.[4] Contact precautions for MRSA patients were designed for private room settings, a luxury that is not always available in the ED. When it isn't possible to place the patient in a separate room, the principles of contact precautions can still be applied in areas that are separated only by curtains. Remember that the primary route of transmission of MRSA from patient to patient is via the transiently contaminated hands of healthcare workers. Although it may not be an option in most EDs to provide a separate bathroom for MRSA patients, it makes the most sense in this environment to focus on the things that you can do to prevent transmission of MRSA, such as hand hygiene, wearing gloves and gowns for contact, and proper disinfection of the area after the patient is discharged. Patients should also be educated about how to prevent further transmission of the infection, eg, keeping wounds or lesions covered with clean, dry bandages; practicing good hand hygiene; and avoiding the sharing of contaminated items.[4]

To transport an MRSA patient, we have been told to place a clean gown over the patient and place a mask on the patient. Is this the best approach? Shannon Oriola, RN, CIC, COHN, recommends that, when transporting an MRSA patient, a chief concern is avoiding actions that require the nurse or other attendant to touch the patient and then possibly contaminate environmental surfaces (door handles, elevator buttons, etc). If a single caregiver is transporting the patient, gown and gloves are worn until the patient is on the stretcher or wheelchair, and then gloves are removed and hands are washed. This caregiver then transports the patient without having any direct patient contact.

If it is anticipated that the patient might require some hands-on intervention during the transport; the safest approach is to have 2 individuals transport the patient. One wears gown and gloves and is responsible for touching the patient, if needed, during the transport. The other individual, without gloves, handles the doors and elevator buttons.

A mask is required only if the patient is on droplet precautions as recommended by the CDC.

I work in the operating room as a nurse anesthetist. Is it necessary to change the soda lime after every MRSA/VRE or HIV patient? We currently do change it, but is it really necessary? Soda lime is used in breathing systems to absorb exhaled CO2 during anesthesia. A mixture of calcium oxide and sodium or potassium hydroxide, soda lime, was once thought to be bactericidal. It is now known that soda lime is toxic to some microorganisms,[5] but only if combined with CO2 to form a saturated solution with a pH > 12.[6] Even then, some organisms can survive for extended periods of time within the canister because they are deposited on desiccated surfaces, which are nontoxic.[6]

Even if viable bacteria, such as S aureus, do pass unimpeded through the anesthetic circuit, the potential for transmission to other patients depends on many other factors,[6] including the number of pathogens, their virulence, and their distribution; how frequently the anesthesia circuit is used and the time between cases; and the immune competence of patients. These variables all contribute to the overall risk of acquiring a respiratory cross-infection following anesthesia.[6]

In their 2003 report, Guidelines for the Prevention of Healthcare-Associated Pneumonia, the CDC considered this issue but was unable to make a recommendation. Here is the wording from the report: "No recommendation can be made about the frequency of routinely cleaning and disinfecting unidirectional valves and carbon dioxide absorber chambers (Unresolved issue).[7]"

What is the best way to manage a patient with MRSA on a behavioral health unit? Most behavioral health units are low-risk settings for the transmission of MRSA and for infection with MRSA. Patients usually take part in group and activity therapies that make isolation impractical. For this reason, most behavioral health units are treated like community settings, and are considered exempt from hospital isolation guidelines. The exception would be if a patient has an actively draining wound infected or colonized with MRSA. Wounds, if present, should be covered with clean, dry dressings. Gloves and gowns are worn by caregivers if wound contact is necessary.

The best way to prevent the transmission of MRSA on the behavioral health unit is to educate patients and staff members to practice good hand hygiene. Patients should not share potentially contaminated personal items, such as towels, soap, or razors.

If a patient is treated for MRSA or VRE with intravenous antibiotics, is he/she no longer colonized? Treating for MRSA or VRE infection with intravenous antibiotics, even with successful resolution of the infection, does not always mean that colonization is eradicated, emphasized John Jernigan, MD, MS, of the CDC. Signs and symptoms of clinical infection may be gone (fever, swelling, erythema, and purulent drainage) and the white blood cell count may return to normal following antibiotic treatment. However, colonization with MRSA or VRE can persist, and the patient can continue to be a carrier.

Please help our staff determine the correct way to clean in a room after a patient with MDRO has occupied it. We are not sure about how to clean the drapes, walls, and surfaces. Careful cleaning of patient rooms and medical equipment is important to overall control of transmission of MDRO and other pathogens in healthcare facilities. Follow routine cleaning procedures for floors and walls. Surfaces that are visibly soiled should be washed first before disinfecting. Frequently touched surfaces (eg, bed rails, overbed tables, doorknobs, equipment in the immediate vicinity of the patient, bathroom fixtures in the patient's room, etc) deserve special focus and should be cleaned on a more frequent schedule compared with that for minimal touch surfaces (eg, floors). Most US Environmental Protection Agency (EPA)-registered hospital disinfectants should adequately inactivate pathogens, such as MRSA and VRE. Cleaning of curtains is recommended when they are visibly soiled.

At our hospital, MRSA patients are in private rooms but they may also leave their rooms. They have access to the hallway vending machines, cafeteria, etc. Doesn't this contaminate the environment, especially if patients don't comply with precautions? The HICPAC 2006 guideline, Management of Multidrug Resistant Organisms in Healthcare Settings, recommends that, if MRSA colonized or infected patients do not have draining wounds, diarrhea, or uncontrolled secretions, healthcare organizations should establish ranges of permitted ambulation, socialization, and use of common areas on the basis of their risk to other patients and on the ability of the colonized or infected patients to observe proper hand hygiene and other recommended precautions to contain secretions and excretions.[8] Noncompliant patients should be confined to their rooms.

We are seeing more patients in the home health setting with a history of MRSA. Clinicians are asking about self-protection and would like guidance about the level of precautions that they should take. There are 2 issues in the home health setting, just as there are in the hospital. How do caregivers protect themselves, and how do they prevent transmitting the bacteria to other patients in their care? Many home healthcare patients are at increased risk for infection because of the presence of wounds, invasive tubes and catheters, or conditions that result in a compromised immune system.

The primary means to prevent transmission from a colonized or infected patient is through diligent hand hygiene. Hands should be cleaned before entering the home, after removing gloves, and before leaving the home. The home healthcare professional should carry both antiseptic soap for washing hands under running water and alcohol-based hand gel. Home health nurses should follow standard precautions when caring for patients colonized or infected with pathogens, such as MRSA, which means wearing gloves for contact with blood or body fluids, secretions, excretions, mucous membranes, and nonintact skin. Gloves should be worn when changing dressings, and a gown if there is a risk for clothing coming into contact with wounds or other sources of contamination. In addition, protective eyewear is appropriate for procedures likely to generate splashes or sprays of body fluids. Soiled dressings should be disposed of carefully to prevent contamination. This can be accomplished by first placing the soiled dressing in a plastic zipper-type bag, and then putting it into the trash.

Common sense dictates that even though the setting is different, the principles used to prevent transmission remain the same. A nurse would not sit on the bed of a patient on contact precautions with an MRSA-colonized wound in the hospital and should not do so in the home.[8] Other efforts should be focused on preventing cross-transmission of a MDRO via the nurse's clinical bag, clothing, or equipment that are carried from home to home. Supplies and equipment should be dedicated for the patient, when possible. When not possible, reusable equipment must be cleaned with a hospital-grade disinfectant. Supplies and equipment should be removed from the bag before gloving so that there is no need to reach into the equipment bag with a contaminated hand.[9] Alternatively, the bag can be left in the car and the necessary supplies taken into the home. Reusable equipment that must be cleaned outside of the home should be placed in a plastic bag for transport out of the home for subsequent cleaning and disinfection.[8]

What about clients with VRE or MRSA who are cared for at home under hospice care? Nurses and caregivers may not be aware of the patient's MRSA- or VRE-positive status and only general precautions are used. There is no special cleaning in the home or careful handwashing by family, and no surface cleaning of bathrooms or light switches, etc. The patient is also in contact with family, children, and infants at home. In a patient's own home, the most important infection control measure is good handwashing by all household members. Healthy family members may have patient contact as long as hand hygiene is practiced.

Healthcare professionals should always be told whether a patient is colonized or infected with a MDRO, such as MRSA or VRE. The precautions that should be taken by healthcare professionals are the same as those for home healthcare.

The CDC recommends the following precautions for family caregivers of infected persons in their homes[10]:

Caregivers should wash their hands with soap and water after physical contact with the infected or colonized person and before leaving the home;


Towels used for drying hands after contact should be used only once;


Disposable gloves should be worn if contact with body fluids is expected, and hands should be washed after removing the gloves;


Linens should be changed and washed if they are soiled as well as on a routine basis;


The patient's environment should be cleaned routinely and when soiled with body fluids; and


Notify physicians and other healthcare personnel who provide care for the patient that the patient is colonized with an MDRO.


What is the best way to attempt to eliminate colonization in a patient? In a prison setting, is it necessary to place the patient in a strict lockdown with no contact with others, or can they be in the general population as long as a wound is covered? There is debate about the best way to decolonize a patient, or indeed whether it is even a good idea to attempt to do so. Most existing protocols for decolonization suggest 5 days of mupirocin ointment to the nares along with 5 days of chlorhexidine showers. However, Staphylococcus can quite easily develop resistance to mupirocin, so the overuse of decolonization could lead to increased resistance of MRSA to mupirocin. Elizabeth Bancroft, MD, SM, Medical Epidemiologist with the Los Angeles County Department of Health, discourages practitioners from attempting decolonization in patients except in the situation of recurrent infections without an ongoing source of MRSA. Her rationale is that there is no point in trying to decolonize someone who is constantly coming into contact with MRSA because of their environment or because of risky behaviors.

Decolonization is sometimes attempted in a group of people but only when there is a closed cohort, such as a day care, household, or athletic team, with ongoing continued transmission of MRSA. When group decolonization is being considered, surveillance cultures prior to decolonization from all group members are probably unnecessary because nasal swabs are not 100% sensitive. All group members should undergo the decolonization regimen simultaneously.[11]

Prison inmates with MRSA do not need to be isolated as long as the wound or source of infection can be contained. With wounds, this means that the inmate is able to keep a clean, dry bandage over the wound and is taught proper hygienic disposal of bandages. The soiled bandage should be placed in a plastic zipper-type bag before being placed in the regular trash. If the inmate has MRSA in the urine and is incontinent, isolation is necessary, but if they are continent, then interaction with the general population is permitted. These recommendations are based on practicality (isolation beds are very limited in a correctional facility), needs of the inmates for socialization, needs of the correctional facility to free up resources and staff, and lack of evidence that strict isolation is required in correctional facilities to control the transmission of MRSA. The biggest challenge now to correctional facilities, according to Dr. Bancroft, is the continued importation of MRSA from the outside.

School nurses are beginning to see CA-MRSA in the school system. Physicians are sometimes remiss in having the families notify the schools, and we generally find out about the diagnosis from neighbors and other parents! What policies should the school put into effect to protect other students, especially those who are immunocompromised? Recommendations include contacting your state department of health to see whether they already have guidelines or policies in place for handling MRSA and VRE in your state's schools. (See State Health Agencies for links to all state health departments.) Many states already have such guidelines. Although not identical, the guidelines are very similar in many respects. Children who are colonized with MRSA should not be excluded from the classroom. Open, draining wounds should be covered with clean, dry bandages. If bandages are changed at school, they must be disposed of in a manner that does not expose others to contamination. Persons who provide wound care should wear gloves and practice diligent handwashing.

Some state health departments also have policies in regard to the placement of students with MRSA colonization or infections in classrooms with students who have medical conditions resulting in immune system suppression. There may also be specific guidelines in regard to the exclusion from the classroom of students with MRSA or VRE who also have possible symptoms of infection, such as fever, cough, rash, or diarrhea.

Transmission of MRSA among sports participants is another concern. Close physical contact, a break in the skin, and sharing of equipment and clothing place young athletes at increased risk for MRSA acquisition. CDC measures for preventing MRSA transmission among sports participants include[12]:

Cover all wounds. If a wound cannot be covered adequately, consider excluding players with potentially infectious skin lesions from practice or competitions until the lesions are healed or can be covered adequately.


Encourage good hygiene, including showering and washing with soap after all practices and competitions.


Ensure availability of adequate soap and hot water.


Discourage sharing of towels and personal items (eg, clothing or equipment).


Establish routine cleaning schedules for shared equipment.


Train athletes and coaches in first aid for wound and recognition of wounds that are potentially infected.


Encourage athletes to report skin lesions to coaches and encourage coaches to assess athletes regularly for skin lesions.


When MRSA infection is suspected, students should be referred to their primary care provider for evaluation and treatment.

What guidelines are there to prevent the spread of MRSA in long-term care facilities? Can long-term care facilities refuse to accept patients with MRSA? In long-term care facilities, colonized and infected residents serve as the primary reservoirs of MRSA. Asymptomatic colonization of residents' nares is common and difficult to eradicate, even with treatment. Long-term care facilities can safely care for and manage MRSA patients by following appropriate infection control practices. In addition, long-term care facilities should be aware that persons with MRSA, VRE, and other infections may be protected by the Americans with Disabilities Act or other applicable state or local laws or regulations.

The most important component of an infection control program for a long-term care facility is education of staff members with regard to hand hygiene. In making decisions on whether to use contact precautions, one reasonable strategy is to consider the individual patient's clinical situation. For independent residents, one approach is to follow standard precautions, making sure that gloves and gowns are used for contact with uncontrolled secretions, pressure ulcers, draining wounds, stool incontinence, and ostomy tubes/bags. For patients who are totally dependent on healthcare personnel for care and activities of daily living, and for those whose infected secretions or drainage cannot be contained, contact precautions in addition to standard precautions may be more appropriate.

As a rule, long-term care residents who are colonized with MRSA and who do not have draining wounds, diarrhea, or uncontrolled secretions should not be placed in strict isolation or restricted from dining rooms or group activities in an attempt to control transmission of MRSA. Such patients should be permitted to participate in group meals and activities if wounds are covered, bodily fluids are contained, and the patients observe good hygienic practices.

Can a pregnant woman who has frequent bouts with MRSA pass the infection on to her fetus? Approximately 5% to15% of women of childbearing age carry S aureus in their vagina.[13] Some recent studies have identified a low prevalence of MRSA in vaginal-rectal cultures obtained to screen for group B streptococcal colonization during late pregnancy.[14] S aureus can be transmitted from the maternal genital tract to the fetus or newborn during pregnancy, labor, or delivery, but this type of transmission leading to serious infection or other adverse outcomes appears to be rare.[15] There are no recommendations to routinely screen pregnant women for S aureus or MRSA colonization or to attempt decolonization in pregnant women with a history of MRSA infection.

Decolonization is sometimes considered in a patient (pregnant or otherwise) with a history of recurrent MRSA infections that are unresponsive to other measures. Vaginal delivery and breastfeeding are not contraindicated in a woman with MRSA colonization or infection. Active lesions should be kept covered with clean, dry bandages, and women should wash their hands well, particularly after changing wound dressings and before touching their newborn. Obstetrics departments should follow their hospital policy in regard to infection control practices for patients who are known or suspected to be infected or colonized with MRSA.

What precautions should healthcare workers, such as nurses, take if they have been treated for an MRSA infection? Is it safe for them to continue taking care of patients? Nurses and other healthcare workers who do not have active infections or who have wounds that can be covered and controlled with dressings are permitted to work. Colonization alone does not prevent healthcare workers from working unless they are epidemiologically linked to transmission of an infection. The new HICPAC guideline recommends obtaining cultures of healthcare personnel for target MDROs only when there is epidemiologic evidence linking the healthcare staff member to ongoing transmission.[8]

References
Boyce JM. Diagnosis and treatment of serious antimicrobial resistant Staphylococcus aureus infection. Clin Updates Infect Dis. 1998;4.
Muto CA, Jernigan JA, Ostrowsky BE, et al. SHEA guideline for preventing nosocomial transmission of multidrug-resistant strains of Staphylococcus aureus and Enterococcus. Infect Control Hosp Epidemiol. 2003;24:362-386. Available at: http://www.shea-online.org/Assets/fi...A_MRSA_VRE.pdf Accessed October 13, 2006.
Huang SS, Yokoe DS, Hinrichsen VL, et al. Impact of routine intensive care unit surveillance cultures and resultant barrier precautions on hospital-wide methicillin-resistant Staphylococcus aureus bacteremia. Clin Infect Dis. 2006;43:971-978. Abstract
Moran GJ, Krishnadasan A, Gorwitz RJ, et al. Methicillin-resistant S. aureus infections among patients in the emergency department. N Engl J Med. 2006;355:666-674. Abstract
Leijten DT, Rejger VS, Mouton RP. Bacterial contamination and the effect of filters in anaesthetic circuits in a simulated patient model. 1992;21:51-60.
Langevin PB, Rand KH, Layon AJ. The potential for dissemination of Mycobacterium tuberculosis through the anesthesia breathing circuit. Chest. 1999;115:1107-1114. Abstract
Tablan OC, Anderson LJ, Besser R, Bridges C, Hajjeh R. Guidelines for preventing health-care associated pneumonia, 2003. MMWR Recomm Rep. 2004;53:1-36.
Siegel JD, Rhinehart E, Jackson M, Chiarello L; Healthcare Infection Control Practices Advisory Committee. Management of multi-drug resistant organisms in healthcare settings, 2006. US Centers for Disease Control and Prevention. Available at: http://www.cdc.gov/ncidod/dhqp/pdf/a...deline2006.pdf Accessed October 19, 2006.
Boling PA. The health care worker, resistant bacteria (MRSA) and preventing contagion. Clin Geriatr. 2004;12:17-20.
US Centers for Disease Control and Prevention. Multidrug-resistant organisms in non-hospital healthcare settings. December 2000. Available at: http://www.cdc.gov/ncidod/dhqp/ar_multidrugFAQ.html Accessed October 23, 2006.
Gorwitz RJ, Jernigan DB, Powers JH, Jernigan JA. Strategies for clinical management of MRSA in the community: summary of an experts' meeting convened by the Centers for Disease Control and Prevention. 2006. Available at: http://www.cdc.gov/ncidod/dhqp/ar_mr...04meeting.html Accessed October 6, 2006.
Gantz N, Harmon H, Handy J, et al. Methicillin-resistant Staphylococcus aureus infections among competitive sports participants -- Colorado, Indiana, Pennsylvania, and Los Angeles County, 2000-2003. MMWR. 2003;52;793-795.
Guinan ME, Dan BB, Guidotti RJ, et al. Vaginal colonization with Staphylococcus aureus in healthy women. Ann Intern Med. 1982;96:944-947. Abstract
Andre P, Thebaud B, Guibert M, et al. Maternal-fetal Staphylococcal infections: a series report. Am J Perinatol. 2000;17:4237.
Chen KT, Huard RC, Della-Latta P, Saiman L. Prevalence of methicillin-sensitive and methicillin-resistant Staphylococcus aureus in pregnant women. Obstetr Gynecol. 2006;108:482-487.


Suggested Readings
Harbarth S, Masuet-Aumatell C, Schrenzel J, et. al. Evaluation of rapid screening and pre-emptive contact isolation for detecting and controlling methicillin resistant Staphylococcus aureus in critical care. Crit Care. 2006;10:R25. Available at: http://www.medscape.com/viewarticle/523530 Accessed October 6, 2006.
Turabelidze G, Lin M, Wolkoff B, Dodson D, Gladbach S, Bao-Ping Z. Personal hygiene and methicillin-resistant Staphylococcus aureus infection. Emerg Infect Dis. 2006;12:422-427. Available at: http://www.medscape.com/viewarticle/525120 Accessed October 23, 2006.

Related Resources


Association for Professionals in Infection Control and Epidemiology. Available at: http://www.apic.org/ Accessed October 23, 2006.
The Society for Healthcare Epidemiology of America. Drug resistant organisms. Available at: http://www.shea-online.org/news/mdros.cfm Accessed October 23, 2006.
US Centers for Disease Control and Prevention. MRSA in healthcare settings. Available at: http://www.cdc.gov/ncidod/dhqp/ar_mr...ight_2006.html Accessed October 23, 2006.





Laura Stokowski, RN, MS, Staff Nurse, Inova Fairfax Hospital for Children, Falls Church, Virginia; Editor, Medscape Ask the Experts Advanced Practice Nurses


Disclosure: Laura A. Stokowski, RN, MS, has disclosed no relevant financial relationships.


Medscape Nurses. 2006;8(2) ©2006 Medscape







Discussions
Join a Discussion with your colleagues

[Anita]

Hello Everyone,

I have discussed this at length with Dr. Bertagnoli and Dr. Fenk-Mayer. Both the St. Elisabeth Klinikum in Straubing and Krieskrankenhaus in Bogen are "certified MRSA FREE".

Personally, I have always been impressed with the infection control within these two facilities from day one.

What it boils down to is, All operating personnel remain within the contained OR area. When the day is done, clothes and shoes are completely changed and only street clothes are worn outside of the OR area.

Combine that with exemplary sterlization techniques,as well as the overall hospital personnel being religious regarding cleaning rooms and equipment, all of that amounts to a low to zero infection rate of any kind and certainly not MRSA.

I have lived here for 15 months and its obviously clear this is not an antibiotic based society, they are used, of course, when needed, but not issued prophylatically as often as in the states.

Just my observations from Straubing.

Oh, and Alastair, seeing as how we are both sincerely partial for very good reasons, I personally have to differ on just which Dr. has done the most implantations. Just a playful rivalry intended.

Vielen Danke

Anita Peludat

[Alastair]

Hi Anita,
If both Dr B and Zeegers have done over 2000 surgeries as I believe, it doesn`t really matter which Dr does your surgery unless you have a preference for ones aftershave -- - - lol
Best
Alastair

[Harrison]

Anita, thanks for the clarification. Alastair, thanks for the very "meaty" article. Not to beat this infection issue to death, but the op-ed section of the NYT had some new details on how poorly the U.S. is handling the spread of MRSA.
__________________________________________

November 14, 2006
Op-Ed Contributor
To Catch a Deadly Germ
By BETSY McCAUGHEY

WHAT kills more than five times as many Americans as AIDS? Hospital infections, which account for an estimated 100,000 deaths every year.

Yet the Centers for Disease Control and Prevention, which are calling for voluntary blood testing of all patients to stem the spread of AIDS, have chosen not to recommend a test that is essential to stop the spread of another killer sweeping through our nation’s hospitals: M.R.S.A., or methicillin-resistant Staphylococcus aureus. The C.D.C. guidelines to prevent hospital infections, released last month, conspicuously omit universal testing of patients for M.R.S.A.

That’s unfortunate. Research shows that the only way to prevent M.R.S.A. infections is to identify which patients bring the bacteria into the hospital. The M.R.S.A. test costs no more than the H.I.V. test and is less invasive, a simple nasal or skin swab.

Staph bacteria are the most prevalent infection-causing germs in most hospitals, and increasingly these infections cannot be cured with ordinary antibiotics. Sixty percent of staph infections are now drug resistant (that is, M.R.S.A.), up from 2 percent in 1974.

Some people carry M.R.S.A. germs in their noses or on their skin without realizing it. The bacteria do not cause infection unless they get inside the body — usually via a catheter, a ventilator, or an incision or other open wound. Once admitted to a hospital, these patients shed the germs on bedrails, wheelchairs, stethoscopes and other surfaces, where M.R.S.A. can live for many hours.

Doctors and other caregivers who lean over an M.R.S.A.-positive patient often pick up the germ on their hands, gloves or lab coats and carry it along to their next patient.

The blood-pressure cuffs that nurses wrap around patients’ bare arms frequently carry live bacteria, including M.R.S.A. In a recent study at a French teaching hospital, 77 percent of blood-pressure cuffs wheeled from room to room were contaminated. Another study linked contaminated blood-pressure cuffs to several infected infants in the nursery at the University of Iowa hospital.

Among developed nations, the United States has one of the worst records of curbing drug-resistant infections, according to the Sentry Antimicrobial Surveillance Program, an international effort to monitor drug-resistant germs. In this country, M.R.S.A. hospital infections increased 32-fold from 1976 to 2003, according to the C.D.C.

In the 1980s, Denmark, Finland and the Netherlands faced similarly soaring rates of M.R.S.A., but nearly eradicated it. How? By screening patients and requiring health care workers treating patients with M.R.S.A. to wear gowns and gloves and use dedicated equipment to prevent the spread. The Dutch called their strategy “search and destroy.”

A growing number of hospitals in the United States have proved that such precautions work here, too. Recently, a pilot program using screening at Presbyterian University Hospital, in Pittsburgh, reduced M.R.S.A. infections by 90 percent. At a Yale-affiliated hospital in New Haven, screening reduced M.R.S.A. infections in intensive care by two-thirds.

And a recently completed nine-year study at the Brigham and Women’s Hospital, in Boston, found that screening led to a 75 percent drop in M.R.S.A. bloodstream infections among intensive-care patients and a 67 percent decline throughout the hospital. Earlier efforts to stop these infections by installing many more dispensers of hand cleanser and conducting a yearlong educational campaign on hand hygiene had no effect.

Some public health advocates recommend screening only “high-risk” patients — those who recently have been hospitalized, live in nursing homes or have kidney disease. Partial screening is somewhat effective, but universal screening prevents the most infections.

Can hospitals afford to screen for M.R.S.A.? They cannot afford not to. Infections wipe out hospital profits. When a patient develops an infection and has to spend many additional weeks hospitalized, Medicare does not pay for most of that additional care.

Treating hospital infections costs an estimated $30.5 billion a year in the United States. Prevention, on the other hand, is inexpensive and requires no capital outlays. A pilot program at the University of Pittsburgh found that screening tests, gowns and other precautions cost only $35,000 a year, and saved more than $800,000 a year in infection costs. A review of similar cost analyses, published in The Lancet in September, concluded that M.R.S.A. screening increases hospital profits — as it saves lives.

Yet, for a decade, the C.D.C. has rebuffed calls for screening, most recently from a committee of the Society for Healthcare Epidemiologists of America. C.D.C. officials claim that more research is needed to prove the benefits of screening. More research cannot hurt, but we know enough already to move ahead.

Some hospitals are leading the way, including Evanston Northwestern, in Illinois; the Veterans Affairs medical centers; New England Baptist Hospital, in Boston; and Johns Hopkins Hospital, in Baltimore.

The C.D.C.’s lax guidelines give many other hospitals an excuse to do too little. Every year of delay costs thousands of lives and billions of dollars.

Betsy McCaughey, a former lieutenant governor of New York, is the founder of the Committee to Reduce Infection Deaths.