Comparative Effectiveness of Local Application of Chlorhexidine Gluconate, Mupirocin Ointment, and Normal Saline for the Prevention of Peritoneal Dialysis-related Infections (COSMO-PD Trial): a multicenter randomized, double-blind, controlled protocol.

BACKGROUND: Current international guidelines recommend the use of a daily topical exit-site antimicrobial to prevent peritoneal dialysis (PD)-related infections. Although nonantibiotic-based therapies are appealing because they may limit antimicrobial resistance, no controlled trials have been conducted to compare topical antimicrobial agents with usual exit-site care for the prevention of PD-related infections among the Thai PD population. We propose a controlled three-arm trial to examine the efficacy and safety of a daily chlorhexidine gluconate-impregnated patch versus mupirocin ointment versus usual exit-site care with normal saline for the prevention of PD-related infections. METHODS/DESIGNS: This study is a randomized, double-blind, multicenter, active-controlled, clinical trial. Adult patients aged 18 years or older who have end-stage kidney disease and are undergoing PD will be enrolled at three PD Centers in Thailand. A total of 354 PD patients will be randomly assigned to either the 2% chlorhexidine gluconate-impregnated patch, mupirocin ointment, or usual exit-site care with normal saline dressing according to a computer-generated random allocation sequence. Participants will be followed until discontinuation of PD or completion of 24 months. The primary study outcomes are time to first PD-related infection (exit-site/tunnel infection or peritonitis) event and the overall difference in PD-related infection rates between study arms. Secondary study outcomes will include (i) the rate of infection-related catheter removal and PD technique failure, (ii) rate of nasal and exit-site Staphylococcus aureus colonization, (iii) healthcare costs, and (iv) skin reactions and adverse events. We plan to conduct a cost-utility analysis alongside the trial from the perspectives of patients and society. A Markov simulation model will be used to estimate the total cost and health outcome in terms of quality-adjusted life years (QALYs) over a 20-year time horizon. An incremental cost-effectiveness ratio in Thai Baht and U.S. dollars per QALYs gained will be illustrated. A series of probabilistic sensitivity analyses will be conducted to assess the robustness of the cost-utility analysis findings. DISCUSSION: The results from this study will provide new clinical and cost-effectiveness evidence to support the best strategy for the prevention of PD-related infections among the Thai PD population. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02547103. Registered on September 11, 2015.

Cost-effectiveness of pre-operative Staphylococcus aureus screening and decolonization.

OBJECTIVE: We developed a decision analytic model to evaluate the impact of a preoperative Staphylococcus aureus decolonization bundle on surgical site infections (SSIs), health-care-associated costs (HCACs), and deaths due to SSI. METHODS: Our model population comprised US adults undergoing elective surgery. We evaluated 3 self-administered preoperative strategies: (1) the standard of care (SOC) consisting of 2 disinfectant soap showers; (2) the "test-and-treat" strategy consisting of the decolonization bundle including chlorhexidine gluconate (CHG) soap, CHG mouth rinse, and mupirocin nasal ointment for 5 days) if S. aureus was found at any of 4 screened sites (nasal, throat, axillary, perianal area), otherwise the SOC; and (3) the "treat-all" strategy consisting of the decolonization bundle for all patients, without S. aureus screening. Model parameters were derived primarily from a randomized controlled trial that measured the efficacy of the decolonization bundle for eradicating S. aureus. RESULTS: Under base-case assumptions, the treat-all strategy yielded the fewest SSIs and the lowest HCACs, followed by the test-and-treat strategy. In contrast, the SOC yielded the most SSIs and the highest HCACs. Consequently, relative to the SOC, the average savings per operation was $217 for the treat-all strategy and $123 for the test-and-treat strategy, and the average savings per per SSI prevented was $21,929 for the treat-all strategy and $15,166 for the test-and-treat strategy. All strategies were sensitive to the probability of acquiring an SSI and the increased risk if SSI if the patient was colonized with SA. CONCLUSION: We predict that the treat-all strategy would be the most effective and cost-saving strategy for preventing SSIs. However, because this strategy might select more extensively for mupirocin-resistant S. aureus and cause more medication adverse effects than the test-and-treat approach or the SOC, additional studies are needed to define its comparative benefits and harms.

The Cost-Effectiveness of Preoperative Staphylococcus aureus Screening and Decolonization in Total Joint Arthroplasty.

BACKGROUND: This article presents a break-even analysis for preoperative Staphylococcus aureus colonization screening and decolonization protocols in total hip arthroplasty (THA) and total knee arthroplasty (TKA). METHODS: Protocol costs, baseline infection rates after arthroplasty, and average revision costs were obtained from institutional records and the literature. The break-even analysis determined the absolute risk reduction (ARR) in infection rate required for cost-effectiveness. RESULTS: S aureus nasal screening ($144.07) was cost effective when initial infection rates of TKA (1.10%) and THA (1.63%) had an ARR of 0.56% and 0.45%, respectively. The most inexpensive decolonization treatment ($5.09) was cost effective with an ARR of 0.02% for both TKA and THA. The most expensive decolonization option ($37.67) was cost effective with ARRs of 0.15% (TKA) and 0.12% (THA). CONCLUSION: Preoperative S aureus decolonization can be highly cost effective, whereas colonization screening requires excessively high reductions in infection rate.

Decreased Hospital Costs and Surgical Site Infection Incidence With a Universal Decolonization Protocol in Primary Total Joint Arthroplasty.

BACKGROUND: Staphylococcus aureus colonization has been identified as a key modifiable risk factor in the reduction of surgical site infections (SSI) related to elective total joint arthroplasty (TJA). We investigated the incidence of SSIs and cost-effectiveness of a universal decolonization protocol without screening consisting of nasal mupirocin and chlorhexidine before elective TJA compared to a program in which all subjects were screened for S aureus and selectively treated if positive. METHODS: We reviewed 4186 primary TJAs from March 2011 through July 2015. Patients were divided into 2 cohorts based on the decolonization regimen used. Before May 2013, 1981 TJA patients were treated under a "screen and treat" program while the subsequent 2205 patients were treated under the universal protocol. We excluded the 3 months around the transition to control for treatment bias. Outcomes of interest included SSI and total hospital costs. RESULTS: With a universal decolonization protocol, there was a significant decrease in both the overall SSI rate (5 vs 15 cases; 0.2% vs 0.8%; P = .013) and SSIs caused by S aureus organisms (2 vs 10; 0.09% vs 0.5%; P = .01). A cost analysis accounting for the cost to administer the universal regimen demonstrated an actual savings of $717,205.59. TJA complicated by SSI costs 4.6× more to treat than that of an uncomplicated primary TJA. CONCLUSION: Our universal decolonization paradigm for elective TJA is effective in reducing the overall rate of SSIs and promoting economic gains for the health system related to the downstream savings accrued from limiting future reoperations and hospitalizations.

Impact of active screening for methicillin-resistant Staphylococcus aureus (MRSA) and decolonization on MRSA infections, mortality and medical cost: a quasi-experimental study in surgical intensive care unit.

INTRODUCTION: Methicillin-resistant Staphylococcus aureus (MRSA) is a leading pathogen of healthcare-associated infections in intensive care units (ICUs). Prior studies have shown that decolonization of MRSA carriers is an effective method to reduce MRSA infections in ICU patients. However, there is currently a lack of data on its effect on mortality and medical cost. METHODS: Using a quasi-experimental, interrupted time-series design with re-introduction of intervention, we evaluated the impact of active screening and decolonization on MRSA infections, mortality and medical costs in the surgical ICU of a university hospital in Taiwan. Regression models were used to adjust for effects of confounding variables. RESULTS: MRSA infection rate decreased from 3.58 (baseline) to 0.42‰ (intervention period) (P <0.05), re-surged to 2.21‰ (interruption period) and decreased to 0.18‰ (re-introduction of intervention period) (P <0.05). Patients admitted to the surgical ICU during the intervention periods had a lower in-hospital mortality (13.5% (155 out of 1,147) versus 16.6% (203 out of 1,226), P = 0.038). After adjusting for effects of confounding variables, the active screening and decolonization program was independently associated with a decrease in in-hospital MRSA infections (adjusted odds ratio: 0.3; 95% CI: 0.1 to 0.8) and 90-day mortality (adjusted hazard ratio: 0.8; 95% CI: 0.7 to 0.99). Cost analysis showed that $22 medical costs can be saved for every $1 spent on the intervention. CONCLUSIONS: Active screening for MRSA and decolonization in ICU settings is associated with a decrease in MRSA infections, mortality and medical cost.

Prevention of gram-positive infections in peritoneal dialysis patients in Hong Kong: a cost-effectiveness analysis.

BACKGROUND: Gram-positive bacteria are the major causative pathogens of peritonitis and exit site infection in patients undergoing peritoneal dialysis (PD). We investigated the cost-effectiveness of regular application of mupirocin at the exit site in PD recipients from the perspective of health care providers in Hong Kong. METHODS: A decision tree was designed to simulate outcomes of incident PD patients with and without regular application of mupirocin over a 1-year period. Outcome measures included total direct medical costs, quality-adjusted life-years (QALYs) gained, and gram-positive infection-related mortality rate. Model inputs were derived from the literature. Sensitivity analyses evaluated the impact of uncertainty in all model variables. RESULTS: In a base case analysis, the mupirocin group had a higher expected QALY value (0.6496 vs 0.6456), a lower infection-related mortality rate (0.18% vs 1.64%), and a lower total cost per patient (US $258 vs $1661) compared with the control group. The rate of gram-positive peritonitis without mupirocin and the risk of gram-positive peritonitis with mupirocin were influential factors. In 10,000 Monte Carlo simulations, the mupirocin group had significantly lower associated costs, higher QALYs, and a lower mortality rate 99.9% of the time. CONCLUSIONS: Topical mupirocin appears to be a cost-effective preventive measure against gram-positive infection in incident patients undergoing PD. The cost-effectiveness of mupirocin is affected by the level of infection risk reduction and subject to resistance against mupirocin.

A practical guide to community-acquired MRSA.

As the number of CA-MRSA skin and soft tissue infections continues to grow, it's important to know which patients are at greatest risk and which evidence-based treatment protocols to turn to when needed.

Surgical site infection prevention initiative - patient attitude and compliance.

BACKGROUND: Although the effect of Staphylococcus aureus (SA) decolonization on surgical site infection (SSI) rates has been studied, patient tolerance and acceptance of these regimens has not been assessed. Surgical patients at our hospital's Pre-Admission Testing Clinic (PAT) receive SA reduction protocols instructing the preoperative use of chlorhexidine gluconate (CHG) soap and intranasal mupirocin ointment (MO). Certain insurers do not cover MO costs resulting in out of pocket (OOP) expenses for some patients. OBJECTIVE: This study assessed patient attitudes and compliance with our hospital's SA decolonization regimen. METHODS: One-hundred-forty-six patients received surveys. Descriptive statistics were used for analysis. RESULTS: Of respondents fitting inclusion criteria, 81% followed the MO protocol (MO users) while 89% followed the CHG protocol (CHG users). Fifty-four percent of MO users reported OOP expenses and 13% reported a hard or very hard financial burden. Ninety-three percent of CHG users reported the protocol was easy or very easy to follow. CONCLUSION: Eighty-one percent of patients receiving the SA protocol were fully compliant despite cost or difficulty obtaining MO. Given these barriers and some difficulty with CHG application, we hypothesize compliance may be improved if MO is provided to patients without OOP expenses and if the CHG application method is simplified.

Treatment of paediatric burns with a nanocrystalline silver dressing compared with standard wound care in a burns unit: a cost analysis.

Burns are a leading cause of non-natural death in South African infants and children. Conventional care of partial-thickness burns often requires painful, time consuming and costly twice-daily dressing changes to clean the wound and apply antimicrobial topical agents. A new topical nanocrystalline silver-coated NS dressing (Acticoat; Smith & Nephew) has been developed and is the first-line treatment of choice in many burn centres. However, because of its cost the Department of Health has been reluctant to introduce it as a standard of care. We retrospectively studied 4 randomly selected paediatric burn patients, calculating the cost associated with the use of NS dressings and comparing this with the projected costs of three previously standard burn wound treatment regimens. NS dressings were changed every 3 days based on their sustained and slow release of silver ions over 72 hours. Using NS clearly saved costs compared with the three other regimens. The demonstrated cost savings resulted primarily from the decreased number of dressings, and the presumed shorter hospital stay.

Clinical and cost ineffectiveness of preoperative screening for methicillin-resistant Staphylococcus aureus and intranasal mupirocin in preventing methicillin-resistant S aureus infections in cardiothoracic surgery.

In our recent experience with methicillin-resistant Staphylococcus aureus (MRSA) infections in 488 patients undergoing thoracic cardiovascular surgery, we found only 2 MRSA infections (one sternal and one graft site). Both patients received preoperative bacitracin and had a negative nares culture for MRSA before the initiation of bacitracin therapy. We conclude that preoperative MRSA screening cultures and bacitracin prophylaxis are neither clinically efficacious nor cost-effective in predicting or preventing MRSA in patients undergoing thoracic cardiovascular surgery.

An intranasal irritation assessment of antibacterial ointment alone or in combination with mupirocin versus Bactroban Nasal in rabbits.

The purpose of this study was to evaluate the potential irritating effects and the systemic exposure level of an antibacterial ointment containing REP8839 as a single agent or in combination with mupirocin versus Bactroban Nasal in rabbits. Additionally, the reversibility of REP8839 effects during a 14-day recovery period was assessed. Five treatment groups of six male and six female New Zealand White rabbits received dose levels of 1%, 2%, and 4% REP8839, 2% Bactroban Nasal, or 2% REP8839/2% mupirocin combination. One additional group of six animals/sex served as the control and received the vehicle, Petrolatum/Softisan 649. The test article or vehicle was administered to all groups via topical administration to the external nares, twice a day (approx. 8h intervals between the doses) for 21 consecutive days, at a dose volume of 100 microL per nare/dose for a total of 400 microL per day (200 microL per nare). Two animals/sex/group were maintained for a 14-day recovery period. The external nares were reflected back and the mucosal lining was evaluated and scored for erythema and edema within 30-60 min following the first dose each day. Blood samples were collected from all animals at designated time points on Day 21 of the study to assess systemic exposure levels. Cross-sectioning of the nasal tract was conducted in all the groups for microscopic evaluation. Mucosal scoring of the nares did not reveal any edema or erythema in any of the dose groups with the antibacterial alone, with the combination product, or with Bactroban Nasal. Mean body weights and food consumption were not adversely impacted by the test articles. Minimal plasma exposure was observed in the rabbits (<5 ng/mL). The REP8839 groups did appear to have dose-responsive exposure (from below the limit of quantitation to 5 ng/mL with 1%, 2%, and 4% REP8839, respectively). Microscopic changes on the nasal sectioning noted in these animals were infrequent and considered incidental findings unrelated to administration of the test articles. In conclusion doses of up to 4% of REP8839 ointment as a single agent or 2% in the combination product, as well as 2% Bactroban Nasal, were not found to induce mucosal irritation when applied topically to the external nares twice a day for 21 consecutive days. Additionally, no delayed effects were observed in the recovery animals.

A preoperative decolonization protocol for staphylococcus aureus prevents orthopaedic infections.

UNLABELLED: Staphylococcus aureus (S. aureus) is an independent risk factor for orthopaedic surgical site infection (SSI). To determine whether a preoperative decolonization protocol reduces S. aureus SSIs, we conducted a prospective observational study of patients undergoing elective total joint arthroplasty (TJA) at our institution, with two control groups. The concurrent control group comprised patients of surgeons who did not participate in the intervention study. The preintervention control group comprised patients of participating surgeons who had undergone elective TJA during the year before the study. Patients in the intervention group were screened preoperatively for S. aureus by nasal swab cultures. S. aureus carriers were decolonized with mupirocin ointment to the nares twice daily and chlorhexidine bath once daily for 5 days before surgery. All 164 of 636 participants (26%) who tested positive completed the decolonization protocol without adverse events and had no postoperative S. aureus SSIs at 1-year followup. In contrast, 1330 concurrent control patients had 12 S. aureus infections. If these infections had occurred in the 26% of patients expected to be nasal carriers of S. aureus at a given time, the infection rate would have been 3.5% (12 of 345) in the control group. In addition, the overall infection rate of the participating surgeons, including nonstaphylococcal infections, decreased from 2.6% during the preintervention period to 1.5% during the intervention period, translating to an adjusted economic gain of $231,741 for the hospital. The data suggest a preoperative decolonization protocol reduces S. aureus SSIs in patients undergoing TJA. LEVEL OF EVIDENCE: Level II, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.

Staphylococcus aureus nasal decolonization in joint replacement surgery reduces infection.

UNLABELLED: Surgical site infections (SSIs) with Staphylococcus aureus are a recognized adverse event of hip and knee replacements. We evaluated the impact of a program to detect S. aureus nasal carriers before surgery with preoperative decolonization (using mupirocin twice daily for 5 days prior to surgery) of carriers. Nasal swab samples were obtained from patients prior to surgery from 8/1/2003 through 2/28/2005. Samples were tested using real-time PCR technology to detect S. aureus. The group that developed S. aureus SSI was compared to a combined concurrent and historical control for one year following the operation. S. aureus caused 71% of SSIs in the combined control groups. Of the 1495 surgical candidates evaluated, 912 (61.0%) were screened for S. aureus; 223 of those screened (24.5%) were positive and then decolonized with mupirocin. Among the 223 positive and decolonized patients, three (1.3%) developed a SSI. Among the 689 screen-negative patients, four (0.6%) developed SSIs for an overall rate of 0.77%. Among the 583 control patients who were not screened or decolonized, 10 (1.7%) developed S. aureus SSIs. SSIs from other organisms were 0.44% and 0.69%, respectively. LEVEL OF EVIDENCE: Level III, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.

Preoperative use of mupirocin for the prevention of healthcare-associated Staphylococcus aureus infections: a cost-effectiveness analysis.

OBJECTIVE: Staphylococcus aureus is the most common cause of healthcare-associated infections. Intranasal mupirocin treatment probably decreases S. aureus infections among colonized surgical patients. Using cost-effectiveness analysis, we evaluated the cost-effectiveness of preoperative use of mupirocin for the prevention of healthcare-associated S. aureus infections. METHODS: Three strategies were compared: (1) screen with nasal culture and give treatment to carriers, (2) give treatment to all patients without screening, and (3) neither screen nor treat. A societal perspective was taken. Adverse outcomes included bloodstream infection, pneumonia, surgical site infection, death due to underlying illness or infection, readmission, and the need for home health care. Data inputs were obtained from an extensive MEDLINE review and from publicly available government data sources. The following base-case data inputs (and ranges) for sensitivity analysis were used: rate of S. aureus carriage, 23.1% (19%-55%); efficacy of mupirocin treatment, 51% (8%-75%); mupirocin treatment cost, 48.36 US Dollars (24.18-57.74 US Dollars); and hospital costs of bloodstream infection, 25,128 US Dollars (6,194-40,211 US Dollars), pneumonia, 18,366 US Dollars (5,574-28,952 US Dollars), and surgical site infection 16,256 US Dollars (5,119-22,553 US Dollars). Widespread use of mupirocin has been associated with high levels of mupirocin resistance; therefore, a broad range of estimates for efficacy was tested in the sensitivity analysis. PATIENTS: The target population included patients undergoing nonemergent surgery requiring postoperative hospitalization. RESULTS: Both the screen-and-treat and treat-all strategies were cost saving, saving 102 US Dollars per patient screened and 88 US Dollars per patient treated, respectively. In 1-way sensitivity analyses, the model was robust with respect to all data inputs except for the efficacy of mupirocin treatment. If the efficacy is less than 16.1%, then the screen-and-treat strategy is cost incurring. A treat-all strategy was more cost saving if the rate of S. aureus carriage was greater than 42.7%, the mupirocin cost was less than 29.87 US Dollars, or nursing compensation was greater than 64.21 US Dollars per hour. CONCLUSION: Administration of mupirocin before surgery is cost saving, primarily because healthcare-associated infections are very expensive. The level of mupirocin efficacy is critical to the cost-effectiveness of this intervention.

Randomized, controlled trial of topical exit-site application of honey (Medihoney) versus mupirocin for the prevention of catheter-associated infections in hemodialysis patients.

The clinical usefulness of hemodialysis catheters is limited by increased infectious morbidity and mortality. Topical antiseptic agents, such as mupirocin, are effective at reducing this risk but have been reported to select for antibiotic-resistant strains. The aim of the present study was to determine the efficacy and the safety of exit-site application of a standardized antibacterial honey versus mupirocin in preventing catheter-associated infections. A randomized, controlled trial was performed comparing the effect of thrice-weekly exit-site application of Medihoney versus mupirocin on infection rates in patients who were receiving hemodialysis via tunneled, cuffed central venous catheters. A total of 101 patients were enrolled. The incidences of catheter-associated bacteremias in honey-treated (n = 51) and mupirocin-treated (n = 50) patients were comparable (0.97 versus 0.85 episodes per 1000 catheter-days, respectively; NS). On Cox proportional hazards model analysis, the use of honey was not significantly associated with bacteremia-free survival (unadjusted hazard ratio, 0.94; 95% confidence interval, 0.27 to 3.24; P = 0.92). No exit-site infections occurred. During the study period, 2% of staphylococcal isolates within the hospital were mupirocin resistant. Thrice-weekly application of standardized antibacterial honey to hemodialysis catheter exit sites was safe, cheap, and effective and resulted in a comparable rate of catheter-associated infection to that obtained with mupirocin (although the study was not adequately powered to assess therapeutic equivalence). The effectiveness of honey against antibiotic-resistant microorganisms and its low likelihood of selecting for further resistant strains suggest that this agent may represent a satisfactory alternative means of chemoprophylaxis in patients with central venous catheters.

Process improvement plan for the reduction of sternal surgical site infections among patients undergoing coronary artery bypass graft surgery.

In an attempt to reduce sternal infections caused by Staphylococcus aureus, a protocol was introduced that included the administration of intranasal mupirocin calcium 2% before surgery to patients undergoing cardiothoracic surgery. Surveillance data indicated a 55% reduction in the rate of deep sternal wound infections caused by S aureus and superficial sternal wound infections have declined from 25 to 6 since the adoption of the protocol. At the study institution, this protocol is now an ongoing process to reduce the incidence of sternal infections caused by S aureus among cardiothoracic patients.

A randomized controlled trial of topical exit site mupirocin application in patients with tunnelled, cuffed haemodialysis catheters.

BACKGROUND: Central venous catheters are frequently needed for the provision of haemodialysis, but their clinical usefulness is severely limited by infectious complications. The risk of such infections can be reduced by topical application of mupirocin to the exit sites of non-cuffed catheters or by the use of tunnelled, cuffed catheters. Whether mupirocin offers any additional protection against infection in patients with tunnelled, cuffed haemodialysis catheters has not been studied. METHODS: An open-label, randomized controlled trial was performed comparing the effect of thrice-weekly exit site application of mupirocin (mupirocin group) vs no ointment (control group) on infection rates and catheter survival in patients receiving haemodialysis via a newly inserted, tunnelled, cuffed central venous catheter. All patients were followed until catheter removal and were monitored for the development of exit site infections and catheter-associated bacteraemias. RESULTS: Fifty patients were enrolled in the study. Both the mupirocin (n=27) and control (n=23) groups were similar at baseline with respect to demographic characteristics, comorbid illnesses and causes of renal failure. Compared with controls, mupirocin-treated patients experienced significantly fewer catheter-related bacteraemias (7 vs 35%, P<0.01) and a longer time to first bacteraemia (log rank score 8.68, P<0.01). The beneficial effect of mupirocin was entirely attributable to a reduction in staphylococcal infection (log rank 10.69, P=0.001) and was still observed when only patients without prior nasal Staphylococcus aureus carriage were included in the analysis (log rank score 6.33, P=0.01). Median catheter survival was also significantly longer in the mupirocin group (108 vs 31 days, log rank score 5.9, P<0.05). Mupirocin use was not associated with any adverse patient effects or the induction of antimicrobial resistance. CONCLUSIONS: Thrice-weekly application of mupirocin to tunnelled, cuffed haemodialysis catheter exit sites is associated with a marked reduction in line-related sepsis and a prolongation of catheter survival.

Reduction in gram-positive pneumonia and antibiotic consumption following the use of a SDD protocol including nasal and oral mupirocin.

The objective of this prospective, randomized, double-blind study was to evaluate the effect of the addition of mupirocin to the 'classical' topical SDD regimen (tobramycin 80 mg, polymyxin E 100 mg, amphotericin B 500 mg) on the development of ICU-acquired infections due to gram-positive bacteria. The study was carried out in an intensive care unit (ICU) of a 1400-bed community hospital. All patients admitted to the ICU during a 16-month period, who were expected to require mechanical ventilation for more than 24 hours, were randomized to receive either the 'classical' SDD regimen (Group A) or a modified regimen with mupirocin (Group B). Data from 223 patients requiring mechanical ventilation for at least 48 hours, who were neither infected nor receiving antibiotics on ICU admission, was analysed. A 2% paste containing tobramycin, polymyxin E and amphotericin B was applied every 6 hours in the oropharynx to the patients in Group A, while in Group B this formula was modified with the addition of 2% mupirocin. In Group B 0.2 ml of a 2% mupirocin ointment was also applied four times daily in both nostrils. Patients in Group A received a soft paraffin ointment as a placebo indistinguishable from mupirocin. Patients in both groups received the classic SDD regimen through the nasogastric tube. Systemic antibiotic prophylaxis was not used. Data on lower airway infection, and blood infection, infections of intravascular catheters, antibiotic consumption and expenditures for antibiotics were analysed. The diagnosis of ventilator-associated pneumonia (VAP) was based on quantitative cultures of protected specimen brush samples (PSB) or on the results of distal broncho-alveolar lavage (BAL). One hundred and four patients received the 'classical' SDD and 119 the modified regimen. Overall 29 patients, 20 in Group A and nine in Group B (p < 0.02) had a total of 33 cases of pneumonia. There were 23 episodes of pneumonia in Group A and 10 in Group B (p < 0.02). Gram-positive bacteria were isolated from samples in 17 episodes in Group A and six in Group B (p < 0.02). Staphylococcus aureus was isolated in nine cases of pneumonia in Group A and once in the 'mupirocin' group (p < 0.05). MRSA were isolated in seven out of nine cases in Group A and in the only case in Group B. There were no differences in the isolation of gram-negative bacilli. Antibiotic consumption and cost were lower in Group B. In conclusion, our data show that the topical use of a modified formula of SDD, with the addition of mupirocin to the oral paste and in the anterior nares, is associated with a reduction in lung infections caused by gram-positives and in a reduction in antibiotic consumption and in the overall expenditure for antibiotics.

Cost-effectiveness of prophylactic nasal mupirocin in patients undergoing peritoneal dialysis based on a randomized, placebo-controlled trial.

The study objective was to measure the benefits of elimination of nasal carriage of Staphylococcus aureus by calcium mupirocin ointment in patients undergoing continuous ambulatory peritoneal dialysis. The design was a prospective, placebo-controlled, randomized clinical trial. The subjects were 267 patients recruited from nine renal units in Belgium, France and the UK. The main outcome measures were the rate of catheter exit site infection (ESI), rates of other infections and healthcare costs from the perspective of a hospital budget-holder. The rate of ESI caused by S. aureus was significantly reduced from one in 28.1 patient months to one in 99.3 patient months (P = 0.006) and there were also non-significant trends towards lower rates of ESI caused by any organism and peritonitis caused by S. aureus. In comparison with the placebo group, patients in the mupirocin group with ESI had lower antibiotic (P = 0.02) and hospitalization costs (P = 0.065). However, overall costs of antibiotic treatment, for all infections combined, were not significantly different (P = 0.2) and total antibiotic costs (including mupirocin) were significantly higher in the mupirocin group (P = 0.001). Mupirocin prophylaxis would have been cost-neutral if the rate of ESI increased to >75% in the placebo group, or if all healthcare costs increased by 40%, or if the cost of screening was reduced from Pound Sterling 15 to Pound Sterling 3 per patient, or if the cost of mupirocin treatment was reduced from Pound Sterling 93 to Pound Sterling 40 per patient year. In conclusion, savings in healthcare costs are unlikely to be sufficiently great to offset the cost of mupirocin and screening for nasal carriage of S. aureus. The decision about whether or not to implement mupirocin should depend on a local analysis of the value of preventing ESIs caused by S. aureus.