nosocomial

For HAP, VAP, and HCAP, clinicians have a wider armamentarium of antibiotic choices to deal with antibiotic-resistant nosocomial pathogens. Initial antibiotic therapy should have broad activity against the most likely pathogens. Inadequate antibiotic therapy and/or a delay in such therapy were identified as important determinants of mortality among ICU patients with a nosocomial infection.

In contrast to the 1995 ATS guidelines, the 2005 ATS-IDSA guidelines (Table 8) have placed greater emphasis on initial broad-spectrum therapy and the risk of MDR organisms. Similar to the guidelines for CAP, the 2005 recommendations for HAP were derived through expert consensus and are not necessarily based on randomized clinical trials. For HAP or VAP with early onset and no risk of MDR pathogens, ceftriaxone or a fluoroquinolone (levofloxacin, moxifloxacin, or ciprofloxacin) or a £-lactam/£-lactamase inhibitor or ertapenem was recommended. For HAP, VAP, or HCAP of late onset with a risk of MDR pathogens, any one of an antipseudomonal cephalosporin, antipseudomonal carbapenem, 6-lactam/ B-lactamase inhibitor, antipseudomonal fluoroquinolone, or aminoglycoside may be used. If MRSA is suspected, vancomycin or linezolid is recommended. For L. pneumophila, a macrolide or fluoroquinolone is preferred. These recent guidelines reflect the rising prevalence of MDR pathogens in the United States, as discussed previously. In Canada, antibiotic therapy should be tailored to the local epidemiology and clinical practice, since the prevalence of MDR pathogens may differ.

Risk factors for the acquisition of MDR organisms causing VAP include duration of ventilation (7 days or more), prior use of antibiotics, and prior use of broad- spectrum antibiotics (third-generation cephalosporins, fluoroquinolones, or imipenem). The risk factors for MDR HAP or VAP identified in the ATS-IDSA guidelines include antibiotic therapy in the preceding 90 days, 5 or more days since admission to hospital, high prevalence of antibiotic resistance in the community or the hospital, and immunosuppression due to disease or therapy. Risk factors for HCAP include a hospital stay of 2 days or more in the preceding 90 days, residence in a long-term care facility, home infusion therapy (including antibiotics), long-term dialysis within 30 days of the infection, home wound care, and exposure to a family member infected with a MDR pathogen. Kamagra Oral Jelly

Table 8. Recommendations of the American Thoracic Society and Infectious Diseases Society of America for Treatment of Hospital-Acquired Pneumonia




Type of Pneumonia




Potential Pathogens




Recommended Therapy


HAP or VAP, early onset
(< 5
days since admission), no risk factors for antibiotic resistance, any
disease severity



Enteric gram-negative bacilli

(Enterobacter

spp
Klebsiella
spp.,
Proteus
spp.,
Serratia
spp.,
Haemophilus
influenzae),

methicillin-sensitive

Staphylococcus aureus,
Streptococcus pneumoniae


.,
Ceftriaxone OR


levofloxacin, moxifloxacin or ciprofloxacin OR


ampicillin-sulbactam OR


ertapenem


HAP or VAP or HCAP, late onset
(> 5
days since admission), risk
factors for antibiotic resistance, any disease severity


Pseudomonas aeruginosa,
Klebsiella pneumoniae,* Acinetobacter

spp.


Antipseudomonal cephalosporin OR


antipseudomonal carbapenem OR


B-lactam/B-lactamase inhibitor OR


antipseudomonal fluoroquinolone OR


aminoglycoside


Methicillin-resistant
S. aureus


Linezolid or vancomycin


Legionella pneumophila


Macrolide or fluoroquinolone

Successful monotherapy of HAP or VAP with antibiotics such as the fluoroquinolones, imipenem, and meropenem has been documented and is supported in the literature. Nonetheless, the respective roles of monotherapy and combination therapy have been actively discussed. Recent meta-analyses have questioned the role of combination therapy for gram- negative and pseudomonal bacteremia and for febrile neutropenia. In one meta-analysis of 64 studies comparing £-lactam monotherapy with a £-lactam- aminoglycoside combination in severe infections, no survival benefit was found with the 6-lactam combination. Monotherapy may decrease costs and minimize antibiotic exposure, which may be helpful in decreasing the risk of MDR pathogens and adverse outcomes. For certain pathogens such as P. aeruginosa, combination therapy may provide broader activity as well as limiting the emergence of antibiotic resistance. The current ATS-IDSA guidelines support the use of monotherapy for HAP and VAP if resistant pathogens are absent; conversely, the guidelines recommend that combination therapy be used when MDR pathogens are suspected, despite limited supportive data. Others have advocated a similar approach; for example, Fagon and Chastre suggested that a £-lactam plus an aminoglycoside or fluoroquinolone be used initially for HAP pending results of microbiologic testing, with monotherapy reserved for when P. aeruginosa and other MDR pathogens have been excluded. Nevertheless, antibiotic therapy should be tailored to local epidemiology, prevalence of antibiotic- resistant pathogens, risk factors, severity of illness, and culture and sensitivities.
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The recommended duration of therapy for HAP and VAP ranges from 7 to 21 days, although the optimal duration has not been established. A consensus conference on VAP management suggested that therapy be continued for at least 72 h after clinical response, with some clinical improvement expected at about 48 to 72 h of therapy. However, antibiotic treatment beyond 14 days may promote colonization with P. aeruginosa or other Enterobacteriaceae. De-escalation (also known as streamlining or narrowing) of antibiotic therapy on the basis of culture results, susceptibility, and clinical response is encouraged. Therapy may be limited to 7 days if there is a clinical response and P. aeruginosa is absent.

Table 9. Clinical Pulmonary Infection Score (CPIS)*t




Temperature (°C)



> 36.5


and


< 38.4


0



> 38.5


and


< 38.9

1



> 39


and


< 36


2




Blood leukocytes, mL
-1



> 4000


and


< 11 000


0



< 4000

or


> 11 000

1



+


band forms


> 50%

1




Tracheal secretions


Absent


0


Present (nonpurulent)

1


Present (purulent)


2




Oxygenation (Pa
o2/FIo2),
mm Hg



> 240

or
ARDS


0



< 240


and no ARDS


2




Pulmonary radiography


No infiltrate


0


Diffuse (or patchy) infiltrate

1


Localized infiltrate


2




Progression of pulmonary infiltrate


No radiographic progression


0


Radiographic progression


(after CHF and ARDS excluded)


2




Culture of tracheal aspirate


Pathogenic bacteria (predominant
organism) rare


or light in quantity or no growth


0


Pathogenic bacteria moderate or heavy
in quantity

1


Same pathogenic bacteria as seen on
Gram staining

1

To reduce costs in the ICU and to address the overuse of antibiotics (and hence minimize the emergence of antibiotic-resistant pathogens in this setting), shorter courses of antibiotic therapy have been suggested. In a recent trial, which compared 8 and 15 days of antibiotic treatment for VAP, Chastre and others found that mortality rate, rate of recurrence, length of ICU stay, number of days without mechanical ventilation, and number of days of organ failure were similar for the 2 treatment arms. Although the outcomes were similar, VAP patients with nonfermenting gram- negative rods (e.g., P. aeruginosa) had higher recurrence and relapse rates with the shorter treatment course. Further investigations are required to define the role of shorter courses of antibiotic treatment in patients with HAP and VAP.
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Using a clinical prognostic scoring system (Table 9), Singh and others found that outcome was similar for patients with VAP who received shorter and longer courses of antibiotic treatment in a nonblinded study. The clinical pulmonary infection score (CPIS), developed by Pugin and others, uses 6 clinical variables to determine the presence or absence of pneumonia. Singh and others found that in patients with a low CPIS score (6 or less) on initiation of antibiotics, therapy could be discontinued at 3 days if the CPIS score remained at 6 or less. Similarly, the ATS-IDSA guidelines suggested that a CPIS of 6 or less for 3 days could be used as a criterion for discontinuing therapy in patients at low risk of pneumonia, although further validation is required for severe VAP.