1. Monotherapy Versus Combination Therapy
Done By: Ohoud AL-Juhani

2. Outline Introduction Therapies for common infectious diseases
Take home messages

3. 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

4. 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

7. 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

8. 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

9. 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

10. 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

11. 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

12. 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

13. 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

14. 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

15. 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

16. 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

17. 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

18. 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

19. 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

20. 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

21. 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

22. Management of Neutropenic Fever

24. 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

25. References
Shilpa M. Patel, MD Louis D. Saravolatz, MD, MACP Med Clin N Am 90 (2006)

26. Thank You