Monotherapy Versus Combination Therapy Done By: Ohoud AL-Juhani

Outline Introduction Therapies for common infectious diseases Take home messages

Introduction The science of AB therapy for infectious diseases continues to evolve When empiric coverage is necessary, treatment with more than one agent is considered prudent If an etiology is identified, ABS are modified based on culture & susceptibility data

Decision about AB should made after assessment of following factors Pertinent clinical information Laboratory & microbiology information Ease of administration Patient compliance Potential AES Cost Available evidence supporting various treatment options

Cellulitis AB therapy should initially be directed at gram positive organism, such as staph. & strept. as these are the most common organisms responsible for causing cellulitis The cephalosporins are commonly used as 1st line agents because they offer adequate coverage for staph. & strept & are generally well tolerated &effective Cephalexin 500 mg PO Q6 to 12 h is a common regimen & if the patient does not have erysipelas, then dicloxacillin 500 mg PO Q 6 h can also used

Cellulitis Cont… Both of these agents can be used as monotherapy in the setting of uncomplicated cellulitis If Haemophilus influenzae is a potential pathogen, cefuroxime 500 mg PO Q12 h can be used In case of cellulitis that involve gram-negative organism, treatment with fluoroquinolone may be warranted In case of cellulitis that involve MRSA, the oral agents effective against these strain are limited to TMP-SMZ, Clindamycin & Linezolid

Cellulitis Cont… The 2005 IDSA guidelines recommend intial empiric therapy with a penicillinase-resistant penicillin or 1st generation cephalosporin If patient allergic to penicillin, clindamycin or vancomycin can be used In one study that compared tigecycline with combination of vancomycin & aztreonam, clinical cure rates were not found to be significantly different

Cellulitis Cont… In most cases of cellulitis, monotherapy may suffice. However, if there is concern for unusual exposure Or if broader coverage may be needed (e.g.in the setting of immunosuppression or resistant pathogen), Then AB coverage may be broadened to include gram negative organisms & anaerobes

Osteomylitis Ideally, treatment involves organism-specific antimicrobial therapy in conjunction with surgery or debridement if necessary Therapy is often empiric. if patient has an ulcer related to diabetes& the infection is not limb threatening, oral therapy with cephalexin or clindamycin may be tried These agents may not lead to clinical improvement if the causative agent is MRSA

Osteomylitis Cont… If gram-negative are strongly suspected, oral ciprofloxacin 750mg PO BID may be used Monotherapy with gram positive coverage by 1st-generation Cephalosporin,TMP-SMZ, Clindamycin may be attempted in the AB-naïve patient Therapy should be broadened to include gram negative coverage if there was failure with above agents If MRSA is suspected, Linezolide, Daptomycin, or Vancomycin may be used

Osteomylitis Cont… Patient with sever soft tissue infections should receive IV ABs with previous agents in combination Monotherapy is preferred given the needed for long term therapy Decision should be based on epidemiologic factors, culture data & clinical responses whenever possible

Endocarditis Before AB therapy became widely available, endocarditis considered uniformly fatal About 80% of patients today survive with appropriate timely AB therapy It is important to choose bactericidal, not bacteriostatic therapy, to effectively treat endocarditis

Recommendations for endocarditis therapy Organism 1st line ABs Duration MSSA Nafcillin+Gentamicin or Oxacillin+Gentamicin 6 weeks with gentamicin for first 3-5 days MRSA Vancomycin 4-6 weeks Viridans strept. & other strept IV β-lactam with or without aminoglycoside 4-6 weeks, if aminoglycoside used, give for first 2 weeks of therapy Enterococci Ampicillin +gentamicin Coagulase-negative staph. 6 weeks with gentamicin for 1st 3-5 days HACEK Ceftriaxone;or Ampicillin-sulbactam 4 weeks Culture-negative Ampicillin-sulbactam+gentamicin or vancomycin+ciprofloxacin HACEK: Haemophilus parainfluenzae, Actinobacillus actinomycetemcomitans , Cardiobacterium hominis , Eikenella corrodens , Kingella kingae

Diverticulitis Appropriate agents in include a fluoroquinolone with metronidazole, or amoxicillin-clavulanate, or TMP-SMZ with metronidazole Monotherapy with piperacillin-tazobactam or the use of imipenem-cilastatin may be given, but combination of ampicillin, gentamicin & metronidazole can also be effective Monotherapy with moxifloxacin may be considered Tigecycline is also a novel agent currently approved for the treatment of intra-abdominal infections

Pneumonia Community -acquired pneumonia If there is no history of prior AB exposure, monotherapy with azithromycin or clarithromycin, or fluroquinolone may be offered If patients are in ICU & pseudomonas infection is a concern, then an antipseudomonal agent + ciprofloxacin, or an antipseudomonal agent + an aminoglcocoside + a respiratory fluroquinolone or a macrolide may be used

Pneumonia Cont… Patient who have been exposed to a nursing home should be treated following the same guidelines However in this patients, amoxicillin-clavulante+ a macrolide (or a respiratory fluroquinolone alone) is an appropriate alternative

Combination therapy versus monotherapy for ventilator associated pneumonia Combination AB therapy for VAP is often used to broaden the spectrum of activity of empirical treatment In randomized pilot study patients with VAP were prospectively randomised to receive either cefepime alone or cefepime in association with amikacin or levofloxacin AB combination using a 4th generation cephalosporin with either an amikacin or levofloxacin is not associated with a clinical or biological benefit when compared to cephalosporin monotherapy

Meningitis Empiric therapy should cover most of the common causes of bacterial meningitis 3rd generation cephalosporins, such as cefotaxime 2g IV Q6h & ceftriaxone 2g BID have become the mainstay of initial therapy for bacterial meningitis If Listeria monocytogenes suspected, then penicillinG 4 MU IV Q4 h or ampicillin 2g IV Q4 h + gentamicin for synergy must be added for appropriate coverage

Meningitis Cont… In most common cases of bacterial meningitis, initial combination therapy is recommended, with modifications in the AB regimen once further culture information become available

Management of Neutropenic Fever

Take home messages Several treatment options are available for patients with these common infectious diseases When empiric treatment is needed, combination therapy is often advised In all cases, the potential risk/benefit of combination therapy versus monotherapy must be considered If hospitalized patients are treated with parentral AB, they should be switched to an oral regimen once clinical improvement occur, if appropriate

References Shilpa M. Patel, MD Louis D. Saravolatz, MD, MACP Med Clin N Am 90 (2006) 1183-1195 http://creativecommons.org/licenses/by/2.0

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