OTHER PROBLEMS WITH RESISTANCE
Vancomycin has been the drug used to treat serious MRSA infections. However, intermediate-level vancomycin resistance has emerged among staphylococci as well as rare cases of fully resistant strains. New anti-MRSA agents have been introduced—linezolid, daptomycin, tigecycline, and quinupristindalfopristin— and are most welcome.
In addition to S aureus, other gram-positive bacteria have become multidrug-resistant. A dramatic increase in vancomycin-resistant enterococci (VRE) has been seen among hospitalized patients. Enterococci are inhabitants of the GI tract that act as opportunistic pathogens, causing surgical-site infections, UTIs, and bacteremia. Most VRE are Enterococcus faecium. Testing of isolates from 76 medical centers in the United States showed vancomycin resistance among E faecium to vary from 45% in the New England states to 85% in the east south-central states.32 VRE has intrinsic resistance to multiple antimicrobial drugs, making therapy difficult; fortunately, the newer agents—tigecycline, linezolid, and quinupristin-dalfopristin—have antibacterial activity against vancomycin-resistant E faecium.
Nosocomial infections caused by multidrug-resistant gramnegative bacteria, particularly Klebsiella species, E coli, Pseudomonas aeruginosa, and Acinetobacter baumannii, have increased, especially among patients in ICUs. Few new antibiotics are being developed to treat these infections. Of the newer antimicrobial agents, only tigecycline has activity against gram-negative pathogens, but it has no clinically relevant activity against Pseudomonas species.33
Adequate antimicrobial therapy, administered early, has a significant impact on the outcome of patients with bacteremia and sepsis. The most common reason for inadequate therapy is resistance to the administered regimen.34 The mechanisms of resistance in these gram-negative bacteria are impermeability of the outer bacterial membrane, efflux pumps, and production of extended-spectrum beta-lactamases (ESBLs).35 ESBLs are enzymes that confer resistance to most betalactam antibiotics, including penicillin, aztreonam, and cephalosporins, by opening the beta-lactam ring with resultant inactivation of the antibiotic. The mutant genes for ESBLs are encoded on transferable plasmids and encode resistance to a variety of antimicrobials in addition to betalactam agents. K pneumoniae and E coli are ESBL-producing organisms; P aeruginosa and A baumannii have extremely impermeable outer membranes and use a variety of mechanisms of resistance that may include ESBL production. Carbapenems, such as imipenem-cilastatin and meropenem, are the drugs of choice for serious infections caused by ESBL-producing bacteria.
Risk factors for colonization and nosocomial infection with multidrug-resistant gram-negative bacteria include patient-topatient transmission, antibiotic use during a hospital stay, and antibiotic use in the person. Prevention methods incorporate infection-control measures and strategies for minimizing total antibiotic use in the hospital. Nosocomial resistant isolates lack options for drug treatment and represent a serious public health concern.
CONCLUSION
The changing epidemiology and resistance patterns of bacteria are making effective treatment of bacterial infections more difficult. Antimicrobial therapy enhances the multiplication of existing drug-resistant bacteria and the exchange of resistance mechanisms among bacteria. Antibiotic administration builds drug resistance in the commensal bacteria that are part of the patient's normal flora as well as in the targeted pathogen, thereby creating a resistance reservoir. Therefore, antibiotic overuse contributes to antimicrobial resistance. Monitoring drug-resistance patterns among pathogens, developing antibiograms for clinicians, and routinely updating the antibiograms are important actions institutions can take to increase awareness of antimicrobial resistance. Local antibiograms that are site-specific to the pathogen and that separate outpatients from inpatients are the most useful. The benefits versus the risks of prescribing antibiotics must be considered. Antibiotic administration puts the patient at risk for allergic reactions, adverse reactions, and drug-drug interactions, as well as increases the likelihood that a newly acquired bacterial infection will be caused by an antibioticresistant strain. From a public health standpoint, indiscriminant use of antibiotics increases the rates of antibiotic resistance in a society. JAAPA
JoAnn Deasy is on the faculty at Pace University-Lenox Hill Hospital Physician Assistant Program, New York, New York. She has indicated no relationships to disclose relating to the content of this article.
DRUGS MENTIONED
Aztreonam (Azactam)
Ciprofloxacin (Cipro, Proquin, generics)
Clindamycin (Cleocin, generics)
Daptomycin (Cubicin)
Imipenem-cilastatin (Primaxin)
Linezolid (Zyvox)
Meropenem (Merrem)
Methicillin
Metronidazole (Flagyl, generics)
Mupirocin (Bactroban, generics)
Nitrofurantoin (Furadantin, Macrobid, Macrodantin, generics)
Penicillin
Quinupristin-Dalfopristin (Synercid)
Rifaximin (Xifaxan)
Tetracycline (Bristacycline, Sumycin)
Tigecycline (Tygacil)
Trimethoprim-sulfamethoxazole (Bactrim, Septra, Sulfatrim, generics)
Vancomycin (Vancocin, generics)
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