Background
Methods
Results
The development of antimicrobial resistance and the selection of pathogenic bacteria from use of antibiotics
Antimicrobials and resistance
-
enhancing infection prevention and control;
-
prescribing and dispensing antimicrobials when they are truly needed; and
-
prescribing and dispensing the right antimicrobial(s) to treat the illness.
Antibiotics and C. difficile infection
Antibiotics and invasive candidiasis
The global burden of antimicrobial resistance
-
lead to some infections becoming untreatable;
-
lead to inappropriate empirical treatment in critically ill patients where an appropriate and prompt treatment is mandatory;
-
increase length of hospital stay, morbidity, mortality and cost; and
-
make necessary alternative antimicrobials which are more toxic, less effective, or more expensive.
-
to improve awareness and understanding of antimicrobial resistance;
-
to strengthen knowledge through surveillance and research;
-
to reduce the incidence of infection;
-
to optimize the use of antimicrobial agents; and
-
to develop the economic case for sustainable investment that takes account of the needs of all countries, and increase investment in new medicines, diagnostic tools, vaccines and other interventions.
Mechanism of resistance
-
the inactivation or modification of the antibiotic;
-
an alteration or the protection of the target site of the antibiotic that reduces its binding capacity;
-
the modification of metabolic pathways to circumvent the antibiotic effect; and
-
the reduced intracellular antibiotic accumulation by decreasing permeability and/or increasing active efflux of the antibiotic.
Evolution and dissemination of resistance
Antibiotic resistance in Enterobacteriaceae
Antibiotic resistance in Non-fermenting gram-negative bacteria
Antibiotic resistance in Enterococci
Antibiotic resistance in Bacteroides fragilis
Antibiotic resistance in intra-abdominal infections
ESBL-producing Enterobacteriaceae
Klebsiella pneumoniae Carbapenemases
Pseudomonas aeruginosa
Enterococci
Methicillin resistant Staphylococcus aureus (MRSA)
Salmonella typhi
Bacteroides fragilis
Antimicrobial stewardship
Management of intra-abdominal infections
Classifications
-
the origin of source of infection;
-
the anatomical extent of infection;
-
the presumed pathogens involved and risk factors for major resistance patterns; and
-
the patient's clinical condition.
Antimicrobial selection
Published guidelines
Antimicrobial selection
Antimicrobial selection in community-acquired infections
Antimicrobial selection in health-care associated infections
Antibiotic selection in critically Ill patients
-
early source control procedures when indicated;
-
early initiation of therapy (ideally, within 1 h);
-
correct dosing;
-
considering risk factor for MDRO; and
-
avoiding use of identical antibiotic and the same antibiotic class administered in the preceding 3 months.
De-escalation
Antibiotic armamentarium
Antibiotic | Enterococci | Ampicillin-resistant enterococci | Vancomycin-resistant enterococci | Enterobacteriaceae | ESBL-producing Enterobactericeae
|
Pseudomonas aeruginosa
| Anaerobic Gram-negative bacilli |
---|---|---|---|---|---|---|---|
Penicillins/Beta-lactamase Inhibitors | |||||||
Amoxicillin/clavulanate | + | − | − | + | − | − | + |
Ampicillin/Sulbactam | + | − | − | + | − | − | +/− |
Piperacillin/tazobactam | + | − | − | + | +/− | + | + |
Carbapenems | |||||||
Ertapenem | − | − | − | + | + | − | + |
Imipenem/cilastatin | +/−a
| − | − | + | + | + | + |
Meropenem | − | − | − | + | + | + | + |
Doripenem | − | − | − | + | + | + | + |
Fluoroquinolones | |||||||
Ciprofloxacin | − | − | − | + | − | +b
| − |
Levofloxacin | +/− | − | − | + | − | +/− | − |
Moxifloxacin | +/− | − | − | + | − | − | +/− |
Cephalosporins | |||||||
Ceftriaxone | − | − | − | + | − | − | − |
Ceftazidime | − | − | − | + | − | + | − |
Cefepime | − | − | − | + | +/− | + | − |
Ceftolozane/tazobactam | − | − | − | + | + | + | − |
Ceftazidime/avibactam | − | − | − | + | + | + | − |
Aminoglycosides | |||||||
Amikacin |
c
|
c
|
c
| + | + | + | |
Gentamicin |
c
|
c
|
c
| + | + | + | − |
Glycylcyclines | |||||||
Tigecycline | + | + | + | +d
| + | − | + |
5-nitroimidazole | |||||||
Metronidazole | − | − | − | − | − | − | + |
Polymyxin | |||||||
Colistimethate (Colistin) | − | − | − | +e
| + | + | − |
Glycopeptides | |||||||
Teicoplanin | + | + | − | − | − | − | − |
Vancomycin | + | + | − | − | − | − | − |
Oxazolidines | |||||||
Linezolid | + | + | + | − | − | − | − |
Intravenous Antibiotic | Intravenous dosing recommendation for patients with normal renal function*(CrCl > 90 mL/min) |
---|---|
Penicillins/ Beta-lactamase Inhibitors | |
Amoxicillin/clavulanate | 1.2 g 8-hourly |
Ampicillin/Sulbactam | 3 g 6-hourly |
Piperacillin/tazobactam | 4.5 g 6- 8-hourly or 3.375 g 6-hourly |
Carbapenems | |
Ertapenem | 1 g 24-hourly |
Imipenem/cilastatin | 0.5 g 6-hourly (or1 g 8-hourly) |
Meropenem | 1 g 8-hourly |
Fluoroquinolones | |
Ciprofloxacin | 400 mg 8–12 hourly |
Levofloxacin | 750 mg 24-hourly |
Moxifloxacin | 400 mg 24-hourly |
Cephalosporins | |
Ceftriaxone | 1–2 g 24-hourly |
Ceftazidime | 2 g 8-hourly |
Cefepime | 1–2 g 8 hourly |
Ceftolozane/tazobactam | 1.5 g 8-hourly |
Ceftazidime/avibactam | 2.5 g 8-hourly |
Glycylcyclines | |
Tigecycline | 100 mg initial dose, then 50 mg 12-hourly |
Aminoglycosides | |
Amikacin | 15–20 mg/kg 24-hourly |
Gentamicin | 5–7 mg/kg 24-hourly |
5-nitroimidazole | |
Metronidazole | 500 mg 6–8 hourly |
Glycopeptides | |
Teicoplanin | 12 mg/kg 12-hourly times 3 loading dose then 12 mg/kg 24-hourly |
Vancomycin | 15–20 mg/kg/dose 8–12 hourly; in critically ill patients 25–30 mg/kg loading dose |
Oxazolidinonees | |
Linezolid | 600 mg 12 hourly |
Polymyxins | |
Colistin | US: 2.5 to 5 mg/kg CBA 8–12 hourly Europe: 9 million IU 8–12 hourly as a slow intravenous; in critically ill patients 9 million IU loading dose as a slow intravenous infusion |
Beta-lactam/beta-lactamase inhibitor combinations
Cephalosporins
Fluoroquinolones
Carbapenems
Aminoglycosides
Tigecycline
Polymixins
Fosfomycin
New antibiotics
The effect of fungal involvement in IAI
-
recent abdominal surgery;
-
anastomotic leaks;
-
necrotizing pancreatitis; and
-
failure of treatment for bacterial infections.
Dosage
The value of intra-operative specimens
-
to expand antimicrobial regimen if the initial choice is too narrow; and
-
to perform a de-escalation is the empirical regimen is too broad.