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Monday, February 24, 2020

Oral Antibiotic Options for Methicillin-resistant Staphylococcus aureus (MRSA)


Oral Antibiotic Options for Methicillin-resistant Staphylococcus aureus (MRSA)

Methicillin-resistant Staphylococcus aureus (MRSA) in adults: Oral Treatment of Skin and Soft Tissue Infections (SSTI)
Patients with mild infection (localized involvement with no systemic symptoms) due to known or suspected MRSA may be treated with oral antibiotic therapy (kindly refer table below). 
Oral antibiotic agents of choice include trimethoprim-sulfamethoxazole (TMP-SMX), tetracyclines (such as doxycycline or minocycline), or clindamycin. In general, the choice between agents is guided by individual clinical circumstances including local antibiotic resistance patterns, allergy history, and concomitant medications.
The efficacy of clindamycin and TMP-SMX for treatment of uncomplicated skin infection is comparable; in two randomized trials including patients with uncomplicated skin infections, cure rates for clindamycin and TMP-SMX were between 78 and 83 percent. Use of the tetracyclines is supported by susceptibility testing and observational and retrospective reports; their efficacy for treatment of skin and soft tissue infections due to MRSA has not been rigorously evaluated or compared in clinical trials.
In the setting of empiric antibiotic therapy, the efficacy of the above agents against the potential pathogen group A Streptococcus(GAS) should be considered. Clindamycin and TMP-SMX are active against GAS; doxycycline has uncertain activity
Alternative oral agents include oxazolidinones (linezolid and tedizolid), the fluoroquinolone delafloxacin, and the tetracycline omadacycline; use of these drugs is limited by cost, clinical experience, and adverse drug effects. They should be reserved for patients who do not respond to or cannot tolerate other agents.
Fluoroquinolones (apart from delafloxacin) should NOT be used for treatment of skin and soft tissue infections due to MRSA; resistance may develop during therapy.

Oral Treatment (in Adult)
Adult Dose (Normal Renal Function)
Clindamycin
450 mg orally 3 times daily
Doxycycline
100 mg orally twice daily
Linezolid
600 mg orally twice daily
Trimethoprim-sulfamethoxazole
(co-trimoxazole)*
1 or 2 DS tablets twice daily
* DS: double strength (ie, 160 mg trimethoprim with 800 mg sulfamethoxazole per tablet).






MRSA Skin and Soft Tissue Infections  -  Chahine & Sucher (PSAP 2015)
TOPICAL Option
Dosing Regimen (Adults)
Dosing Regimen (Children)
Adverse Effects
Significant Drug Interactions
Mupirocin (ointment, cream)
Skin infections for adults and
children ≥ 2 months: Apply to affected area twice daily for 5 days
MRSA decolonization for
adults and children ≥ 12
years: Apply to anterior nares twice daily for 5 days
Hypersensitivity reactions, skin
irritation, pruritus, burning
-

SYSTEMIC Option
Dosing Regimen (Adults)
Dosing Regimen (Children)
Adverse Effects
Significant Drug Interactions
Clindamycin
300–450 mg PO
four times daily
Adults: 600 mg IV three times daily

20–40 mg/kg/day IV/PO divided into 3 doses
Clostridium difficile infection,
gastrointestinal upset
-
Doxycyline
Adults and children > 45 kg:
100 mg PO twice daily

Children ≥ 8 years and ≤ 45 kg:
2 mg/kg PO twice daily
Gastrointestinal upset,
photosensitivity, permanent
tooth discoloration in children
< 8 years, not recommended for
pregnant women and children <
8 years
Oral cations
Linezolid
Adults and children ≥ 12 years:
600 mg IV/PO twice daily

Children < 12 years: 10 mg/
kg/day IV/PO twice daily
Myelosuppression, neuropathy,
serotonin syndrome
Serotonergic
agents
Trimethoprim/
Sulfamethoxazole
(Bactrim)
Adults: 1 to 2 DS tablet(s) PO twice daily

8–12 mg/kg/day of
trimethoprim divided into 4
doses IV or 2 doses PO
Hypersensitivity reactions,
nausea, vomiting,
myelosuppression,
hyperkalemia, hepatotoxicity,
not recommended for women in
the third trimester of pregnancy
Warfarin,
renin-angiotensin aldosterone system inhibitors
Vancomycin (INTRAVENOUS)
30 mg/kg/day
divided into 2 doses

40 mg/kg/day
divided into 4 doses
Infusion reactions, red man
syndrome, nephrotoxicity
Nephrotoxic
agents

MRSA Infections (Other Sites)  -  IDSA 2011
Manifestation
Treatment
Adult Dose
Paediatric Dose
Strength of Recommen-dation
Comment
Purulent cellulitis
(defined as cellulitis
associated with purulent
drainage or exudate in
the absence of a drainable
abscess)
Clindamycin
300–450 mg PO TID
10–13 mg/kg/dose PO every
6–8 h, not to exceed
40 mg/kg/day
AII
Clostridium difficile–associated
disease may occur more
frequently, compared with
other oral agents.
TMP-SMX
(Bactrim)
1–2 DS tab PO BID
Trimethoprim 4–6 mg/kg/dose,
PO BID
AII
TMP-SMX is pregnancy category C/D and not recommended for women in the third trimester of pregnancy and for children <2 months of age.
Doxycycline
100 mg PO BID
<45kg: 2 mg/kg/dose PO BID .
45kg:
adult dose
All
Tetracyclines are not recommended for children under 8 years of age and are pregnancy
category D.
Linezolid
600 mg PO BID
10 mg/kg/dose PO TID, not to exceed 600 mg/dose
All
More expensive compared
with other alternatives
Nonpurulent cellulitis
(defined as cellulitis with
no purulent drainage
or exudate and no
associated abscess)
Clindamycin
As above
Linezolid
As above
Complicated SSTI
Linezolid
600 mg PO/IV BID
10 mg/kg/dose PO/IV TID
not to exceed
600 mg/dose
AI/AII
For children >12 years of age,
600 mg PO/IV BID. Pregnancy
category C
Clindamycin
600 mg PO/IV TID
10–13 mg/kg/dose PO/IV every
6–8 h, not to exceed
40 mg/kg/day
AIII/AII
Pregnancy category B
Pneumonia
Linezolid
600 mg PO/IV BID
10 mg/kg/dose PO/IV TID
not to exceed
600 mg/dose
AII
For children >12 years of age,
600 mg PO/IV BID. Pregnancy
category C
Clindamycin
600 mg PO/IV TID
10–13 mg/kg/dose PO/IV every
6–8 h, not to exceed
40 mg/kg/day
BIII/AII
Pregnancy category B
Osteomyelitis / Septic arthritis
Linezolid
600 mg PO/IV BID
10 mg/kg/dose PO/IV TID
not to exceed
600 mg/dose
BII/CIII

Clindamycin
600 mg PO/IV TID
10–13 mg/kg/dose PO/IV every
6–8 h, not to exceed
40 mg/kg/day
BIII/AII

TMP-SMX and rifampin
3.5–4.0 mg/kg/dose PO/IV
every 8–12 h
& 600 mg PO QD
No Data (ND)
BII/ND



Alternative dosing for osteomyelitis (from Medscape 2018):
Preferred:
Vancomycin (INTRAVENOUS)
15 mg/kg IV q12hr if MIC
Linezolid
600 mg IV/PO q12hr

Alternative based on results of sensitivity testing and intolerance of vancomycin:
Trimethoprim-sulfamethoxazole

PLUS
Rifampin
4 mg/kg IV q12hr (dose based on trimethoprim component)

600 mg PO q24hr or 300-450 mg PO q12hr

Oral therapy based on results of sensitivity testing:
Doxycycline
100 mg PO q12hr
Clindamycin
450 mg PO q6hr or 600 mg PO q8hr
Trimethoprim-sulfamethoxazole
2 DS tablets PO q8-12hr
Levofloxacin
PLUS
Rifampin
500-750 mg PO daily

600-900 mg PO qd (only if the isolate is sensitive to both antibiotics)




Definitive Prosthetic Joint Infection Treatment       [National Antibiotic Guideline 2019]
Initial treatment:
*Vancomycin 15-20 mg/kg (actual body weight)
IV q8-12h; NOT to exceed 2 gm/dose
PLUS
Rifampicin 300-450 mg PO q12h
·   Duration: 2-6 weeks (according to treatment strategy)
·   Followed by an oral combination therapy according to susceptibility.
·   Rifampicin should be included if implant is in situ


References:
1.       UptoDate: Methicillin-resistant Staphylococcus aureus (MRSA) in adults: Treatment of skin and soft tissue infections
2.       UptoDate: Oral antimicrobial therapy for treatment of skin and soft tissue infections due to methicillin-resistant Staphylococcus aureus (MRSA) in adults (table)
3.       Skin and Soft Tissue Infections - Chahine & Sucher (PSAP 2015). Available from: https://www.accp.com/docs/bookstore/psap/2015B1.SampleChapter.pdf
4.       Practice Guidelines for the Diagnosis and Management of Skin and Soft Tissue Infections: 2014 Update by the Infectious Diseases Society of America.
5.       Clinical Practice Guidelines by the Infectious Diseases Society of America for the Treatment of Methicillin-Resistant Staphylococcus aureus Infections in Adults and Children, 2011.
6.       Medscape: Osteomyelitis Organism-Specific Therapy, 2018. Available from: https://emedicine.medscape.com/article/2018345-overview
7.       National Antibiotic Guideline (Malaysia) 2019

All information accessed on 24.02.2020

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