Impact of formulary interventions on the minimum inhibitory concentration of methicillin-resistant Staphylococcus aureus to mupirocin, chlorhexidine, and octenidine in a Singapore tertiary institution.

Methicillin-resistant Staphylococcus aureus (MRSA) decolonization is an effective measure to prevent clinical infection but resistance is a concern. We aim to evaluate the impact of mupirocin (MUP) ointment formulary removal, plateauing use of chlorhexidine gluconate (CHG), and hospital-wide introduction of octenidine (OCT)-based products on the minimum inhibitory concentration (MIC) of MRSA to MUP, CHG, and OCT in our hospital. A prevalence study was conducted at three time points (TP) on consecutive MRSA screening isolates to evaluate for their MICs to MUP, CHG, and OCT using broth microdilution sensititre plates and detection of the ileS-2 gene encoding high-level MUP resistance in 2013 (pre-intervention TP1; n = 160), 2016 (early post-intervention TP2; n = 99) and 2017 (late post-intervention TP3; n = 76). Statistical analyses were performed using Chi square test with reference from TP1. There was a significant improvement in MUP susceptibility (MIC < 4 mcg/ml) from 71.9% (TP1) to 86.9% (TP2; p = 0.006) to 88.2% (TP3; p = 0.007). The prevalence of MUP high-level resistance (MIC > 256 mcg/ml) reduced from 25.0% (TP1) to 12.1% (TP2; p = 0.014) to 5.3% (TP3; p = 0.001). Likewise, the prevalence of isolates harboring the ileS-2 gene decreased from 28.1% (TP1) to 18.2% (TP2; p = 0.072) to 9.2% (TP3; p = 0.002). OCT MIC range remains stable at 0.5 to 1 mcg/ml across all three TPs. The proportion of isolates with reduced CHG susceptibility (MIC ≥ 4 mcg/ml) increased over the three TPs from 23.1 to 27.2% (p = 0.45) to 42.1% (p = 0.003). Active formulary regulations have an impact on the resistance profile of MRSA and can be used as a strategy to preserve the MRSA decolonization armamentarium.

The effect of a whole-system approach in an antimicrobial stewardship programme at the Singapore General Hospital.

Inappropriate antibiotic use contributes to antimicrobial resistance. Multi-faceted antimicrobial stewardship programmes (ASPs) are recommended for sustainable changes in prescribing practices. A multi-disciplinary ASP was established in October 2008 and piloted in the Departments of General Surgery, Renal Medicine and Endocrinology sequentially. To improve the quality of patient care via optimising the (1) choice, (2) dose, (3) route and (4) duration of antibiotics, a "whole-system" approach incorporating prospective review with immediate concurrent feedback (ICF), prescriber education (public or individualised), de-escalation of therapy, dose optimisation and parenteral-to-oral conversion, while recognising the autonomy of primary prescribers, was adopted. The audited department received a quarterly outcomes report and any common unaccepted practices would be addressed. Outcomes were analysed for 12 months post-ASP implementation. A total of 1,535 antibiotic prescriptions were reviewed. Antimicrobial use in 376 (24.5%) prescriptions was inappropriate. Of 596 interventions made, 70.2% were accepted. A reduction in audited antibiotics consumption resulted in acquisition cost savings of S$198,575 for the hospital. Patients' cost-savings attributable to ASP-initiated interventions were $91,194. The overall all-cause mortality rate and median monthly inpatient-days pre- and post-intervention remained stable. A "whole-system" ASP was effective in optimising antibiotic use in our hospital, without compromising clinical outcomes.

Utility and safety of procalcitonin in an antimicrobial stewardship program (ASP) in patients with malignancies.

As data on procalcitonin utility in antibiotics discontinuation [under an antimicrobial stewardship program (ASP)] in patients with malignancies are lacking, we aimed to evaluate the utility of procalcitonin in an ASP in patients with malignancies. We conducted a retrospective review of the ASP database of all patients with malignancies in whom at least one procalcitonin level was taken and our ASP had recommended changes in carbapenem regimen, from January to December 2011. We compared clinical outcomes between two groups of patients: patients whose physicians accepted and those whose physicians rejected ASP interventions. There were 749 carbapenem cases reviewed. Ninety-nine were suggested to either de-escalate, discontinue antibiotics, or narrow the spectrum of empiric treatment, based on procalcitonin trends. While there was no statistical difference in the mortality within 30 days post-ASP intervention (accepted: 8/65 patients vs. rejected: 9/34 patients; p = 0.076), the median duration of carbapenem therapy was significantly shorter (5 vs. 7 days; p = 0.002). Procalcitonin use safely facilitates decisions on antibiotics discontinuation and de-escalation in patients with malignancies in the ASP.

Use of procalcitonin (PCT) to guide discontinuation of antibiotic use in an unspecified sepsis is an antimicrobial stewardship program (ASP).

Clinicians have used procalcitonin (PCT) (biomarker to differentiate bacterial from non-bacterial sepsis) to guide use of antibiotics in patients. As the data for utility of PCT to discontinue antibiotics in an antimicrobial stewardship program (ASP) are lacking, we aim to describe the outcomes of patients in whom PCT was used to discontinue antibiotics under our ASP. An antimicrobial stewardship (AS) team intervened to discontinue antibiotics in patients with persistent fever or leucocytosis, source of sepsis unknown or negative bacteriological cultures, who had completed an adequate course of antibiotic therapy and had a PCT of <0.5 µg/L. Main outcomes evaluated were 14-day re-infection, 30-day mortality and readmission. Antibiotic therapy was discontinued in 42 patients in 1 year. Unknown source of sepsis was found in 38% of the patients (including possible malignant fever) and culture-negative pneumonia was found in 21%. Two patients died of advanced cancer. One patient decided for comfort care and died one week later. One patient died due to a second episode of pneumonia 37 days after first PCT test. Six patients were readmitted within 30 days due to non-infectious causes. Three patients were readmitted due to culture-negative pneumonia. None had a 14-day re-infection. PCT used to discontinue antibiotics under our ASP did not compromise patients' outcome.

Review of peripherally inserted central catheters in the Singapore acute-care hospital.

Peripherally inserted central catheters are frequently used whenever reliable central venous access is required for a prolonged period of time. The objective of this study was to review utilisation profile, complication rates and outcomes of patients who were treated in our hospital with the therapy that required placement of the peripherally inserted central catheter. We reviewed the medical records of all patients who had peripherally inserted central catheter placed between the beginning of July and the end of October 2002. Five patients who remained hospitalised at the time of review (six weeks after the last day of study period) were excluded. Seventy-eight patients with 94 peripherally inserted central catheters were analysed in detail. Sixty-four peripherally inserted central catheters (68.1%) were placed for prolonged antibiotic therapy, 27 (28.7%) mainly to administer total parenteral nutrition and 3 (3.2%) were inserted for other reasons. Catheters were in place before removal for a mean 17.2 days. Forty-eight catheters (51.1%) were removed after completion of therapy on average 20.2 days after insertion. Complications were frequent but minor. Thirty-three catheters (35.1%) were removed due to catheter-related complications. The most common complication were phlebitis followed by accidental removal. In summary, peripherally inserted central catheters proved to be reasonably safe and a reliable way of providing therapy requiring prolonged intravenous access. Complications were frequent but relatively minor. Complication rates in our study were similar to those reported in other studies on this subject. Peripherally inserted central catheters remain a convenient and reasonable alternative to other centrally or peripherally inserted venous devices.

Extended-spectrum beta-lactamases in clinical isolates of Escherichia coli and Klebsiella spp. in a Singapore hospital: clinical spectrum.

INTRODUCTION: The rising prevalence of extended-spectrum beta-lactamases in gram-negative bacillary pathogens is an important clinical problem resulting from the extensive use of broad-spectrum antibiotics. The emergence of the extended-spectrum beta-lactamases increases the possibility that traditional, empiric antimicrobial regimens may be ineffective. The aims of this study are: to determine the epidemiologic characteristics and clinical outcome of patients diagnosed with infection caused by Klebsiella spp. and Escherichia coli producing extended-spectrum beta-lactamases; to define a subgroup of patients who may benefit from early, empiric therapy; and to determine the local antibiotic sensitivity pattern in order to improve antibiotic utilisation in our hospital. MATERIALS AND METHODS: A 4-month retrospective review of patients hospitalised in Changi General Hospital between November 2000 and February 2001 who were diagnosed with infection caused by isolates of Klebsiella spp. or Escherichia coli producing extended-spectrum beta-lactamases. RESULTS: During the study period, 44 % of Klebsiella spp. and 16.1 % of Escherichia coli isolates were reported as producers of the extended-spectrum beta-lactamases. Sixty-eight patients were assessed to have clinically significant infection caused by 75 isolates. Most of them were elderly, had multiple medical problems and were recently treated with beta-lactam antibiotics. There was a trend toward better outcome in patients who received adequate initial, empiric therapy. CONCLUSION: Patients with infections caused by extended-spectrum beta-lactamase producing Enterobacteriaceae have certain identifiable, common clinical characteristics. In our institution, only carbapenems remain effective against all isolates of Klebsiella spp. or Escherichia coli producing extended-spectrum beta-lactamases. Further research is necessary to define a group of patients who can benefit from an early, broad-spectrum, empiric therapy.

Burkholderia pseudomallei meningitis following inadequate treatment of melioidotic mycotic aneurysm.

We report a 64-year-old man presenting with meningitis caused by Burkholderia pseudomallei predisposed by persistent aortic graft infection following inadequate treatment of a melioidotic mycotic aneurysm. The relapse of melioidosis presenting as acute meningitis is a unique event. Successful treatment of deep-seated melioidosis can only be achieved when robust antimicrobial therapy is combined with appropriate surgical debridement.

Control of a hospital-wide vancomycin-resistant Enterococci outbreak.

BACKGROUND: To analyze control measures used to eradicate a large vancomycin-resistant Enterococci (VRE) outbreak in a nonendemic 1600-bed tertiary care institution. METHODS: In mid-March 2005, VRE Van B was isolated from 2 clinical samples from different wards. Despite such measures as screening patients sharing rooms with index cases and isolating VRE patients, 43 isolates from different wards were detected by the end of March 2005. To eradicate a hospital-wide outbreak, a coordinated strategy between March and June 2005 comprised (1) formation of a VRE task force, (2) hospital-wide screening, (3) isolation of carriers, (4) physical segregation of contacts, (5) surveillance of high-risk groups, (6) increased cleaning, (7) electronic tagging of VRE status, and (8) education and audits. This is a retrospective study of this multipronged approach to containing VRE. The adequacy of rectal swab sampling for VRE was assessed in a substudy of 111 patients. The prevalence of methicillin-resistant Staphylococcus aureus (MRSA)/VRE co-colonization or co-infection also was determined. RESULTS: A total of 19,574 contacts were identified. Between April and June 2005, 5095 patients were screened, yielding 104 VRE carriers, 54 of whom (52%) were detected in the first 2 weeks of hospital-wide screening. The initial positive yield of 11.4% of persons actively screened declined to 4.2% by the end of June 2005. Pulsed-field typing revealed 1 major clone and several minor clones among the 151 total VRE cases, including 4 clinical cases. Hospital-wide physical segregation of contacts from other patients was difficult to achieve in communal wards. Co-colonization or co-infection with MRSA, which was present in 52 of 151 cases (34%) and the indefinite electronic tagging of positive VRE status strained limited isolation beds. Analysis of 2 fecal or rectal specimens collected 1 day apart may detect at least 83% of VRE carriers. CONCLUSION: A multipronged strategy orchestrated by a central task force curbed but could not eradicate VRE. Control measures were confounded by hospital infrastructure and high MRSA endemicity.

Reducing antimicrobial resistance through appropriate antibiotic usage in Singapore.

Two alarming trends threaten the future utility of antimicrobial agents: rise of antimicrobial resistance and decline in development of new antibiotics. The continuing emergence and spread of antimicrobial-resistant microbes--a global public health issue--exacerbates the problem of paucity of new antimicrobial agents. Singapore's public sector hospitals currently have some of the highest rates of antimicrobial resistance worldwide, evolving with surprising speed over the past two decades. Because there was no systematic surveillance until fairly recently, this healthcare problem has not been emphasised. In contrast, it is difficult to assess the scale of antimicrobial resistance in the community in view of the lack of recent research, although indirect evidence suggests that this is also a source of concern. A panel comprising representatives from multiple professional healthcare societies was convened to address the issue of antimicrobial resistance in Singapore, focusing on the conservation of antibiotics against resistance. From a review of the medical literature, potentially successful strategies involve facilitating prudent and appropriate use of antimicrobial agents in tandem with other interventions in infection control. Presently, there is a lack of data on the appropriate use of antibiotics in Singapore. The recommendations of the panel are: The professions should look into ways and means to support systematic data collection on antibiotic use and appropriateness of use; The Ministry of Health should take a more active and positive role in regulating antibiotic usage; Hospitals should actively support effective antimicrobial stewardship programmes; Educators should coordinate programmes to give greater emphasis on appropriate antimicrobial prescription, and support good clinical practice; and, Local and regional branches of pharmaceutical companies should adopt the Pharmaceutical Research and Manufacturers of America's updated code of conduct on interactions with physicians as a step towards re-aligning the industry-physician relationship in the direction of educational and informational support.