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 4-6 weeks

Coagulase-negative staph. Vancomycin 6 weeks with gentamicin for 1st 3-5 days

HACEK Ceftriaxone;or Ampicillin-sulbactam

4 weeks

Culture-negative Ampicillin-sulbactam+gentamicin or vancomycin+ciprofloxacin

4-6 weeks

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

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