Recommended Diagnostic Strategy

• Combination of the preceding two methods

• Obtain either a quantitative or semiquantitative culture of a lower respiratory sample. Initiate empirical broad-spectrum antibiotic therapy

• Days 2 and 3: Check culture results, and assess clinical response to therapy: temperature, WBCs, chest x-ray, oxygenation, purulent sputum, hemodynamic changes, and organ function

• Assess clinical improvement at 48 to 72 hours:

• Improvement and culture negative—stop antibiotics

• Improvement and culture positive—narrow antibiotic therapy

• No improvement and culture negative—consider other pathogens, complications, or other diagnosis

• No improvement and culture positive—change antibiotic therapy and consider other pathogens, complications, or other diagnosis

Currently there is debate over whether or not double coverage for pseudomonas is required. In vitro studies have shown that aminoglycosides exhibit synergistic k illing against gram-negative bacilli when combined with ^-lactams. Dosing of the aminoglycosides is dependent upon the patient's renal function. A high-dose once-daily regimen (e.g., 4-7 mg/kg gentamicin or tobramycin or 15-20 mg/kg amikacin) can be utilized in patients with good renal function. Most of the studies enrolled patients with estimated creatinine clearances of at least 70 mL/min (1.17 mL/s). Meta-analyses have shown high-dose once-daily regimens to be as efficacious as and less toxic than divided daily dosing.32-36

In addition to obtaining a synergistic effect, another reason for double coverage when treating VAP, HAP, or HCAP is to broaden the coverage empirically to increase the likelihood of covering the majority of resistant pathogens. VAP is the most studied of these types of pneumonias and is often the most severe. Studies have demonstrated an increase in mortality when inadequate therapy is initiated for VAP. Crude mortality ranges from 35% to 92% with inadequate therapy compared to 25% to 47% with adequate therapy.17

Once a pathogen or pathogens have been identified, therapy should be narrowed to cover only those pathogens. Use of broad-spectrum antibiotics for prolonged durations increases the risk of colonization with MDR pathogens.

Table 71-4 CAP Pediatric Dosing

BodyWcigM Ltn Thjn J.OOO-g

Body Wciqhl Greater Thflti 2,-SOOq

BodyWcigM Ltn Thjn J.OOO-g

Body Wciqhl Greater Thflti 2,-SOOq

Pruq tRnuici

□ 7 C>nys Old

7-38 Ctayi Old

«-7 PiiysOIri

7-28 Opyt OM

D«ys Old

Amojildllln (orally)

14 mg/)ig every

17 mgJlu; every

1? Iwuri

SliourS

Anmrtellln-

IS m^kgevety

ITK^kfl fr^fy

45 eveiy

tlavuhnatp (orally}

12 houts

12 hours

12 hours

Celtninirrie JW

50 m<ytQ evtf y

50 rug/ty-eveiy

50 nig/ki evr?i y

50 mg/hywiy

50 rni^ky eveiy

12 hnn;

fthouri

1? hCHjti

a hours

fi hours

CeftrlaaontflMflV)

25 my/hfevery

50 mgAg cwiy

25 my/Kg Cvtry

SO mg/ky <?wi y

iO mg/ky n-wiy

J4 hoyrs

24 hew

¡4ho(JiS

Cefuroudn» (orally

15 my/kg every

12 hours

Ajirhramyrln (ofallyflV)

i mg/hy fy&y

lOmiykO every

5 iKj/ty 4?wty

10 fiKj/kr) ewr y

It) mg/ki] evety

24 hours

24 hours

24 houis

24 hours

24 houts

fl^riihiom^in RXflly)

7,5 m^/ln)

1i hours

Table 71-5 Empirical Therapy for Late-Onset HAP, HCAP, or VAP in Adults

Table 71-5 Empirical Therapy for Late-Onset HAP, HCAP, or VAP in Adults

CrCI1 Grrjlrr Than 50 mL.'mrn

Antibiotic (Rout*)

500 mg every 6 hours oi I g H^yiiuifi 1 r^evety 8 hen*? 4.5y tvtry G liOurt Oi li75y iviiy 4 hotjis

3,1 0ewfy4-t>h«jn 7S0 mg every 21 hows

400 mg every fl hours

5-7 my/hg every 24 hodis

JO mg/kg every 24 hours

1J-J0 mg/1«g pvety li hours

60D mg every 12 hours

Cftl 30-S0(nUmln CrCI 10-lD mL/Uiin

CrCl L*M Tli^n 10 mL/mln

Cciriiifflc Celteidime UVI

Kinpenem (IV)

MiHcJpiiwi (IVl «l^iXLillli I [jJCtitKldrti M

Levolloiuc in liVAr.illy'i

Clpailosadn (IV) ClpiCi|friK.ln (i.ii,illyj GuiMamtln

TotHJmtyii^flV] AmikaclnHIV)

Vancomycin' (M

llnejolid (IViW illy]

1-2 Wly JJIOoi 1-2 g every 12 houia

SdOmgewy 6-Shouu I q every 11 hours 4.5gtvt<y 8 hcwucs

7 ^ Cvtf y 4-6 hoori 750 rrg every 48 hours

4(X) ev«y B houis JW illy CYifyS-IVXiii 1.7-2 my/kg every li-14 houii 7.5 ing/kg every I ¿24 noifli mcy kg evef y 24 hours fOOmgevay 12 hours

I ^fivtry 24 htHUS I-2 g every 12-24 hourt

12 hiWii

4.5 gcwiy 8-12 howl Of 0 every i-lhoun J if fl^cfyi hours 750 mg nl then 500 my flW*y4R hcuis 400 rrg every 12 houis 7SO mg ivtryl2 IWufi 1.7-2 my/kg every

36 hems 7.5 my/kg every

3i hCwi 15-JQ mg/fcgemy 48 hours fiOQ nvg every 12 hours

CL5-I ^MKy 24 hows (-2 g every 24 hours iftO mq every l> hours

W0 mi) houii

4.5 y t\t<y 12 tKuiS Of S.ftSgercyAhauna 2.75 (j PWf (i roidi fvery 12 hoors 750 mg xl I hen 500 mg every 481 Wui^S 400 mgeimy 24 hours /SO rflQ tvtry 24 IWurS f.7-2 m^lfg every 48 houil 7.5 my/kg every hours

IS-30 mtykg every

72 hours fifiO mq every II hours titll, cwtlrJi« I'hii.wi

Trough concenlralions ideally should be nondeieciablp. less than I rnt<ymL iat cjentamicln (AfH litioH) and tobramycin (7.14 lundA) a»vJ

Ins lhan 4 1o 5nicg/hiL (6.84 -6.5S pmol/l}lof ai^kiKinare potenUally acceptable.

1 lrOUf|ll (OfKflHi¿(ioni Should hitiVOCft 15 irxf 20 rlflCy/ml [10 -14 UIKifll/ll.

Duration of Therapy

® The duration of therapy for pneumonia should be kept as short as possible and depends upon several factors: type of pneumonia, inpatient or outpatient status, patient comorbidities, bacteremia/sepsis, and the antibiotic chosen. If the duration of therapy is too prolonged, then it can have a negative impact on the patient's normal flora in the respiratory and GI tracts, vaginal tract of women, and on the skin. This can result in colonization with resistant pathogens, Clostridium difficile colitis, or overgrowth of yeast. In addition, the longer antibiotics are administered, the greater the chance for

toxicity from the agent as well as an increase in cost.

For treating outpatient CAP, two antibiotics are approved for a 5-day duration of therapy, levofloxacin (the 750-mg once daily dose) and azithromycin. The duration of therapy for all other agents used to treat CAP is 7 to 10 days. For treatment of CAP in patients admitted to the hospital, the duration is dependent upon whether or not blood cultures were positive. In the absence of positive blood cultures, the duration of therapy is 7 to 10 days. If blood cultures were positive, the duration of therapy should be 2 weeks from the day blood cultures first became negative.

The duration of therapy cited in the literature for HCAP, HAP, or VAP ranges from 10 to 21 days. Efforts should be made to shorten the duration of therapy from the traditional 14 to 21 days to periods as short as 7 days, provided that the etiologic pathogen is not P. aeruginosa, and that the patient has a good clinical response with resolution of clinical features of infection. Shortening the duration of therapy is acknowledged as beneficial because of the colonization, toxicity, and cost issues. The Clinical Pulmonary Infection Score (CPIS) has been used to determine when to end therapy for VAP. Luna and colleagues used the CPIS and found that patients who survived

VAP and were treated with adequate therapy clinically improved within 3 to 5 days. This study was instrumental in recommending a shortened duration of therapy of 6

days. Another study found that when the CPIS was six or less, those patients were at

low risk of VAP or resistant pathogens and treatment only needed to be for 3 days. outcome evaluation

For CAP, outcomes include preventing hospitalization, shortening the duration of hospitalization, and minimizing mortality. For patients admitted to the hospital, if antibiotics are initiated within 4 hours of presentation, the duration of hospitalization is decreased compared to when antibiotics are started after 4 hours.39

Improvement of symptoms should occur within 48 to 72 hours after initiation of therapy for most patients with CAP. Response to therapy could be slowed in patients with underlying pulmonary disease such as moderate to severe asthma, COPD, or emphysema. In patients not responding to therapy and when there are no underlying factors that would suggest a slowed response to therapy, then other infectious and noninfectious reasons must be considered. The infection could be caused by a patho gen not covered by the initial therapy, a drug-resistant isolate could be present, or more severe infection could be present (nonpulmonary) and the patient should be ree-valuated. Noninfectious reasons to consider include pulmonary embolus, congestive heart failure, carcinoma, lymphoma, intrapulmonary hemorrhage, and certain inflammatory lung diseases.

Outcome parameters for VAP, HAP, and HCAP are similar to those with CAP. Clinical improvement should occur within 48 to 72 hours of the start of therapy. If a patient is not responding to therapy, then, again, consider infectious and noninfectious reasons. Infectious explanations are the same as for CAP, but noninfectious are not. They include atelectasis, acute respiratory distress syndrome (ARDS), pulmonary embolism or hemorrhage, cancer, empyema or lung abscess.

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