Antimicrobial combination therapy with

Antimicrobial combination therapy is used frequently to treat serious infections. Combination therapy may be used prior to knowing the pathogen or antibiotic susceptibility for the treatment of infections in neutropenic patients and in patients with enterococcal endocarditis or bacteremia, sepsis, or pneumonia caused by P. aeruginosa. In these cases, it is important to know whether the combination will have beneficial (or detrimental) effects on the overall antibacterial activity of the regimen. For example, the combination may result in activity that is... 

D. Antimicrobial Drug Combinations Therapy with multiple antimicrobials may be indicated... 

Antimicrobial resistance to rifamycins develops rapidly both in vitro and in vivo [65,85,86], As a consequence, all the three members of the family (i.e. rifampicin, rifabutin and rifapentine) are used clinically as components of combination therapies [65,87], Being structurally related, rifaximin could share this potential. And indeed resistance rates, recorded in fecal strains of Enterobacteriaceae, Enterococcus, Bacteroides, Clostridium and anaerobic cocci, ranged between 30 and 90% after short-term (5 days) antibiotic (800 mg daily) treatment [82], A similar pattern was observed in 10 patients with hepatic encephalopathy after treatment with rifaximin 1,200 mg/day for 5 days [80]. 

Most infections should be treated with a single antimicrobial agent. Although indications for combination therapy exist, antimicrobial combinations are often overused in clinical practice. The unnecessary use of antimicrobial combinations increases toxicity and costs and may occasionally result in reduced efficacy due to antagonism of one drug by another. Antimicrobial combinations should be selected for one or more of the following reasons ... 

To treat polymicrobial infections such as intra-abdominal abscesses. The antimicrobial combination chosen should cover the most common known or suspected pathogens but need not cover all possible pathogens. The availability of antimicrobials with excellent polymicrobial coverage (eg, 13-lactamase inhibitor combinations or imipenem) may reduce the need for combination therapy in the setting of polymicrobial infections. 

Additional challenges are associated with the fact that antimicrobial therapy with EPis is a combination therapy by its very nature. In order to provide the maximum pharmacodynamic benefit, the pharmacokinetics ofthe EPI should be appropriately tailored to the pharmacokinetics of the antibiotic component of the combination. 

An important determinant of successful HP eradication therapy is the presence of preexisting antimicrobial resistance. " " Metronidazole resistance is most common (10% to 60%), but varies depending on prior antibiotic exposure and geographic region. 37,38,49 The clinical importance of metronidazole resistance in eradicating HP remains uncertain, as the synergistic effect of combining metronidazole with other antibiotics appears to render resistance to metronidazole less important. Ehimary resistance to clarithromycin is lower (10% to 15%) than with metronidazole, but it is more likely to affect... 

Combination antimicrobial drug therapy The use of two or more drugs together to increase efficacy more than can be accomplished with the use of a single agent... 

Lind T, Veldhuyzen van Zanten S, Unge P, et al. Eradication of Helicobacter pylori using one-week triple therapies combining omeprazole with two antimicrobials the AAACH I Study. Helicobacter 1996 1 138-144. 

High-dose penicillin G traditionally has been the drug of choice for the treatment of pneumococcal meningitis. However, due to increases in pneumococcal resistance, the preferred empirical treatment now includes a third-generation cephalosporin in combination with vancomycin.13 All CSF isolates should be tested for penicillin and cephalosporin resistance by methods endorsed by the CLSI. Once in vitro sensitivity results are known, therapy may be tailored (Table 67-3). Patients with a history of type I penicillin allergy or cephalosporin allergy may be treated with vancomycin. Treatment should be continued for 10 to 14 days, after which no further maintenance therapy is required. Antimicrobial prophylaxis is not indicated for close contacts. 

Surgical intervention has become an integral therapy in combination with pharmacologic management of IE. Valve replacement is the predominant intervention, and it is used in a minimum of 25% for all cases of IE.1 Surgery may be indicated if the patient has unresolved infection, ineffective antimicrobial therapy (often associated with fungal IE), more... 

Haffajee AD, Uzel NG, Arguello El, Torresyap G, Guerrero DM, Socransky SS Clinical and microbiological changes associated with the use of combined antimicrobial therapies to treat refractory periodontitis. J Clin Periodontol 2004 31 869-877. 

Because of the high morbidity and mortality associated with PVE and refractoriness to therapy, combinations of antimicrobials are usually recommended. 

Serious infections requiring intravenous antimicrobial therapy can be treated with a /S-lactam//S-lactamase inhibitor combination or second-generation cephalosporin with activity against anaerobes (cefoxitin). 

For parenteral therapy, nafciUin and oxacillin offer comparable efficacy and antimicrobial spectra of activity. Although both drugs undergo hepatic metabolism, only nafcillin requires dose adjustment in patients with combined hepatic and renal insufficiency. Other pharmacokinetic data for nafcillin and oxacillin appear in Table 45.1. Indications for nafcillin or oxacillin include severe staphylococcal infections like cellulitis, empyema, endocarditis, osteomyelitis, pneumonia, septic arthritis, and toxic shock syndrome. 

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