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]

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

Antimicrobial Therapy

According to the IDSA guidelines the treatment is classified in three categories depending on the risk factors and the likelihood of drug resistance^[1]

No risk factors for drug resistance with an early onset

The following microorganism are treated with the empirical therapy in the table given below.

Streptococcus pneumoniae
Haemophilus influenzae
Methicillin-sensitive Staphylococcus aureus
Antibiotic-sensitive enteric gram-negative bacilli
Escherichia coli
Klebsiella pneumoniae
Enterobacter species
Proteus species
Serratia marcescens

Hospital-acquired pneumonia or ventilator-associated pneumonia in patients with no known risk factors for multidrug-resistant pathogens, early onset, and any disease severity
Preferred Regimen
▸ Ceftriaxone 1-2 g q 24 hr IV or IM (max dose: 4 g/24 hr) OR ▸ Levofloxacin 750 mg every day for 7-14 days OR ▸Moxifloxacin Oral, I.V.: 400 mg every 24 hours for 7-14 days OR ▸Ciprofloxacin I.V.: 400 mg every 8 hours for 10-14 days OR ▸ Ampicillin sulbactam 1-2 g q 6-8 hr IV or IM (max daily dose: 8 g). OR ▸ Ertapenem I.M., I.V. 1 g once daily for 10-14 days

LATE-ONSET DISEASE OR RISK FACTORS FOR MULTIDRUG-RESISTANT PATHOGENS AND ALL DISEASE SEVERITY

The following microorganism are treated with the empirical therapy in the table given below.

Streptococcus pneumoniae
Haemophilus influenzae
Methicillin-sensitivec Staphylococcus aureus
Antibiotic-sensitive enteric gram-negative bacilli
Escherichia coli
Klebsiella pneumoniae
Enterobacter species
Proteus species
Serratia marcescens
MDR pathogens like
1. Pseudomonas aeruginosa or
2. Klebsiella pneumoniae
3. Acinetobacter species
Methicillin-resistant Staphylococcus aureus (MRSA)
Legionella pneumophila

Hospital-Acquired Pneumonia Ventilator-Associated Pneumonia Healthcare-Associated Pneumonia In Patients With Late-Onset Disease Or Risk Factors For Multidrug-Resistant Pathogens And All Disease Severity
Preferred Regimen
▸ Cefepime 1–2 g every 8–12 h OR ▸ Ceftazidime 2 g every 8 h OR ▸Imipenem 500 mg every 6hr / 1g every 8 h OR ▸Meropenem1 g every 8 hr OR ▸ Piperacillin-tazobactam 4.5 g every 6 hr OR ▸ Ciprofloxacin 400 mg every 8 h OR ▸Levofloxacin750 mg every day 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 every 12 hrs OR ▸Vancomycin 15 mg/kg every 12 hrs

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 Q8hrly or Q12 hrly in patients with normal renal funcion 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 ^[2], ^[3], ^[4].

Supportive Trial Data ^[5]

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

Anaerobes

Antimicrobial 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 ^[2]

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)

For Level of evidence and classes click here.

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).