الفهرس 
Antimicrobial Drugs Used in ICUOnly 14 pages are availabe for public view
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Abstract
Resistance is a measure of decreased ability of an antimicrobial agent to kill or inhibit the growth of a microbial organism. In practice, this is determined by testing a patient isolate against an antimicrobial in an invitro assay system. In a patient exposed to an antimicrobial agent, resistant organisms can emerge by selection for and expansion of subpopulations of spontaneously generated, less susceptible mutants of antimicrobial target.
The epidemiology of resistance is extremely local. Most outbreaks and clusters involve a few patients in a unit, and the prevalence of resistance is often highest in those units where the most vulnerable patients are congregated and where antibacterial use consequently is heaviest. Successful epidemic strains are critical to the accumulation of many resistances. Common vectors in hospitals are contact with staff members and contact with non-sterile devices, or procedures. Spread in the community is favored by those factors that have aided epidemics throughout history; that is, crowding and travel. Many strains, resistant or otherwise, spread locally, but a few achieve a much wider distribution.
The previous use of antimicrobial agents has been identified as an important factor in the emergence of antibiotic resistant bacterial infections in the ICU. Non clinical use of antibiotic. and inhibition of the normal intestinal flora are other contributing factors to the development of resistance. In addition, inappropriate dosing and/or duration of antibiotics as well as increased antibiotic usage contribute directly to the increased prevalence of resistance.
Bacteria may use or combine multiple mechanisms against a single agent or class of agents or a single change may result in development of resistance to several different agents. General mechanisms of resistance to antimicrobial agent are diminished intracellular drug concentration, increased efflux of the agent, decreased outer membrane permeability, decreased cytoplasmic membrane transport, reversible or irreversible drug inactivation, target modification, and target bypass. Inactivating enzymes remain the predominant mechanism of resistance to several major classes of antimicrobial agents.
Many investigators explored the role of biomarkers in diagnosing infection, starting antibiotics, modifying the dose and terminating the treatment. Many studies tried to correlate different biomarker levels and prognosis of infection.
Major efforts are needed to slow down the rising problem of multidrug resistance. The Centers for Disease Control recommend four strategies for health care settings: prevent infections, diagnose and treat infections, prudent and rational use of antimicrobials, and prevent transmission. Strategies for prevention of nosocomial infections are hand hygiene practices; prevention of central venous catheter-related blood stream infections as well as urinary tract catheters; judicious use of antimicrobials for therapy and prophylaxis; enhancement of host defences; skin care; and early enteral feeding with human milk. All patients harboring MDR organisms should be placed in contact isolation, either in single rooms or cohorted with other colonized/infected patients.
The Antimicrobial Stewardship Program (ASP) is a team work specific for each hospital. It entails the co-operation of clinicians, pharmacists, laboratory specialists and nursing staff.The ASP works to ensure the optimal selection, dose, and duration of antimicrobials that lead to the best clinical outcome for the treatment or prevention of infection while producing the fewest possible side effects and the lowest risk for subsequent resistance.
Treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections is a true challenge: The availability of newer anti-staphylococcal agents has improved but has also complicated the choices for treating MRSA infections in the ICU. Factors to consider include site and severity of infection, the minimum inhibitory concentration (MIC) to vancomycin, and co-morbidities. For bacteraemia and endovascular infections including endocarditis for which bactericidal therapy is preferred, vancomycin and daptomycin are both appropriate alternatives. Vancomycin and linezolid are both listed as options for MRSA in the American Thoracic Society and Infectious Diseases Society of America guidelines for hospital-acquired pneumonia (HAP). Routine use of combination therapy is not recommended for MRSA endocarditis except for prosthetic valve disease.
There are no data from randomized controlled clinical trials comparing antibiotic treatments for ESBL-producing Enterobacteriaceae. Carbapenems have been considered the treatment of choice, because they are not hydrolyzed by ESBLs, are highly active invitro, and high rates of successful outcomes have been reported. The use of any third- and fourth-generation cephalosporin for the treatment of serious infections due to ESBL-producing Enterobacteriaceae had not been recommended because of high failure rates for infections caused by strains with minimum inhibitory concentration (MIC) values of 2 to 8 mg/mL. For ESBL-producing Entero-bacteriaceae treated with third and fourth-generation cephalosporins where MICs are 1 or less, failure rates are much lower.
Most isolates of MDR P.aeruginosa and Acinetobacter spp. are susceptible to polymyxins, and a combination of colistin and polymyxin B are frequently used for these infections. Aminoglycosides have also been used for P aeruginosa and Acinetobacter spp, when they are susceptible. Inhaled nebulized antibiotics, usually tobramycin or colistin, can be considered as an adjunctive treatment for severe drug-resistant P aeruginosa and Acinetobacter spp. pneumonia, in combination with systemic antimicrobials.