Staphylococcus aureus decolonisation—treatment to eradicate staphylococcal carriage—is often considered as a measure to prevent S aureus infection. The most common approach to decolonisation has been intranasal application of mupirocin either alone or in combination with antiseptic soaps or systemic antimicrobial agents. Some data support the use of decolonisation in surgical patients colonised with S aureus, particularly in those undergoing cardiothoracic procedures. Although this intervention has been associated with low rates of postoperative S aureus infection, whether overall rates of infection are also decreased is unclear. Patients undergoing chronic haemodialysis or peritoneal dialysis might benefit from decolonisation, although repeated courses of treatment are needed, and the effects are modest. Eradication of meticillin-resistant S aureus (MRSA) carriage has generally been difficult, and the role of decolonisation as an MRSA infection control measure is uncertain. The efficacy of decolonisation of patients with community-associated MRSA has not been established, and the routine use of decolonisation of non-surgical patients is not supported by data.

Read more: http://www.mdlinx.com/infectious-disease/news-article.cfm/3842832/staphylococcal-infections#ixzz1kFwDbDBA

The Lancet Infectious Diseases, Volume 11, Issue 12, Pages 952 – 962, December 2011

Recent findings: Combination therapy with vancomycin–rifampin, although associated with better cure rates, resulted in the emergence of high rates of rifampin resistance. Of the newer anti-methicillin-resistant Staphylococcus aureus (MRSA) antibiotics, ceftopibrole, ortivancin and dalbavancin require further development prior to a further assessment by the United States Food and Drug Administration. Ceftaroline, telavancin and daptomycin were associated with comparable clinical cure rates compared with vancomycin in the treatment of complicated MRSA skin and soft tissue infections. In the treatment of hospital-acquired pneumonia, both telavancin and linezolid resulted in significantly greater clinical cure rates compared with vancomycin. Despite greater clinical cure rates, no difference in overall or infection-related mortality was detected. Of concern is the appearance of daptomycin and linezolid resistance following increased use. Toxicity profiles (especially of linezolid) are comparable to vancomycin provided short-duration therapy is prescribed. The first reports of daptomycin-induced acute eosinophillic pneumonia were described in 2010.

Summary: Based on current evidence, greater microbiological and clinical cure rates are achieved with alternative agents. However, these differences do not translate into mortality benefits compared with vancomycin for the treatment of S. aureus infections.
Current Opinion in Infectious Diseases: December 2011 – Volume 24 – Issue 6 – p 515–520

Read more: http://www.mdlinx.com/infectious-disease/news-article.cfm/3860339/methicillin-resistant-staphylococcus-aureus#ixzz1kFr7GjFO
BMC Infectious Diseases 2011, 11:335 doi:10.1186/1471-2334-11-335

Methods
Patients with MRPA isolates were prospectively identified (January 2006-May 2008). A combined surveillance procedure (environmental survey, and active surveillance program in intensive care units [ICUs]) and an infection control strategy (closure of ICU and urology wards for decontamination, strict compliance with cross-transmission prevention protocols, and a program restricting the use of carbapenems in the ICUs) was designed and implemented.

Results
Three hundred and ninety patients were identified. ICU patients were the most numerous group (22%) followed by urology patients (18%). Environmental surveillance found that 3/19 (16%) non-ICU environmental samples and 4/63 (6%) ICU samples were positive for the MRPA clonal strain. In addition, active surveillance found that 19% of patients were fecal carriers of MRPA. Significant changes in the trends of incidence rates were noted after intervention 1 (reinforcement of cleaning procedures): -1.16 cases/1,000 patient-days (95%CI -1.86 to -0.46; p = 0.003) and intervention 2 (extensive decontamination): -1.36 cases/1,000 patient-days (95%CI -1.88 to -0.84; p < 0.001) in urology wards. In addition, restricted use of carbapenems was initiated in ICUs (January 2007), and their administration decreased from 190-170 DDD/1,000 patient-days (October-December 2006) to 40-60 DDD/1,000 patient-days (January-April 2007), with a reduction from 3.1 cases/1,000 patient-days in December 2006 to 2.0 cases/1,000 patient-days in May 2007. The level of initial carbapenem use rose again during 2008, and the incidence of MRPA increased progressively once more.

Conclusions
In the setting of sustained MRPA outbreaks, epidemiological findings suggest that patients may be a reservoir for further environmental contamination and cross-transmission. Although our control program was not successful in ending the outbreak, we think that our experience provides useful guidance for future approaches to this problem.

BMC Infectious Diseases 2011, 11:272doi:10.1186/1471-2334-11-272

Diagnostic Microbiology & Infectious Disease Volume 71, Issue 4 , Pages 408-414, December 2011

J Am Board Fam Med September-October 2011 vol. 24 no. 5 524-533

Journal of Clinical Microbiology, 08/31/2011 published August 2011, doi: 10.1128/​JCM.00531-11
JCM.00531-11

Staphylococcus aureus bacteraemia (SAB) is a leading cause of mortality and morbidity in both nosocomial and community settings. The objective of the study is to explore epidemiological characteristics and predisposing risk factors associated with healthcare-associated (HCA) and community-acquired (CA) SAB, and to evaluate any differences in mortality and efficacy of initial antimicrobial therapy on treatment outcome. We conducted a two-part analysis. First, a triple case–control study in which groups of HCA SAB with onset ≥48 h after hospital admission (HCA ≥48 h), HCA SAB with onset <48 h of hospital admission (HCA <48 h), and CA SAB were compared with controls. Second, a cohort study including all patients with SAB was performed to identify factors associated with in-hospital mortality. SAB was diagnosed in 165 patients over the study period (January 2007 to December 2007). Five variables were independently associated with HCA ≥48 h SAB: presence of central venous catheter, solid tumour, chronic renal failure, previous hospitalization and previous antibiotic therapy. Significant risk factors for HCA <48 h SAB were: Charlson Comorbidity Index ≥3, previous hospitalization, living in long-term care facilities and corticosteroid therapy. Factors independently associated with CA SAB were: diabetes mellitus, HIV infection and chronic live disease. Patients with HCA <48 h SAB were significantly more likely to receive initial inadequate antimicrobial treatment than patients with CA or HCA ≥48 h SAB (44.8% versus 33.3% and 31.5%, respectively). Logistic-regression analysis identified three variables as independent predictors of mortality: presentation with septic shock, infection with methicillin-resistant S. aureus, and initial inadequate antimicrobial treatment. More than half of patients with SAB have MRSA strains and presentation with septic shock, and inappropriate empirical therapy was associated with increased mortality.
Clinical Microbiology and InfectionArticle first published online: 14 OCT 2011 DOI: 10.1111/j.1469-0691.2011.03679.x

Methods: Culture-proven episodes were identified prospectively from neonatal units participating in the neonatal infection surveillance network. Demographic, risk factor, and outcome data were collected.

Results: Between 2004 and 2009, there were 117 episodes of SA infections (including 8 methicillin-resistant SA) in 116 infants from 13 units. The median gestational age and birth-weight were 27 weeks (90% ≤37 weeks, 85% ≤32 weeks) and 850 g (90% ≤2500 g), respectively. The overall incidence was 0.6 per 1000 live births and 23/1000 in infants <1500 g. Most episodes (94%) occurred more than 48 hours after birth (late onset). There were 7 early-onset episodes (<48 hours) (median gestational age, 38.5 weeks), all due to methicillin-susceptible SA. At the time of culture, 67 of 95 (71%) infants were receiving respiratory support and 47 of 94 (50%) had a central line in situ. The majority of infants had nonspecific clinical features although evidence of focal infection (skin, soft tissue, bone, joint, or pneumonia) was ultimately seen in 41 of 91 (45%). There were 18 deaths, 4 (all late onset) directly due to methicillin-susceptible SA sepsis (4.4%).

Conclusions: SA is the second most common pathogen causing late-onset neonatal infections in this neonatal network. Infants who weigh <1500 g in intensive care settings are the most vulnerable group. Clinical signs are not sufficiently distinctive to allow targeted therapy, suggesting that an antistaphylococcal agent should be part of empiric therapy for late-onset sepsis in premature infants.

Pediatric Infectious Disease Journal: October 2011 – Volume 30 – Issue 10 – pp 850-854

Epidemiology
The nares are commonly colonized by S. aureus. Approximately 20% of individuals are chronically colonized with a single strain of S. aureus, and are called persistent carriers. A large proportion of the population (60%) harbors S. aureus intermittently, and the strains change with varying frequency. Such people are called intermittent carriers. Finally, a minority of patients (20%) almost never carries S. aureus and are called noncarriers. Persistent carriage is more common in children than adults, and many people change their pattern of carriage between the age of 10 and 20 years. The reasons for these patterns are unknown. Persistent carriage seems to have a protective effect on the acquisition of other strains during hospitalization (3). However, carriers are 2 to 9 times more likely to acquire S. aureus SSI’s than noncarriers. In fact, nasal carriage is the only independent risk factor for S. aureus SSI in patients undergoing orthopaedic implant surgery (4, 5). Although the prevalence of nasal carriage may vary depending on the population, many studies show an increase in colonization by methicillin-resistant S. aureus (MRSA) over the past decade.

Evidence of Effectiveness of Decolonization Regimens
Although staphylococci are common inhabitants of the skin and mucus membranes, the anterior nares provide the principal reservoir for these organisms (6). There is a strong epidemiologic association between nasal carriage of S. aureus and development of S. aureus SSI’s. Carriage of MRSA constitutes a special problem with regard to prevention and treatment of infection. Elimination of nasal carriage would theoretically reduce the infection rates in populations in which it has been identified as a risk factor (3). When the nares are treated topically to eliminate nasal carriage, in most cases the organism also disappears from other areas of the body. In a study performed by Ammerlann et al. (7) short-term nasal application of mupirocin was the most effective treatment for eradicating methicillin-resistant S. aureus carriage, with an estimated success rate of 90% 1 week after treatment and approximately 60% after a longer follow-up period.

Colonization of Providers
Physicians have a higher prevalence of MSSA colonization compared to the general population but an equivalent prevalence of MRSA. Studies have shown that 10-15% of healthy adults carry S. aureus in their nares; this figure rises to 20-35% in hospital personnel (6, 8). This puts hospital personnel at risk for developing SSI’s during their own elective surgery and raises concerns about spread to patients under their care.
A study by Vonberg et al (9) showed 3% of MRSA outbreaks were caused by asymptomatic colonized healthcare workers and demonstrated that healthcare workers are capable of transmitting MRSA to others making colonization a potential concern. Other studies have shown that the incidence of nasal colonization with S. aureus among attending orthopaedic physicians is similar to the prevalence found in their high risk patient population. The prevalence of S. aureus in the residents was even greater than the attendings. This is postulated to the amount of time residents spend in the hospital on the floors caring for patients (10). It is known that different surgeons can have different infection rates, and it has been shown that infection surveillance of individual surgeons leads to lower infection rates (11). However there is no evidence to suggest that nasal decolonization of surgeons is effective in preventing SSI’s in patients.

Evidence that Decolonization Reduces SSI Rates
(See Table 1)
A randomized double-blinded, placebo-controlled multi-center trial by Bode et al. (12) demonstrated a decrease in the rate of deep SSI’s acquired in the hospital following rapid screening and decolonization on admission of nasal carriers of S. aureus. A total of 1,270 nasal swabs from 1,251 patients were positive for S. aureus, of these 917 were enrolled in the intention-to-treat analysis, with 808 (88.1%) undergoing a surgical procedure. The rate of S. aureus infection was 3.4% (17 of 504 patients) in the decolonized group, as compared with 7.7% (32 of 413 patients) in the placebo group that was not decolonized (P=0.005). The authors concluded that the number of surgical-site S. aureus infections acquired in the hospital can be reduced by rapid screening and decolonizing of nasal carriers of S. aureus on admission. Germatt et al. (13) studied the effect of prophylactic mupirocin treatment in the orthopedic population in an unblinded interventional trial. The wound infection rates were 14/1,044 in the intervention group treated with mupiricon, and 34/1,260 in the control group not treated with mupirocin (P = 0.02). A prospective observational study of decolonized patients performed by Rao et al. (14) found the overall infection rate, including nonstaphylococcal infections, decreased from 2.6% during the preintervention period to 1.5% during the intervention period (P=0.02) and concluded that preoperative nasal decolonization is a safe way to reduce S. aureus SSI’s in patients undergoing TJA.

Two additional studies performed by Kluytmans et al. in non-orthopaedic populations also found nasal decolonization using mupirocin ointment to be effective in reducing S. aureus infections. The first study by Kluytmans et al. (15) consisted of a historical control group and an intervention group of cardiothoracic surgery patients. The historical control group consisted of 928 patients and the intervention group of 868, of whom 752 were treated with mupirocin. In the intention-to-treat analysis, a significant reduction in SSI rate was observed after the intervention (historical-control group 7.3% and intervention group 2.8%; (P < .0001). The SSI rate in the concurrent control group was also significantly higher than in the treated group (7.8% and 2.0%, respectively; P = .0023). They concluded that perioperative elimination of nasal carriage using mupirocin nasal ointment significantly reduces the SSI rate in cardiothoracic surgery. The second study was comprised of 226 hemodialysis patients, of whom 172 were evaluated to determine the efficacy of mupirocin on preventing bacteremia (16). Sixty-seven (39%) were identified as nasal carriers. Following the initial treatment, 66 nasal cultures (98.5%) became negative. After 3 months and 6 months, respectively, 63 (94%) and 61 (91%) of the treated carriers had negative cultures. The rate of bacteremia (defined as the number of episodes of S. aureus bacteremia per patient-year on hemodialysis) was significantly lower among the 226 patients in the study group (0.04 per patient-year) than among the 273 patients in the control group (0.25 per patient year, P < .001). They concluded mupirocin nasal ointment effectively eliminates nasal carriage of S. aureus in patients on hemodialysis and reduced the incidence of bacteremia in this population.

Financial Implications of Surgical Site Infections
Total joint and spine fusion patients are orthopaedic populations at high risk for infection. There were approximately 658,000 primary joint arthroplasties performed in the United States in 2005 and 79,000 revisions in the same year. This number is projected to rise to 4 million primary arthroplasties and 375,000 revisions by the year 2030. Infection rates after hip and knee arthroplasty were reported to be 1.7% and 2.1%, respectively, when post discharge surveillance was conducted, and the percentage of revisions that were the result of deep infections was estimated at 8.4% for hips and 16.8% of knees in 2005 (1). The proportion of revisions due to infection is projected to rise for the next 25 years, and the economic burden of infections is expected to exceed 50% of the inpatient resources available for revision arthroplasties in 2016 and 2030 for total hips and knees, respectively. Simultaneously, according to the Healthcare Cost and Utilization Project databases, the number of spinal fusion procedures had an exponential increase of 73%, from 202,100 procedures performed in 1997 to 349,400 procedures in 2005. The incidence of postoperative spine infections has been reported to be as high as 15%, with higher risks noted for revision spinal surgeries. The average cost of a septic joint revision is $70,000 and the average cost of treating a spine infection is $100,000 (see Figure 2). Therefore, successful efforts to reduce infections associated with these procedures are likely to have a significant impact. A decision analysis study demonstrated this potential cost savings with screening and decolonization of patients before elective arthroplasty and spine fusion procedures. Comparing the cost of screening to the cost of infection investigators found screening and decolonization became cost effective when the relative rate of SSI decreases by just 10% (1). This effect is due to the high cost of treating SSI’s after these high risk orthopaedic procedures in comparison to the low cost of a screening and decolonization program (1).

NYUHJD Algorithm for Decolonization
Our institution implemented a S. aureus screening and decolonization program for patients undergoing primary hip or knee arthroplasty and spine fusion (see Figure 1). All patients who went through the hospital’s pre-admission testing program participated in the study. Patients were given a prescription for mupirocin ointment and received a nasal culture preoperatively. If the patient complied with the mupirocin treatment and the nasal cultures were positive for MRSA, they received peri-operative antibiotic prophylaxis with vancomycin. In addition, they received in hospital decolonization with mupirocin and were treated with isolation precautions after surgery to protect against the spread of MRSA in the hospital. If they were noncompliant and had cultures positive for MSSA, they were treated peri-operatively with traditional prophylaxis with a cephalosporin and were decolonized peri-operatively with mupirocin. All patients with negative cultures for both MRSA and MSSA received traditional cephalosporin treatment perioperatively (1).

NYUHJD Results and Acceptance of Algorithm for Decolonization
As seen in the study by Kim et al. implementation of an institution wide prescreening program for the identification and eradication of MRSA carrier status of patients undergoing elective orthopaedic surgery is feasible and can lead to significant reductions in postoperative rates of surgical site infections (2). At our institution we investigated the effects of implementation of an institution wide screening, decolonization and prophylaxis protocol on the rates of SSI’s in patients undergoing primary knee and hip arthroplasties. 2,058 patients were enrolled in the study, 1,644 patients were in the treatment group and 414 were in the concurrent control group. The treatment group attended pre-operative admission testing (PAT) clinic where they were screened for MSSA and MRSA colonization. All patients were provided a 5-day course of nasal mupirocin for decolonization and a single pre-operative chlorhexidine shower. Additionally, patients colonized with MRSA received vancomycin peri-operative prophylaxis. The concurrent control group did not attend PAT or receive mupirocin treatment, they received either cefazolin or clindamycin for perioperative antibiotic prophylaxis, as their carrier status was unknown. All other peri-operative infection control measures were identical for the two groups. There were a total of 6 deep S. aureus infections in the control group (1.45%) and 21 in the treatment group (1.28%), this represented a decrease of 13% (P=0.809) in the treatment versus control group. This decrease represented an encouraging positive trend that supports the use of pre-operative colonization testing, but did not reach statistical significance due to control group sample size limitations. Therefore, further study will be needed to determine if our program demonstrates statistically significant results that are similar to those found by previous investigators. However, we did experience a significant reduction in hospital acquired MRSA infections after the decolonization program was initiated. The rate (per 1000 patient days) of hospital acquired MRSA infections was 0.05% before the decolonization program was initiated and fell to 0.029% after the initiation of our program (P= 0.007) (see Figure 3).

Patient Attitude and Compliance
We also assessed patient attitude and compliance with the decolonization program. Surgical patients at our hospital’s Pre-Admission Testing Clinic (PAT) received S. aureus reduction protocols instructing the preoperative use of chlorhexidine gluconate (CHG) soap and intranasal mupirocin ointment (MO). A survey was distributed to patients participating in the program. 81% of those who submitted survey responses indicated they had followed the MO protocol (MO users) while 89% indicated they followed the protocol for CHG (CHG users). However, 54% of MO users reported an out of pocket expense ranging from $2-$115 with a mean of $31, and 13% of MO users indicated the expense was a hard or very hard financial burden. 6% of MO users reported difficulty in locating the MO. In addition, 93% of CHG users reported CHG was very easy to use. Compliance despite potential barriers indicates a concern with infection and demonstrates a motivation for performing infection prevention measures. However, in this study, only 46% of respondents indicated a concern with SSI, suggesting further efforts at patient education are necessary. Improved compliance may be achieved if MO were provided to those patients with high out of pocket expenses or those who had difficulty purchasing or locating the product (17).

Future Directions
PCR or molecular testing may become more widely available for the screening of S. aureus colonization. Molecular testing allows rapid turnaround time and enables the physician to prescribe the decolonization regimen to only those patients who are S. aureus carriers. This may enable more discreet use of antibiotics, potentially decreasing the risk of antibiotic resistance. In addition, alternative decolonization protocols may become available due to the current expense associated with mupirocin. This substitution of povidone-iodine for mupirocin represents a significant potential cost savings as the average cost of a course of povidone-iodine is $5, while the average cost of a course of mupirocin ointment is $95, provided it can be established that it is as effective in decolonization and reducing the incidence of SSI rates with orthopaedic surgery.

Summary
Hospitals are increasingly implementing nasal screening and decolonization programs as part of their routine pre-surgical testing protocol due to mounting positive evidence that reductions in SSI rates can be achieved with this relatively low cost intervention. Screening for S. aureus infections potentially reduces the need for revision surgeries, additional hospitalizations, IV antibiotics and they may decrease the incidence of recurrent infection. However, due to the large number of patients needed to achieve statistical significance, further studies are necessary to determine the precise role and optimal protocol for screening and decolonization of S. aureus prior to high risk orthopaedic procedures.

Appendix

Table 1: Mupirocin Studies

Study

# of Patients

Type of Study

Result

Bode LG, et al.
N Engl J Med. 2010 Jan 7; 362(1):9-17.

6,771

Randomized, double-blind, placebo-controlled clinical trial

The rate of S. aureus infection was 3.4% (17 of 504 patients) in the mupirocin–chlorhexidine group, as compared with 7.7% (32 of 413 patients) in the placebo group.

Germaat-van der Sluis AJ, et al.
Acta Orthop Scand. 1998; 69:412-4.

2,304

Unblinded Intervention Trial

The wound infection rates were 14/1,044 in the intervention group and 34/1,260 in the control group (p = 0.02).

Rao N, et al.
Clin Orthop Relat Res. 2008; 466:1343-8.

636

Prospective Observational Study

The overall infection rate decreased from 2.6% during the preintervention period to 1.5% during the intervention period.

Kluytmans JA, et al.
Infect Control Hosp Epidemiol. 1996; 17:780-5.

1,796

Historical control group and intervention group

In the intention-to-treat analysis, a significant reduction in SSI rate was observed after the intervention (historical-control group 7.3% and intervention group 2.8%; P < .0001). The SSI rate in the concurrent control group was significantly higher than in the treated group (7.8% and 2.0%, respectively; P = .0023).

Kluytmans JA, et al.
Infect Control Hosp Epidemiol. 1996;17:793-7

226

Prospectively followed cohort

The rate of was significantly lower in the study group (0.04 per patient-year) than among the 273 patients in the control group (0.25 per patient year, P < .001).

Figure 1. Screening Algorithm

Figure 2. Cost Parameters

Parameter

Mupirocin Treatment

$90

Nasal Culture

$20

Vancomycin Prophylaxis

$4

Primary Total Joint

$15,000

Revision of Infected Total Joint

$70,000

Spine Surgery

$50,000

Revision of Infected Spine Surgery

$100,000

Figure 3. Comparison MRSA Rates/1000 Patients

(P=0.007)

Reference :

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Lorraine H. Hutzler,Staphylococcus aureus Screening and Decolonization and Orthopaedic Surgical Site Infection- A Review of Literature and Single Institution Experience J.Orthopaedics 2011;8(3)e8