Hospital-acquired pneumonia medical therapy

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Editor(s)-in-Chief: C. Michael Gibson, M.S., M.D. ; Philip Marcus, M.D., M.P.H.Associate Editor(s)-in-Chief: Chetan Lokhande, M.B.B.S [1]; Alejandro Lemor, M.D. [2]

Overview

Methicillin-resistant staphylococcus aureus is a common isolate in the patients with Hospital-acquired pneumonia. The treatment options commonly used are vancomycin, linezolid, and clindamycin. Linezolid may be preferred in patients with renal insufficiency as the nephrotoxicity with Linezolid is less compared to vancomycin. Additionally, in patients with vancomycin MIC ≥ 2mcg/mL linezolid is preferred. Linezolid resistance and failure are rare.

Medical Therapy

According to the IDSA guidelines the treatment regimen will depend on the risk factors and the likelihood of drug resistance

Empirical Therapy

Empirical Regimens   ▸   No Risk Factors for MDR   ▸  Presence of Risk Factors for MDR

No Risk Factors for MDR Preferred Regimen ▸ Ceftriaxone 1-2 g q24h IV or IM (max: 4 g/day) OR ▸ Levofloxacin 750 mg q24h for 7-14 days OR ▸Moxifloxacin 400 mg PO/IV q24h for 7-14 days OR ▸Ciprofloxacin 400 mg PO q8h for 10-14 days OR ▸ Ampicillin sulbactam 1-2 g q6-8h IV/IM (max: 8 g/day). OR ▸ Ertapenem 1 g IM/IV q24h for 10-14 days Presence of Risk Factors for MDR Preferred Regimen ▸ Cefepime 1–2 g q8–12h OR ▸ Ceftazidime 2 g q8h OR ▸Imipenem 500 mg q6h or 1g q8h OR ▸Meropenem 1 g q8h OR ▸ Piperacillin-tazobactam 4.5 g q6h PLUS ▸Ciprofloxacin 400 mg q8h OR ▸Levofloxacin 750 mg q24h OR ▸ Amikacin† 20 mg/kg per day OR ▸Gentamycin† 7 mg/kg per day OR ▸Tobramycin† 7 mg/kg per day PLUS ▸ Linezolid 600 mg q12h OR ▸Vancomycin‡ 15 mg/kg q12h † Trough levels for gentamicin and tobramycin should be less than 1 g/ml, and for amikacin they should be less than 4–5 g/ml. ‡ Trough levels for vancomycin should be 15–20 g/ml

Risk factors for MDR pathogens
Antimicrobial therapy in preceding 90 days
Current hospitalization of ≥ 5 days
High frequency of antibiotic resistance in the community or in the specific hospital unit
Immunosuppressive disease and/or therapy
Presence of risk factors for HCAP: Hospitalization ≥2 days in the preceding 90 days Residence in a nursing home or extended care facility Home infusion therapy (including antibiotics) Chronic dialysis within 30 days Home wound care Family member with multidrug-resistant pathogen

List of potential pathogens based on the presence of risk factors for MDR

No Risk Factors for MDR	Presence of Risk Factors for MDR
Streptococcus pneumoniae	Streptococcus pneumoniae
Haemophilus influenzae	Haemophilus influenzae
Methicillin-sensitive Staphylococcus aureus	Methicillin-sensitive Staphylococcus aureus
Antibiotic-sensitive enteric gram-negative bacilli	Antibiotic-sensitive enteric gram-negative bacilli
Escherichia coli	Escherichia coli
Klebsiella pneumoniae	Klebsiella pneumoniae
Enterobacter species	Enterobacter species
Proteus species	Proteus species
Serratia marcescens	Serratia marcescens
	Pseudomonas aeruginosa
	Klebsiella pneumoniae
	Acinetobacter species
	Methicillin-resistant S. aureus (MRSA)
	Legionella pneumophila

Special Considerations

Methicillin-Resistant Staphylococcus Aureus

High Risk Patients

• Critically ill patients
• History of recent antibiotic therapy
• Patient admitted in a hospital with increased incidence of MRSA.

Antibiotic Choice for MRSA

• Vancomycin (15-20 mg/kg q8hr or q12 hr in patients with normal renal function and target vancomycin of 15 - 20 mg/L)
• Linezolid - 600 mg twice daily IV or orally
• Teicoplanin
• Clindamycin if documented susceptibility present
• In case no MRSA is isolated on culture these antibiotics should be discontinued.

Advantages of Linezolid over Vancomycin

Methicillin-resistant staphylococcus aureus is a common isolate in the patients with Hospital-acquired pneumonia. The treatment options commonly used are vancomycin, linezolid, and clindamycin. Linezolid may be preferred in patients with renal insufficiency as the nephrotoxicity with linezolid is less compared to vancomycin. Additionally, in patients with vancomycin MIC ≥ 2mcg/mL linezolid is preferred. Linezolid resistance and failure are rare.

Side-effects of Linezolid

• Thrombocytopenia
• Gastrointestinal side-effects
• Renal dysfunction

Side-effects of Vancomycin

• Renal toxicity were more common in vancomycin compared to linezolid

Vancomycin Trough

• The target vancomycin trough concentrations is 15 to 20 mcg/mL , , .

Supportive Trial Data

In a study done in 1184 patients treated with linezolid and vancomycin no significant difference in 60 days mortality were found between the two groups. The side-effects profile were similar in both the groups however nephrotoxicity was commoner in the vancomycin group. Linezolid was found to be non-inferior to vancomycin for clinical outcome, and microbiologic outcome at end of treatment and end of study.

Methicillin Sensitive Staphylococcus Aureus

• If the culture grows methicillin sensitive staphylococcus aureus then empiric treatment for MRSA should be stopped and MSSA agents such as nafcillin (2g iv Q4hrly) or oxacillin (2g iv Q4hrly) should be started.

Gram Negative Pathogen

• There is a lack of consensus regarding the choice of antibiotics for gram negative pathogens in ventilator associated pneumonia, and health care associated pneumonia.
• Large randomized clinical trials regarding the choice of anti-microbial agents in these conditions are lacking.
• Many hospitals prefer combination drug therapy over monotherpy in these conditions. The rationale behind these are:
  • Wide coverage of pathogenic strains
  • Avoidance of development of antibiotic resistant strains.
  • In ICU settings cephalosporins should be avoided as monotherapy, due to problems of developments of resistant organism.
  • The preferred agants in ICU settings are: carbapenem (ertapenem, meropenem, doripenem, and imipenem-cilastatin).

Legionella

At Risk Population

• Diabetes mellitus
• Chronic renal insufficiency
• Pulmonary diseases
• Glucocorticoids
• Hospitals with water supplies infected with legionella

Anti-Microbial Agents

• Azithromycin
• Fluoroquinolones

Anaerobes

Anti-Microbial Agents

• Clindamycin
• A beta-lactam-beta-lactamase inhibitor combination
• Carbapenem

Major Points and Recommendations for Initial Antibiotic Therapy in Adults with Hospital-Acquired, Ventilator-Associated, and Healthcare-Associated Pneumonia

“

Major Points and Recommendations for Initial Antibiotic Therapy Choice of specific agents should be dictated by local microbiology, cost, availability, and formulary restrictions (Level II). Patients with healthcare-related pneumonia should be treated for potentially drug-resistant organisms, regardless of when during the hospital stay the pneumonia begins (Level II) Inappropriate therapy (failure of the etiologic pathogen to be sensitive to the administered antibiotic) is a major risk factor for excess mortality and length of stay for patients with HAP, and antibiotic-resistant organisms are the pathogens most commonly associated with inappropriate therapy (Level II) In selecting empiric therapy for patients who have recently received an antibiotic, an effort should be made to use an agent from a different antibiotic class, because recent therapy increases the probability of inappropriate therapy and can predispose to resistance to that same class of antibiotics (Level III) Initial antibiotic therapy should be given promptly because delays in administration may add to excess mortality resulting from VAP (Level II) Initial empiric therapy is more likely to be appropriate if a protocol for antibiotic selection is developed on the basis of the recommendations in Tables 2–4, but adapted to local patterns of antibiotic resistance, with each ICU collecting this information and updating it on a regular basis (Level II)

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For Level of evidence and classes click here.

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Major Points and Recommendations for Selected MDR Pathogens If Pseudomonas aeruginosa pneumonia is documented, combination therapy is recommended. The principal justification is the high frequency of development of resistance on monotherapy. Although combination therapy will not necessarily prevent the development of resistance, combination therapy is more likely to avoid inappropriate and ineffective treatment of patients (Level II). If Acinetobacter species are documented to be present, the most active agents are the carbapenems, sulbactam, colistin, and polymyxin. There are no data documenting an improved outcome if these organisms are treated with a combination regimen (Level II). If ESBL+ Enterobacteriaceae are isolated, then monotherapy with a third-generation cephalosporin should be avoided. The most active agents are the carbapenems (Level II). Adjunctive therapy with an inhaled aminoglycoside or polymyxin for MDR gram-negative pneumonia should be considered, especially in patients who are not improving with systemic therapy (Level III). More studies of this type of therapy are needed. Linezolid is an alternative to vancomycin for the treatment of MRSA VAP and may be preferred on the basis of a subset analysis of two prospective randomized trials (Level II). This agent may also be preferred if patients have renal insufficiency or are receiving other nephrotoxic agents, but more data are needed (Level III). Antibiotic restriction can limit epidemics of infection with specific resistant pathogens. Heterogeneity of antibiotic prescriptions, including formal antibiotic cycling, may be able to reduce the overall frequency of antibiotic resistance. However, the long-term impact of this practice is unknown (Level II).

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For Level of evidence and classes click here.