ANTIBIOTICS ADMINISTRATION IN CRITICAL ILL

PATIENT WITH METHICILLIN RESISTANT

STAPHYLOCOCCUS AUREUS (MRSA)
PRATIWI QURANITA
SUDIRMAN KATU
 Background
“ Diagnostic techniques and
identification of bacterial are quite
expensive and not available at
all institutions

Combination antibiotic therapy

resistant microorganisms.

Within ± 50 years, there has been

an increase in the incidence of
infections caused by
microorganisms that are resistant
to various antimicrobial or
antibiotic agents.

increased morbidity, mortality,

“
and costs.

Vitrat, dkk. Optimizing antimicrobial therapy in critically ill patients. Infection and Drug Resistance 2014:7 261–271.
IOWA. Methicillin Resistant Staphylococcus aureus. 2016. USA. 1(1): p.1-27
Costa AR et al. Staphylococcus aureus virulence factors and disease. 2013. Portugal. 1(1): p.1-9
 S. aureus
• Staphylococcaceae family.
• gram-positive cocci with a diameter of ± 1 μm
• produces toxins (cytotoxins, pyrogenic
superantigens, enterotoxins and exfoliative
toxins)
• produces various kinds of enzymes
(protease, lipase, and hyaluronidase which
help spread the infection)

Costa AR et al. Staphylococcus aureus virulence factors and disease. 2013. Portugal. 1(1): p.1-9
Tong SYC et al. Staphylococcus aureus Infections: Epidemiology, Pathophysiology, Clinical Manifestations, and Management. 2015. USA. 28(3): p.1-59
Taylor TA & Unakal CG. Staphylococcus Aureus. 2017. USA. Internet. Available from: https:// www. ncbi. nlm. nih. Gov / books / NBK441868/
 Chronology of S. aureus infection and resistance

1940 1959 MRSA is a major cause

of infection in hospitals and
benzyl-penicillin (penicillin G) Methicillin was first introduced in
temporarily solved the problem of 1959 to treat infections caused has expanded rapidly in
infection with Staphylococcus aureus. by penicillin-resistant S. aureus
types many parts of the world. It is
also increasingly being
rediscovered from patients
in long-term care facilities
such as elderly houses, and

1950 1961 even from people in the

these microorganisms are resistant reports suggesting that S. aureus community or in sports
to almost all systemic antibiotics, has become resistant to venues
including erythromycin, streptomycin methicillin
and tetracyclin

IOWA. Methicillin Resistant Staphylococcus aureus. 2016. USA. 1(1): p.1-27

Costa AR et al. Staphylococcus aureus virulence factors and disease. 2013. Portugal. 1(1): p.1-9
Liu C et al. Clinical Practice Guidelines by the Infectious Diseases Society of America for the Treatment of Methicillin-Resistant Staphylococcus Aureus Infections in Adults and Children. 2011. USA.
52(1): p.1-38
Paiva JA & Eggiman P. Treatment of severe MRSA infections: current practice and further development. 2017. Portugal. 43(1): p.233-236
 Healthcare-associated MRSA
Disease Control and Prevention (CDC)

"MRSA infections that occur in individuals who have been

hospitalized or undergo surgery for the past 1 year, have
permanent medical aids in their bodies, live in long-term care
facilities, or individuals undergoing dialysis."

Paiva JA & Eggiman P. Treatment of severe MRSA infections: current practice and further development. 2017. Portugal. 43(1): p.233-236
Tong SYC et al. Staphylococcus aureus Infections: Epidemiology, Pathophysiology, Clinical Manifestations, and Management. 2015. USA. 28(3): p.1-59
 Community-associated MRSA
In the early 1990s MRSA emerged which was found in
individuals who had no risk factors associated with MRSA
before.

The CA-MRSA strain typically contains exotoxins

called Panton-Valentine Leukodin (PVL) toxin. PVL is
often present in immunocompetent patients in the
absence of identifiable risk factors.

Costa AR et al. Staphylococcus aureus virulence factors and disease. 2013. Portugal. 1(1): p.1-9
Tong SYC et al. Staphylococcus aureus Infections: Epidemiology, Pathophysiology, Clinical Manifestations, and Management. 2015. USA. 28(3): p.1-59
Taylor TA & Unakal CG. Staphylococcus Aureus. 2017. USA. Internet. Available from: https:// www. ncbi. nlm. nih. Gov / books / NBK441868/
 Characteristics between HA-MRSA and CA-MRSA
HA-MRSA CA-MRSA
At-risk groups or conditions Residents in long-term care facility, Children, competitive athletes,
patients with diabetes mellitus, prisoners, soldiers, selected ethnic
patients undergoing populations (Native Americans/
hemodialysis/peritoneal dialysis, Alaska Natives, Pacific Islanders),
prolonged hospitalization, intensive intravenous drug users, men who
care unit admission, indwelling have sex with men
intravascular catheters
SCC type Types I, II, & III Type IV & V
Strain type USA 100 & 200 USA 300 & 400
Antimicrobial resistance Multidrug resistance, common β-Lactam resistance alone, common
PVL toxin Rare (5%) Frequent (almost 100 %)
Associated clinical syndromes Nosocomial pneumonia, Skin and soft tissue infections
nosocomial- or catheter-related (furuncles, skin abscesses),
urinary tract infections, intravascular postinfluenza necrotizing pneumonia
catheter or bloodstream infections,
surgical-site infections
Liu C et al. Clinical Practice Guidelines by the Infectious Diseases Society of America for the Treatment of Methicillin-Resistant Staphylococcus Aureus Infections in Adults and Children. 2011. USA.
52(1): p.1-38
Paiva JA & Eggiman P. Treatment of severe MRSA infections: current practice and further development. 2017. Portugal. 43(1): p.233-236
Tong SYC et al. Staphylococcus aureus Infections: Epidemiology, Pathophysiology, Clinical Manifestations, and Management. 2015. USA. 28(3): p.1-59
Critical ill patient
dysfunction or failure of one or more
organs / organ systems

the disease process causes physiological

instability that causes disability or death
within minutes or hours.

its survival depends on monitoring

instruments

The safest place for patients who experience

critical illness is in the intensive care unit
(ICU)
Gupta S., et al. Guidelines for the Transport of Critically Ill Patients. Postgraduate, 2004: 6(2); 1-4
Frost, P. dan Matt PW. Recognition and Early Management of the Ill Ward Patients. British Journal of
Hospital Medicine, 2007: 68(10); 1-4
 Sepsis
drug pharmacokinetics
Society of Critical Care Medicine antibiotics and pharmacodynamics
(SCCM) dan the European
Society of Intensive Care
Medicine (ESICM), 2016

Sepsis is a "life-threatening organ

dysfunction caused by a regulated age, weight, degree of
host response to infection" host infection, comorbid
Empirical
therapy

bacterial resistance and

agent sensitivity

Rello J, Valenzuela-Sanchez F, dan Ruiz-Rodriguez M. (2017). Sepsis: A Review od Advances in Management. Adv Ther, 34; 2393-2411
Levy M.M, et al. (2018). The Surviving Sepsis Campaign Bundle: 2018 Update. Critical Care Medicine, 46(6), 1-4.
Kementerian Kesehatan Republik Indonesia. Pedoman Nasional Pelayanan Kedokteran Tata Laksana Sepsis. Jakarta : 2017
 Sepsis-outpatient

For outpatients, emergency unit, or hospital wards, adult

patients with suspected infection can be identified quickly to
have a higher risk of experiencing sepsis if they have at least 2
clinical criteria from a quick SOFA bedside clinical score
(qSOFA)

Singer, M., Deutschman,C.S., Seymour,C.W., Shankar-Hari, M., Annane, D.,Bauer, M.,...Angus, D. C. (2016). The Third International consensus Definitions for Sepsis and Septic shock (Sepsis-3). Jama, 315(8),801-
810
Taeb A.M. et al. (2013). Sepsis: Current Definition, Pathophysiology, Diagnosis and management. Nutrition in Clinical Practice, 20(10),1-13
 Sepsis- hour-1 bundle
"Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016"

For sepsis with unclear sources of infection:

• (Piperacilin / tazobactam * 4.5 gr IV / 6 hours or cefepime * 2 gr
IV / 8 hours) +/- vankomicin +/- gentamicin,

Severe PCN allergy:

• (Aztreonam 2 gr IV / 8 hours or ciprofloxacin 400 mg IV / 8
hours) + gentamicin plus vancomycin

*: if the patient has a history of ESBL-producing organism or is suspected of intra-

abdominal sepsis and has just received piperacillin / tazobactam or long-term cefepime (≥
7 days), replaced by meropenem 1 gr IV every 8 hours. 21 In MRSA bacterial S.aureus:
vancomycin 15mg / kg IV / 12 hours, or daptomycin 6 mg / kg IV every 24 hours

Levy M.M, et al. (2018). The Surviving Sepsis Campaign Bundle: 2018 Update. Critical Care Medicine, 46(6), 1-4.
Cosgrove SE., et al. Antibiotic guidelines 2015-2016: Treatment recommendation for adult inpatients. John Hopkins Medicine.
Neeman, K., Mark R., Trevor VS. 2014. Staphylococcus aureus bloodstream infection treatment guidelines
 Mild-moderate :
• Ceftriaxon * 1 gr IV every 24 hours.
Severe (ICU):
• Cefepime * 2 gr IV every 8 hours +/- Vancomicin
COMMUNITY-ACQUIRED PNEUMONIA
Piperacillin / tazobactam * 4.5 gr IV every 6 hours +/-
pneumonia obtained from outside the hospital, the vancomicin
diagnosis is usually confirmed by a chest radiograph
• Severe PCN allergy: vancomicin plus ciprofloxacin
400 mg IV every 8 hours +/- Gentamicin

with cavities without risk of aspiration HOSPITAL-ACQUIRED PNEUMONIA

• Linezolid 600 mg IV / PO every 12 hours peumonia which develops at 48 hours or more after being admitted
can be added while waiting for culture to the hospital and not during the incubation period upon admission
results. to the hospital, the diagnosis is confirmed by a chest radiograph.

Patients at risk of MRSA:

• Levofloxacin 750 mg IV per day / Ciprofloxacin 400 mg IV every 8
hours or
• imipenem 500 mg IV every 8 hours / meropenem 1 gr IV every 8
hours or
• aztreonam 2 gr IV every 8 hours.
Then added
• Vancomicin 15 mg / kg IV every 8-12 hours (consider 25-30 mg / kg x
1 loading dose for severe pain) or
• Linezolid 600 mg IV every 12 hours.

Cosgrove SE., et al. Antibiotic guidelines 2015-2016: Treatment recommendation for adult inpatients. John Hopkins Medicine.
Cao B., et al. Consensus statement on the management of methicillin-resistant staphylococcus aureus nosocomial pneumonia in Asia.
The Clincial Respiratory Journal, 2015: 1-14
Cosgrove SE., et al. Antibiotic guidelines 2015-2016: Treatment recommendation for adult inpatients. John Hopkins Medicine.
Cao B., et al. Consensus statement on the management of methicillin-resistant staphylococcus aureus nosocomial pneumonia in Asia. The Clincial Respiratory Journal, 2015: 1-14
 • piperacilin / Fazobactam 3,375 gr IV every 6 hours., or
• cefepime 1 gr IV every 8 hours + metronidazole 500 mg
IV every 8 hours (allergic PCN is not severe), or
Cholecystitis and • Ciprofloksasin 400 mg IV every 12 hours or Aztreonam
1 gr IV every 8 hours + metronidazole 500 mg IV every
Cholangitis 8 hours (severe PCN allergy)

Community-acquired infections
• Ceftriaxon 1 gr IV every 24 hours or Ertapenem 1 gr IV every Diverculitis
24 hours, or
• Ciprofloksasin 400 mg IV every 12 hours (severe PCN
allergies)
Hospital-acquired infections
• piperacilin / tazobactam 3.375 g every 6 hours, or
• cefepime 1 gr IV every 8 hours + metronidazole 500 mg IV
every 8 hours (allergic PCN is not severe), or
• aztreonam 1 gr IV every 8 hours plus metronidazole 500 mg
IV every 8 hours +/- Vancomicin. (severe PCN allergy)

Cosgrove SE., et al. Antibiotic guidelines 2015-2016: Treatment recommendation for adult inpatients. John Hopkins Medicine.
Sartelli M., et al. The management of intra-abdominal infections from a global perspective: 2017 WSES guidelines for management of intra-abdominal infections. World Journal of Emergency Surgery, 2017: 12(29);
1-34
 Primary peritonitis / spontaneous bacterial
peritonitis
• Ceftriaxon 1 gr IV every 12 hours
Secondary peritonitis
• Ertapenem 1 gr IV every 24 hours or Ciprofloksasin
Pancreatitis 400 mg IV every 12 hours plus metronidazole 500 mg
IV every 8 hour (severe PCN allergy)

• piperacilin-tazobactam 4,5 gr IV every 6 hours. cefepime

1 gr IV every 8 hours plus metronidazole 500 mg IV Peritonitis
every 8 hours (allergic PCN is not severe), or
• ciprofloksasin 400 mg IV every 12 hours plus
metronidazole 500 mg IV every 8 hours . (severe PCN
allergy)

Cosgrove SE., et al. Antibiotic guidelines 2015-2016: Treatment recommendation for adult inpatients. John Hopkins Medicine.
 The most important treatment is the patient's catheter must
be removed if possible. Stable patients with no evidence of
upper UTI
• ertapenem 1 g IV every 24 hours or
IVCatheter associated- • ceftriaxone 1 g IV every 24 hours or
infection • ciprofloxacin 500 mg PO bid or 400 mg IV every 12 hours

Vancomycin is recommended as an empirical

therapy for methicillin-resistant Staphylococcus Catheter associated-bacteriuria
aureus, for vancomycin minimum inhibitory
concentration> 2 μg / mL, alternative agents
such as daptomycin, must be used

Cosgrove SE., et al. Antibiotic guidelines 2015-2016: Treatment recommendation for adult inpatients. John Hopkins Medicine.
Gahlot, R., et al. Catheter-related bloodstream infections. International Journal of Critical Illness and Injury Science, 2014: 4(2); 1-7
Mermel L., et al. Clinical practice guidelines for the diagnosis and management of intravascular catheter-related infection: 2009 update by the infectious diseases society of America. IDSA guidelines for Intravascular
Catheter-related Infection, 2009: 49(7); 1-45
 Degree Management
Mild infection Amoxicillin / clavulanate 875 mg PO bid
Cephalexin 500 mg PO qid
Clindamycin 300 mg PO (covers MRSA)
Parenteral regimen: Clindamycin 600 mg IV every 8 hours (covers
MRSA)
Oksacillin 1-2 gr IV every 4 hours
Cefazolin 1 gr IV every 8 hours
Moderateinfection Ertapenem 1 gr every 24 hours
(ciprofloxacin 500 mg bid or ciprofloxacin 400 mg IV every 12
hours) plus one of (clindamycin 600 mg IV every 8 hours or 300 mg
Cellulitis PO tid or metronidazole 500 mg IV / PO tid)
But avoid fluoroquinolones in outpatients
Severe infection Piperasilin / tazobactam 4.5 gr IV every 6 hours
(Ciprofloxacin 400 mg IV every 8 hours or aztreonam 2 gr IV every
Oral administration in mild cases 8 hours) plus clindamycin 600 mg IV every 8 hours
• TMP / SMX 1-2 DS tab PO bid or Avoid using fluoroquinolones in outpatients
• doxycycline 100 mg PI bid or If the patient is at Piperasilin / tazobactam 4.5 gr IV every 6 hours plus vancomycin
risk for MRSA
• Minocycline 100 mg PO bid or (Ciprofloxacin 400 mg IV every 8 hours or
• clindamycin 300 mg PO every 8 hours or aztreonam 2 gr IV every 8 hours) metronidazole 500 mg IV every 8
clindamycin 500 mg IV every 8 hours hours plus vancomycin
Avoid using fluoroquinolones in outpatients
Parenteral (for moderate to severe cases)
with vancomycin
Diabetic foot ulcer

Cosgrove SE., et al. Antibiotic guidelines 2015-2016: Treatment recommendation for adult inpatients. John Hopkins Medicine.
Phoenix G, Saroj D, dan Meera J. Diagnosis and management of cellulitis. BMJ, 2012: 345; e4955
Conclusion
Rational and effective
The rational, effective and safe treatment must actually apply to all treatment measures taken by the
medical profession and not only limited to the use of antibiotics.

Vancomycin
critically ill patients, individual vancomycin doses, at AUC / MIC levels ≥ 400

Linezolid and daptomycin

HAP / VAP MRSA and MRSA bacteremia, linezolid and daptomycin may be better

Vancomycin or daptomycin
difficult to treat cases of MRSA bacteremia, a combination of vancomycin or daptomycin with anti-
staphylococcal β-lactam can improve results in terms of microbiological eradication.
Thank you