Quantifying the Economic and Clinical Value of Reducing Antimicrobial Resistance in Gram-negative Pathogens Causing Hospital-Acquired Infections in Australia.

INTRODUCTION: Antimicrobial resistance (AMR) is a global public health challenge requiring a global response to which Australia has issued a National Antimicrobial Resistance Strategy. The necessity for continued-development of new effective antimicrobials is required to tackle this immediate health threat is clear, but current market conditions may undervalue antimicrobials. We aimed to estimate the health-economic benefits of reducing AMR levels for drug-resistant gram-negative pathogens in Australia, to inform health policy decision-making. METHODS: A published and validated-dynamic health economic model was adapted to the Australian setting. Over a 10-year time horizon, the model estimates the clinical and economic outcomes associated with reducing current AMR levels, by up to 95%, of three gram-negative pathogens in three hospital-acquired infections, from the perspective of healthcare payers. A willingness-to-pay threshold of AUD$15,000-$45,000 per quality-adjusted life-year (QALY) gained and a 5% discount rate (for costs and benefits) were applied. RESULTS: Over ten years, reducing AMR for gram-negative pathogens in Australia is associated with up to 10,251 life-years and 8924 QALYs gained, 9041 bed-days saved and 6644 defined-daily doses of antibiotics avoided. The resulting savings are estimated to be $10.5 million in hospitalisation costs, and the monetary benefit at up to $412.1 million. DISCUSSION: Our results demonstrate the clinical and economic value of reducing AMR impact in Australia. Of note, since our analysis only considered a limited number of pathogens in the hospital setting only and for a limited number of infection types, the benefits of counteracting AMR are likely to extend well beyond the ones demonstrated here. CONCLUSION: These estimates demonstrate the consequences of failure to combat AMR in the Australian context. The benefits in mortality and health system costs justify consideration of innovative reimbursement schemes to encourage the development and commercialisation of new effective antimicrobials.

Antimicrobial susceptibility of gram-negative pathogens isolated from patients with complicated intra-abdominal infections in South African hospitals (SMART Study 2004-2009): impact of the new carbapenem breakpoints.

BACKGROUND: The Study for Monitoring Antimicrobial Resistance Trends (SMART) follows trends in resistance among aerobic and facultative anaerobic gram-negative bacilli (GNB) isolated from complicated intra-abdominal infections (cIAIs) in patients around the world. METHODS: During 2004-2009, three centralized clinical microbiology laboratories serving 59 private hospitals in three large South African cities collected 1,218 GNB from complicated intra-abdominal infections (cIAIs) and tested them for susceptibility to 12 antibiotics according to the 2011 Clinical Laboratory Standards Institute (CLSI) guidelines. RESULTS: Enterobacteriaceae comprised 83.7% of the isolates. Escherichia coli was the species isolated most commonly (46.4%), and 7.6% of these were extended-spectrum ß-lactamase (ESBL)-positive. The highest ESBL rate was documented for Klebsiella pneumoniae (41.2%). Overall, ertapenem was the antibiotic most active against susceptible species for which it has breakpoints (94.6%) followed by amikacin (91.9%), piperacillin-tazobactam (89.3%), and imipenem-cilastatin (87.1%), whereas rates of resistance to ceftriaxone, cefotaxime, ciprofloxacin, and levofloxacin were documented to be 29.7%, 28.7%, 22.5%, and 21.1%, respectively. Multi-drug resistance (MDR), defined as resistance to three or more antibiotic classes, was significantly more common in K. pneumoniae (27.9%) than in E. coli (4.9%; p<0.0001) or Proteus mirabilis (4.1%; p<0.05). Applying the new CLSI breakpoints for carbapenems, susceptibility to ertapenem was reduced significantly in ESBL-positive E. coli compared with ESBL-negative isolates (91% vs. 98%; p<0.05), but this did not apply to imipenem-cilastatin (95% vs. 99%; p=0.0928). A large disparity between imipenem-cilastatin and ertapenem susceptibility in P. mirabilis and Morganella morganii was documented (24% vs. 96% and 15% vs. 92%, respectively), as most isolates of these two species had imipenem-cilastatin minimum inhibitory concentrations in the 2-4 mcg/mL range, which is no longer regarded as susceptible. CONCLUSIONS: This study documented substantial resistance to standard antimicrobial therapy among GNB commonly isolated from cIAIs in South Africa. With the application of the new CLSI carbapenem breakpoints, discrepancies were noted between ertapenem and imipenem-cilastatin with regard to the changes in their individual susceptibilities. Longitudinal surveillance of susceptibility patterns is useful to guide recommendations for empiric antibiotic use in cIAIs.

Therapeutic applications of tigecycline in the management of complicated skin and skin structure infections.

Complicated skin and skin structure infections encompass a diverse range of diseases frequently caused by Gram-positive pathogens, and most commonly by Staphylococcus aureus and Streptococcus pyogenes. Treatment of these infections represents a growing clinical challenge as increases in multi-drug-resistant organisms and cross-resistance to antimicrobial therapy have made empiric therapeutic choices more difficult, particularly for patients with known risk factors or who are immunocompromised. Complicating this issue has been the relative lack of new agents with antimicrobial potency against prevalent resistant species such as meticillin resistant S. aureus (MRSA). Tigecycline, a novel glycylcycline, is a broad-spectrum antibiotic with potent microbiological activity against the wide variety of organisms implicated in the aetiology of complicated skin and skin structure infections. Recent phase III clinical data confirm previous observations on the safety and efficacy of tigecycline for the treatment of complicated skin and skin structure infections. Tigecycline was shown to be non-inferior to combination vancomycin-aztreonam regimens and exhibited high clinical success rates. MIC(90) values for tigecycline were uniformly low for both susceptible and resistant pathogens. Adverse events were similar in incidence for both patient populations, with nausea and vomiting reported more frequently with tigecycline treated patients while rash and elevated liver transaminases were most commonly observed in the vancomycin-aztreonam treatment group. Tigecycline helps to address the urgent need for new antimicrobial agents to combat the emergence of multi-drug-resistant Gram-positive pathogens. Current clinical, microbiological and safety data support the use of tigecycline as a valuable therapeutic option in the treatment of complicated skin and skin structure infections.

Guideline for the management of nosocomial infections in South Africa.

OBJECTIVE: To write a guideline for the management and prevention of nosocomial infections in South Africa in view of the following: Nosocomial infections are a common and increasing problem globally, including South Africa. Widely varying standards of prevention and management of these important infections. Increasing and emerging antimicrobial resistance among commonly isolated pathogens. The significant economic burden of these infections on the health care system as well as their impact on patient morbidity and mortality. The main aims of the guideline are to provide recommendations for the initial choice of antimicrobial agents and the appropriate management of these infections encompassing the following conditions: (i) nosocomial pneumonia, health care-associated pneumonia and ventilator-associated pneumonia; (ii) nosocomial bloodstream infections; (iii) nosocomial intravascular infections; (iv) nosocomial urinary tract infections; (v) nosocomial intra-abdominal infections; and (vi) nosocomial surgical skin and soft-tissue infections. EVIDENCE: Working group of clinicians from relevant disciplines, following detailed literature review. RECOMMENDATIONS: These include details of the likely pathogens, an appropriate diagnostic approach, antibiotic treatment options and appropriate preventive strategies. ENDORSEMENT: The guideline document was endorsed by the South African Thoracic Society, the Critical Care Society of Southern Africa and the Federation of Infectious Diseases Societies of Southern Africa.