Switch Therapy pada Sepsis Pneumonia

Akibat Pseudomonas

Herdiman T. Pohan
Division of Tropical and Infectious Diseases
Department of Internal Medicine Faculty of Medicine Universitas Indonesia
 Clinical Syndromes of Pseudomonas Infection

• Pneumonia VAP and neutropenic host

• Exacerbation of cystic fibrosis
• Primary bacteremia in neutropenic and HIV-
infected individuals with CD4<50 cells/mm3
• Right-sided native valve endocarditis in iv drug
users and left-sided early prosthetic valve
endocarditis
• Malignant external otitis in diabetics

Giamarellou H. J. Antimicrob. Chemother. 2002:229-33.

 Clinical Syndromes of Pseudomonas Infection

Nosocomial meningitis and brain abscesses after

neurosurgery and fractures of the base of the skull
Endophtalmitis complicating penetrating injuries,
intraocular surgery and contaminated artificial
lenses
Osteomyelitis due to hematogenous spread,
trauma and orthopaedic surgery whenever
prosthethis are implanted
Soft tissue infections complicating severe burns
Giamarellou H. J. Antimicrob. Chemother. 2002:229-33.
 When to Suspect P. aeruginosa?

• Retrospective analysis from 4 hospitals

• 151 patients and 152 controls
– P. aeruginosa caused 6.8% of 4,114 episodes of Gram-
negative bacteremia
– Risk factors: severe immunodeficiency, age >90,
antimicrobials within 30 days, presence of central venous
catheter or a urinary device
• If ≥2 had over 25% risk for P. aeruginosa

V Schechner et al, CID 48:580-6, 2009

Etiology of Pneumonia:
Role of Pseudomonas

Kollef MH, et al. Chest .2005;128:3854-62.

Carratala J, et al. Arch Intern Med. 2007;167:1393-99.
Micek ST, et al. Antimicrob Agents Chemother. 2007; 51:3568-73.
Shindo Y, et al. Chest 2008.
Etiology of Pneumonia, RSCM Jan-June 2013:
Role of Pseudomonas (n=1.689)
1%
1%
1%

1%
1% 1% 4% Klebsiella pneumoniae
Acinetobacter baumanii
5%
Pseudomonas aeruginosa
31% Escherichia coli
7%
Enterobacter aerogenes
Acinetobacter Iwoffii
7% Klebsiella oxytoca
Citrobacter freundii
Serratia marcescens
Stenotrophomonas maltophilia
17% Enterobacter cloacae
Citrobacter freundii
23%
Others

Patologi Klinik RSCM. 2013

 Risk Factors for P. aeruginosa in Pneumonia

• Repeat exacerbations of severe COPD

• Structural lung disease (bronchiectasis)
• Corticosteroids (> 10 mg prednisone/day)
• Broad-spectrum antibiotics for > 7 days within
the past month
• Malnutrition
• Late-onset HAP (>5 days)

CID 2007:44 (Suppl 2): S49.

AMJRCCM 1999:160.
Semin Resp Infect 13:1998.
Infect Dis Clin North Amer 12:1998.
 Antimicrobial Choices for Pseudomonas
Antibiotics Classification Drugs
Antipseudomonas Ceftazidime, cefepime,
cephalosporin cefpirome
Beta-lactam/ beta-lactam Piperacillin-tazobactam
inhibitor
Carbapenem Imipenem, meropenem,
doripenem
Antipseudomonas Ciprofloxacin, levofloxacin,
fluoroquinolone Moxifloxacin
Aminoglycosides Amikacin, tobramycin,
gentamicin
Monobactam Aztreonam

Gomez MP, et al. Journal of Biomaterials and Nanotechnology. 2012:519-27.

Antimicrobial Choices for Pseudomonas

Mesaros N, et al. Clin Microbiol Infect 2007; 13: 560–78.

 Rule of Empiric Therapy for Suspected
Pseudomonas Pneumonia
• An antipneumococcal, antipseudomonal
b-lactam (piperacillin tazobactam,
cefepime, imipenem, or meropenem)
• Plus:
– Ciprofloxacin or levofloxacin (750 mg)
– An aminoglycoside and azithromycin
– An aminoglycoside and an antipneumococcal
fluoroquinolone
Mandell LA, et al. CID 2007:44 (Suppl 2): S49.
 When Can We Switch i.v. → p.o.?
Criteria for clinical stability
• Temperature <37.8oC
• Heart rate <100 beats/min
• Respiratory rate <24 breaths/min
• Systolic blood pressure >90 mm Hg
• Arterial oxygen saturation >90% or pO2
>60 mm Hg on room air
• Ability to maintain oral intake
• Normal mental status
Mandell LA, et al. CID 2007:44 (Suppl 2): S49.
 Types of i.v. → p.o. Conversion
• Sequential therapy:
▫ Parenteral version of a medication with its oral
counterpart.
▫ Levofloxacin i.v. → levofloxacin p.o.
• Switch therapy:
▫ IV medication to the PO equivalent that may be within
the same class and have the level of potency, but is a
different compound.
▫ Moxifloxacin i.v. → levofloxacin p.o.
• Step-down therapy:
▫ IV medication to an oral agent in another class or to a
different medication within the same class

Kuper KM. Intravenous to oral therapy conversion. 2008.

 Antibiotics in Conversion Program
Sequential and Switch Step-down Therapy
Therapy
Azithromycin Ampicillin → amoxicillin
Cefuroxime Ampicillin/sulbactam →
Ciprofloxacin amoxicillin/clavulanate
Clindamycin Piperacillin/tazobactam (multiple
Doxycycline options)
Levofloxacin Ticarcillin/clavulanic acid
Linezolid (multiple options)
Metronidazole Aztreonam → ciprofloxacin or
Moxifloxacin levofloxacin
Sulfamethoxazole/trimethoprim Cefazolin → cephalexin
Cefotaxime or ceftriaxone →
cefpodoxime or cefuroxime axetil
Ceftazidime, cefepime →ciprofloxacin or
levofloxacin
Kuper KM. Intravenous to oral therapy conversion. 2008.
 What are the Antibiotic of Choice?

• In general, either the same agent as the

intravenous antibiotic or the same drug class
should be used
• Switching to a different class of agents simply
because of its high bioavailability is probably
not necessary for a responding patient

Mandell LA, et al. CID 2007:44 (Suppl 2): S49.

 Antimicrobial Choices for Pseudomonas
Antibiotics Classification Drugs
Antipseudomonas Ceftazidime, cefepime,
cephalosporin cefpirome
Beta-lactam/ beta-lactam Piperacillin-tazobactam
inhibitor
Carbapenem Imipenem, meropenem,
doripenem
Antipseudomonas Ciprofloxacin, levofloxacin
fluoroquinolone
Aminoglycosides Amikacin, tobramycin,
gentamicin
Monobactam Aztreonam
Gomez MP, et al. Journal of Biomaterials and Nanotechnology. 2012:519-27.
Oral Bioavailability of Selected Medications
Available in Both IV and PO Formulations

Kuper KM. Intravenous to oral therapy conversion. 2008.

 When does the physician need high dose
levofloxacin?

• Complicated skin and skin structure infections

• Meningitis
• Pneumonia
• Legionellosis
• Endocarditis due to viridans group streptococci
• Pseudomonas aeruginosa infection

Graniwer W, 2004
 Killing-versus-time curves for clinical isolates of
S. aureus (MIC 0.5 g/ml) and P. aeruginosa (MIC 2 g/ml):
Relevance of Soft-Tissue Penetration by Levofloxacin

Individual differences in the tissue penetration of levofloxacin may markedly affect target site
killing of bacteria for which MICs are close to 2 g/ml

Zeitlinger MA, et al. Antimicrob Agents Chemother 2003; 47: 3548-53.

 Steady-State Intrapulmonary Concentrations of
Levofloxacin in Healthy Adult Subjects

ELF=epithelial lining fluid; AM=alveolar macrophage Gotfried MH. Chest 2001; 119: 1114-22.
 Conclusion
• High dose levofloxacin has a role in switch
therapy of:
– Certain clinical syndromes: SSTI, meningitis, pneumonia
– Certain infections: Legionela, S. viridans, P. aeruginosa
• In post P. aeruginosa pneumonia, levofloxacin is
a drug of choice due to:
– Its high biovalaibility
– The only classes of oral anti-Pseudomonas antibiotics