Combination therapy with macrolides improves mortality in sepsis even if pt doesn’t have atypicals (Intens Care Med 2010;36:612)
Chest. 2006;130:16-21.) Antibiotic Timing and Diagnostic Uncertainty in Medicare Patients With Pneumonia
Cultures do not change management (Ann Emerg Med 2005;46(5):393)
Only high PORT grade pneumonias should get cultures (Resp Med 2001;95:78)
also Intens Care Med 1995;21:24; Chest 1994;105:1487
RCT of pathogen driven vs. broad spectrum rx (THorax 2005;60:672)
Multi-centre trial is the coffin nail in the ridiculous CMS debacle (Acad Emerg Med 2011;18:496) No assoc between the measure and mortality
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Consider PE, HIV
Sputum gram stain
can be useful to expand not narrow antibiotic coverage,
sputum culture is virtually worthless to narrow
Should have <10 Squamous Epith Cells (SEC) per LPF and >25 PMNs
> 10 diplococci are enough for strep pneumo
legionella antigen can be detected in the urine.
The role is still uncertain. It may be useful to diagnose such entities as aspergilliosis in COPDers on chronic steroids for example.
Get Base deficit
Immediate ET suction after intubation was as good as BAL or protected brush or plugged telescoping catheter (Chest 2006;130:956)
BAL quant vs. endotracheal aspiration showed no diff in outcome or overall use of abx (740 pt NEJM 2006;355:2619)
However, only 10% of blood cultures in pneumonia are positive, and less than 10% of the positive results mandate a change in therapy. Considering that some patients die within 24 hours and that cultures do not reveal the number of mixed infections, less than 1% of blood cultures will actually have an impact on treatment. A study of 517 patients with community-acquired pneumonia (CAP) at Emory showed that only 7/517 had management changed by culture result (12). A study of 93 cases of severe CAP in a German hospital could not demonstrate any impact at all of blood cultures (13). Of 939 pediatric patients with pneumonia at the University of Pittsburgh, not one had a treatment change from blood cultures (14). At a minimum charge of $100 for a set of blood cultures, it might cost in the range of $10,000 to get one treatment-altering result. The PORT study found lower in-patient mortality in patients who had blood cultures drawn, but this did not change when the blood cultures were drawn post-treatment, suggesting that blood cultures may have been a surrogate marker for an overall more aggressive approach to management. 12.Chalasani. Clinical Utility of Blood Cultures in Adult Patients with Community-Acquired Pneumonia with Defined Underlying Risks. Chest. 1995; 108: 932 13.Ewig. Value of Microbial Investigation in Community-Acquired Pneumonia Treated in a Tertiary Care Center. Respiration. 1996; 63: 164 14.Hickey. Utility of Blood Cultures in Pediatric Patients Found to Have Pneumonia in the Emergency Department. Ann Emerg Med. 1996; 27: 721
Blood cultures rarely altered therapy for patients presenting to the ED with pneumonia. More discriminatory blood culture use may potentially reduce resource utilization. (Annals of Emergency Medicine Volume 46, Issue 5 , November 2005, Pages 393-400)
a) only positive in 4-12% of cases (including false-positives); b) completely miss and under-represent an important subset of CAP cases (chlamydia, mycoplasma, and legionella); c) resistant S. pneumonia is less likely to produce bacteremia (Chest 2001; 119: 5-7) and relying on BCx would under-represent its prevalence; d) in vitro susceptibility results do not directly correlate with the predicted in vivo efficacy of antibiotics, calling into question the clinical utility of susceptibility testing on the few positive BCx results that are obtained (Intensive Care Med 1995; 21: 24-31; Clin Infect Dis 1998; 26: 1-10; Chest 1999; 116: 535-538).
Limited yield, minimum impact (Chest 121:1486, 2002)
Get IgM or IgG
Send urinary antigen
Physical examination Physical examination reveals rales with subsequent signs of consolidation. Fever is virtually always present and oral temperature greater than 40ºC should suggest the possibility of Legionnaires’ disease. Bradycardia relative to temperature elevation has been found in elderly patients with more severe pneumonia . Miscellaneous findings include: disseminated intravascular coagulation, glomerulitis, rhabdomyolysis, various rashes, and neuropathies; these may be nonspecific findings related to the severity of infection, underlying disease, or perhaps side-effects of drug therapies.
Urinary test (Spec 90%, Sens 50-80%)
Physical Exam for Dx Pneumonia
Ann Emerg Med 18(1):13 Jan 1989
Metlay JP, Kapoor WN, Fine MJ. Does this patient have community-acquired pneumonia? Diagnosing pneumonia by history and physical examination. JAMA 1997;278:1440-1445. [Abstract] Wipf JE, Lipsky BA, Hirschmann JV, et al. Diagnosing pneumonia by physical examination: relevant or relic? Arch Intern Med 1999;159:1082-1087.
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Community Acquired Pneumonia (CAP)
Must Cover these 6 for all CAP
Typical AtypicalS. Pneumo Legionella H. Flu Chlamydia M. Catarrhalis Mycoplasma
COPD, ETOH, Diabetics
IVDA, small infiltrates, necrotizing
ETOH, necrotizing, currant jelly sputum
can do urine testing
ICU patients, particularly those with structural lung disease, on ventilators, or steroid-dependent nursing home patients, need aminoglycoside coverage for pseudomonas. Pseudomonas may be seen as source of CAP in steroid dependant and structural lung disease patients. Ideally double therapy would be used to cover to prevent the emergence of resistance during treatment.Back to top
Aspiration Pneumonia and Pneumonitis
BACTERIOLOGY Despite extensive investigations, the diagnosis of the bacterial cause of CAP is made in 50% or less of patients overall; this is particularly so in the elderly, who may not be able to produce adequate sputum specimens for evaluation. 88, 89 Oropharyngeal colonization with gram-negative pathogens and S. aureus with subsequent aspiration accounts for the greater prevalence of these pathogens in elderly patients with CAP. It is unclear, however, if patients with dysphagia are at an increased risk of developing pneumococcal pneumonia, because no study has specifically reported the microbiology of CAP in patients with oropharyngeal dysphagia and aspiration. However, Kikuchi and colleagues reported a high incidence of silent aspiration in otherwise healthy elderly ambulatory patients with no specific risk factors for gram-negative or S. aureus oropharyngeal colonization who developed CAP. 47 Unfortunately, in this study the microbial causes of CAP were not reported. A number of studies performed in the early 1970s investigated the bacteriology of community-acquired “aspiration pneumonia.” 87,90-92 Bacteriologic specimens were obtained by percutaneous transtracheal sampling and/or thoracocentesis. In all these studies anaerobic organisms were the predominant pathogens, isolated alone or together with aerobes. Based on these studies, antibiotics with anaerobic activity have became “the standard of care” for patients with aspiration pneumonia. 2, 93 However, it is important to recognize that in all these studies the microbiologic specimens were obtained after a significant delay and frequently after complications such as abscesses, necrotizing pneumonia, or empyema had developed. Furthermore, many of the patients were chronic alcoholics, had been symptomatic for up to 90 days, and complained of having a putrid sputum. These patients are clearly distinct from the typical patients seen today with acute aspiration pneumonia. Furthermore, it is possible that the organisms recovered by transtracheal aspiration represent oropharyngeal flora that contaminated the trachea during the procedure (due to aspiration) or bacteria that colonized the trachea, rather than representing true pulmonary pathogens. This postulate is supported by Moser and colleagues, who demonstrated discrepancies between bacteria recovered by transtracheal aspiration and by transthoracic needle aspiration in dogs with experimental pneumonia. 94 Recently, two studies have been reported in which invasive lower respiratory tract sampling (protected specimen brush) together with quantitative and anaerobic culture techniques were performed in the patients with acute aspiration syndromes. 95, 96 Mier and colleagues studied 52 patients admitted to an ICU with “aspiration pneumonia.” 95 Bacterial pathogens were isolated in significant concentrations (103 colony-forming units/mL) in only 19 patients, the spectrum of organism being determined by whether the aspiration was community or hospital acquired, with S. pneumoniae, S. aureus, H. influenzae, and Enterobacteriaceae predominant in patients with community-acquired aspiration and gram-negative organisms, including Pseudomonas aeruginosa in patients with hospital-acquired aspiration. No anaerobic organism was isolated in any of the patients. In a similar study, we performed blind protected specimen brush sampling in 25 patients with gastric aspiration. 96 Bacterial pathogens were isolated in 12 patients. Risk factors for gastric colonization were present in 8 of the 12 patients (small bowel obstruction/ileus, tube feeding, H 2 blockers). The spectrum of pathogens was similar to that reported by Meir and colleagues. 95 Furthermore, we did not isolate any pathogenic anaerobic organisms. MANAGEMENT Antimicrobial therapy is unequivocally indicated in patients with aspiration pneumonia. The choice of antibiotics should depend on the setting in which the aspiration occurs (home, nursing home, or hospital) as well as on the patient’s premorbid condition. However, antimicrobial agents with gram-negative activity such as fluoroquinolones, third-generation cephalosporins, piperacillin, or a carbapenem are usually required. Penicillin and clindamycin, the “standard” antimicrobial agents for aspiration pneumonia, provide inadequate activity in the majority of patients with aspiration pneumonia. 95 Antimicrobials with specific anaerobic activity are not routinely warranted and may be indicated only in patients with severe periodontal disease, patients expectorating putrid sputum, and patients with a necrotizing pneumonia or lung abscess on chest radiograph. 95, 96 All elderly patients with CAP and all patients with aspiration pneumonia require consultation by a speech and language pathologist to assess for the presence of dysphagia. Assessment of the cough and gag reflex is unreliable in screening for patients at risk of aspiration; a comprehensive swallowing evaluation performed by a specialized speech-language pathologist is, therefore, required. The speech-language pathologist can reliably identify those patients who aspirate by performing a bedside swallowing evaluation supplemented by either a videofluoroscopic swallow study or a fiberoptic endoscopic evaluation. 97-99 This evaluation identifies those patients who require further behavioral, dietary, and medical management to reduce the risk of aspiration. ( Criticalcaretext.com) 95. Mier L, Dreyfuss D, Darchy B, et al: Is penicillin G an adequate initial treatment for aspiration pneumonia? A prospective evaluation using a protected specimen brush and quantitative cultures. Intensive Care Med 1993;19:279-284. Medline Similar articles 96. Marik PE, Careau P: The role of anaerobes in patients with ventilator-associated pneumonia and aspiration pneumonia: A prospective study. Chest 1999;115:178-183. Medline Similar articles
Great review in (crit care med 2011;39:818)
In severe CAP, most common etiology is strep, and then surprisingly, it is legionella (Parrillo)
splenic dysfunction-pneumococcus and h. flu
neutropenia-gram neg bacilli
exposure to farm animals and pregnant cats-coxiella burnetti (Q fever)
exposure to mouse droppings-Hantavirus
Non-Hospital Acquired Pneumonia (Pharm Ther 1999, 24: 390-396)
S. Aureus 13%
S Marcescens 10%
E. Coli 1.5%
Hospital Acquired Pneumonia ((Pharm Ther 1999, 24: 390-396)
S. Aureus 14.6%
E. Coli 6.4
Farm Animals or Pregnant Cats-coxiella burnetti (Q Fever)
Bat or Bird Droppings-histoplasma capsulatum
Southwest US-Coccidioides immitus
Southeast and Eastern Asia-burkholderia pseudomallei, avian flu, SARS
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NEJM 2001;344:665Back to top
Chemical Pneumonitis-no ABX
Look at total lymphocytes, if less than 1000, assume low CD4.
Vanco penetrates poorly into lung; use with rifampicin instead or just use linezolid.
Most common in Ohio and Mississippi River Valleys
Inhalation of spores can cause fever, HA, cough, dyspnea, chest pain, myalgia c X-Ray findings of of patchy parenchymal opacities c hiliar or mediastinal adenopathy.
Especially risky behavior involves anything with bird or bat feces containing soil.
Chronic pulmonary histo can occur in pts c prior lung disease or AIDS players.
Dx c culture, serum antibodies.
Treatment-most do not need treatment. If severe, Ampho B, then switch to azole
Southwest US, especially AIDS
Sx same as above
Dx c IgG
Ohio and Mississippi River Valleys and Great Lakes
Mass-like opacities can resemble malignancies
Dx by visualization of the yeast in sputum samples
Rx Ampho B
Neutropenia or AIDS
Fever cough and chest pain
Diffuse infiltrates or nodular opacities (peripherally located wedge shaped opacity)
Mold from bread
Surgical Resection of diseased tissue and Ampho B
Especially from bird droppings
Can cause meningitis in AIDS, but lung is entry site, so can cause pneumonia
Fever, malaise, chest pain. Often confused c PCP pneumonia.
Antigen titers in blood or CSF excellent test.
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early antibiotics (<4 hours) improves outcomes (Arch Intern Med 2004 Mar 22)
Clindamycin/Aztreonam for severe pneumonia in PCN allergic nosocomial.
Mechanically ventilated patients often have polymicrobial infections
Parapneumonic effusions >10 mm should be tapped
DX: good sputum=<5 epithelial, >25 WBC
Pneumonia in HIV, keep in TB isolation until proven negative
Zithromax as effective as Cefuroxime and Erythomycin (Arch Int Med 2000;160:1294-1300)
zithromax or biaxin (alt. Fluroquinolones)
Ceftriaxone and Zithromax IV for most patients
Mild pneumonia can get zithro alone
increased risk of gram negative (kleb) such as etoh:
ceft + zithro
increased risk of pseudomonas
Zosyn, cefepime, imipenem, meropenem
cipro or levo (750) or (amino and zithromax)
pcn allergy: aztreonam plus amino plus either macrolide or fluorquinolone
Aspiration or Anaerobic
ceft + zith + clinda (alt: levo/clinda or b-lactam/lactamase inhibitor)
Severe pneumococcal disease
mortaility benefit from Dual effective therapy (DET) over SET (Arch Internal Medicine 2001:161)
probably best choice is ceft + moxi or levo
(alt: ceft, cefepime, zith or imi + zith + aminoglycoside)
(cefipime or zosyn) + (levo or zith) + vanco
Moxiflox-lowest MIC against s. Pneumo, prolonged QT
Gatiflox-can also prolong QT
Levoflox-not great psuedomonal coverage
do early abx help one says no (
Silber, S.H., et al, Chest 124(5):1798, November 2003
), everyone else says yesBack to top
Sat <90% or PORT Criteria
Class 1: Mortality 0.1 to 0.4
Class 2: 0.6 to 0.7
Class 3: 0.9 to 2.8
4 of the 7 deaths in these 3 groups were pneumonia related.
Port Study (NEJM, 336:243-250, 1997)
SITE OF TREATMENT
THE INITIAL SITE OF TREATMENT SHOULD BE BASED ON A THREE-STEP PROCESS: (1) ASSESSMENT OF PREEXISTING CONDITIONS THAT COMPROMISE SAFETY OF HOME CARE; (2) CALCULATION OF THE PNEUMONIA PORT (PNEUMONIA OUTCOME
RESEARCH TEAM) SEVERITY INDEX (PSI) WITH RECOMMENDATION FOR HOME CARE FOR RISK CLASSES I, II AND III; AND (3) CLINICAL JUDGMENT (A-II). (IDSA 2003)
0-1 consider outpt, 0 factors=0.7% and 1 factor=2.1%
2 or more gets admitted
3 or more should get ICU care
American Journal of Respiratory and Critical Care Medicine Vol 174. pp. 1249-1256, (2006) In the multivariate analyses, eight independent predictive factors were correlated with severe community-acquired pneumonia: arterial pH < 7.30, systolic blood pressure < 90 mm Hg, respiratory rate > 30 breaths/min, altered mental status, blood urea nitrogen > 30 mg/dl, oxygen arterial pressure < 54 mm Hg or ratio of arterial oxygen tension to fraction of inspired oxygen < 250 mm Hg, age 80 yr, and multilobar/bilateral lung affectation. From the parameter obtained in the multivariate model, a score was assigned to each predictive variable. The model shows an area under the curve of 0.92. This rule proved better at identifying patients evolving toward severe community-acquired pneumonia than either the modified American Thoracic Society rule, the British Thoracic Society’s CURB-65, or the Pneumonia Severity Index. Conclusions: A simple score using clinical data available at the time of the emergency department visit provides a practical diagnostic decision aid, and predicts the development of severe community-acquired pneumonia.Back to top
ASCAP 2003 Recommendations
Must cover strep pneumo, h. flu, m. catarrhalis, m. pneumoniae, c. pneumoniae, legionella pneumophilia
Numerous studies show that atypicals are pathogens either on their own or tagging along with typical bacteria (Thorax 1996, 51:179, Arch Intern Med 1997, 157:1709, Thorax 1996, 51:185)
Ceftriaxone can be given once a day, cefotax must be given Q8
Clinical exam is not sufficient to dx typical vs. atypical.
symptoms can last months after treatment
JCAHO demands ABX within 8 hours, HCFA says within 4 (<4 improves mortality)
2 drugs better in if severe s. pneumo infection (Arch Intern Med 2001, 161:1837)
moxiflox more effective than other quinolones as it has a more favorable MIC against s. pneumo
if pt on fluroquinolone in past 3 months, may not be the best choice.
If worried about gram negative anaerobes, add aztreonam or gentamycin
Combine them with 3rd gen antipseudomonal PCN, extended spectrum quinilone, Monobactum, Extended Cephalosporin
In the elderly, always consider kleb, e.coli, pseudomonas, DRSP
Broaden coverage if the patient is:
>85 y/o, NH acquired, Aspiration, ETOH (klebsiella), RX failure in past or present, Prior recent hospitalizations, prior icu admit for pneumonia, high community resistance to s. pneumo, immunodeficient patient.
If using oral zithro as IV step-down agent, give 500 mg a day for 10 days total course.
Ceftriaxone without macrolide is an independent mortality factor (ASCAP ref. 145)
ICU players: ceft+fluroquinolone+flagyl/Clinda or use Unasyn instead of ceft.
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Risk increases 1% with each day of mech vent during the 1st month.
Enteric gram negatives are scarce in healthy patients but colonize the nasopharynx in 35% of ill pts and 75% of critically ill patients.
Staph Aureus is also a common nosocomial player
Feeding tubes placed in the jejunum instead of the stomach may decrease the possibility of nosocomial pneumonia.
Most recent guidelines are by ATS and IDSA (Am J Resp Crit Care Med 2005;171:388-416)
HCAP is now considered nosocomial
Nosocomial pneumonia is associated with MDR pathogens
Pseudomonas, Klebisella, and Acinetobacter are gram negs
S. Aureus is majority of Gram Positives
Anaerobic infections are rare
lower tract samples should be obtained
Initial empiric antibiotic therapy for hospital-acquired pneumonia or ventilator-associated pneumonia in patients with no known risk factors for multidrug-resistant pathogens, early onset, and any disease severity
Potential Pathogen Recommended Antibiotic* Streptococcus pneumoniae Ceftriaxone Haemophilus influenzae or Methicillin-sensitive Staphylococcus aureus Levofloxacin, moxifloxacin, or ciprofloxacin Antibiotic-sensitive enteric gram-negative bacilli or Escherichia coli Ampicillin/sulbactam Klebsiella pneumoniae or Enterobacter species Ertapenem Proteus species Serratia marcescens
Initial empiric therapy for hospital-acquired pneumonia, ventilator-associated pneumonia, and healthcare-associated pneumonia in patients with late-onset disease or risk factors for multidrug-resistant pathogens and all disease severity
Potential Pathogens Combination Antibiotic Therapy* Pathogens listed in Table 3 and MDR pathogens Antipseudomonal cephalosporin (cefepime, ceftazidime) Pseudomonas aeruginosa or Klebsiella pneumoniae (ESBL+) Antipseudomonal carbepenem Acinetobacter species (imipenem or meropenem) or ß-Lactam/ß-lactamase inhibitor (piperacillintazobactam)plus Antipseudomonal fluoroquinolone (ciprofloxacin or levofloxacin) or Aminoglycoside (amikacin, gentamicin, or tobramycin) plus Methicillin-resistant Staphylococcus aureus (MRSA) Linezolid or vancomycin Legionella pneumophila
*See Table 5 for adequate initial dosing of antibiotics. Initial antibiotic therapy should be adjusted or streamlined on the basis of microbiologic data and clinical response to therapy.
If an ESBL+ strain, such as K. pneumoniae, or an Acinetobacter species is suspected, a carbepenem is a reliable choice. If L. pneumophila is suspected, the combination antibiotic regimen should include a macolide (e.g., azithromycin) or a fluoroquinolone (e.g., ciprofloxacin or levofloxacin) should be used rather than an aminoglycoside.
If MRSA risk factors are present or there is a high incidence locally.
Initial intravenous, adult doses of antibiotics for empiric therapy of hospital-acquired pneumonia, including ventilator-associated pneumonia, and healthcare-associated pneumonia in patients with late-onset disease or risk factors for multidrug-resistant pathogens
Antibiotic Dosage* Antipseudomonal cephalosporin Cefepime 12 g every 812 h Ceftazidime 2 g every 8 h Carbepenems Imipenem 500 mg every 6 h or 1 g every 8 h Meropenem 1 g every 8 h ß-Lactam/ß-lactamase inhibitor Piperacillintazobactam 4.5 g every 6 h Aminoglycosides Gentamicin 7 mg/kg per d Tobramycin 7 mg/kg per d Amikacin 20 mg/kg per d Antipseudomonal quinolones Levofloxacin 750 mg every d Ciprofloxacin 400 mg every 8 h Vancomycin 15 mg/kg every 12 h Linezolid 600 mg every 12 h
* Dosages are based on normal renal and hepatic function.
Trough levels for gentamicin and tobramycin should be less than 1 µg/ml, and for amikacin they should be less than 45 µg/ml.
Trough levels for vancomycin should be 1520 µg/ml.
VAP state of the art review (Am J Respir Crit Care 2002;165:867)
HCAP is included in the spectrum of HAP and VAP, and patients with HCAP need therapy for MDR pathogens. A lower respiratory tract culture needs to be collected from all patients before antibiotic therapy, but collection of cultures should not delay the initiation of therapy in critically ill patients. Either semiquantitative or quantitative culture data can be used for the management of patients with HAP. Lower respiratory tract cultures can be obtained bronchoAmerican Thoracic Society Documents 389 scopically or nonbronchoscopically, and can be cultured quantitatively or semiquantitatively. Quantitative cultures increase specificity of the diagnosis of HAP without deleterious consequences, and the specific quantitative technique should be chosen on the basis of local expertise and experience. Negative lower respiratory tract cultures can be used to stop antibiotic therapy in a patient who has had cultures obtained in the absence of an antibiotic change in the past 72 hours. Early, appropriate, broad-spectrum, antibiotic therapy should be prescribed with adequate doses to optimize antimicrobial efficacy. An empiric therapy regimen should include agents that are from a different antibiotic class than the patient has recently received. Combination therapy for a specific pathogen should be used judiciously in the therapy of HAP, and consideration should be given to short-duration (5 days) aminoglycoside therapy, when used in combination with a -lactam to treat P. aeruginosa pneumonia. Linezolid is an alternative to vancomycin, and unconfirmed, preliminary data suggest it may have an advantage for proven VAP due to methicillin-resistant S. aureus. Colistin should be considered as therapy for patients with VAP due to a carbapenem-resistant Acinetobacter species. Aerosolized antibiotics may have value as adjunctive therapy in patients with VAP due to some MDR pathogens. De-escalation of antibiotics should be considered once data are available on the results of lower respiratory tract cultures and the patients clinical response. A shorter duration of antibiotic therapy (7 to 8 days) is recommended for patients with uncomplicated HAP, VAP, or HCAP who have received initially appropriate therapy and have had a good clinical response, with no evidence of infection with nonfermenting gram-negative bacilli.
Pseudomonas aeruginosa. P. aeruginosa, the most common MDR gram-negative bacterial pathogen causing HAP/VAP, has intrinsic resistance to many antimicrobial agents (4446). This resistance is mediated by multiple efflux pumps, which may be expressed all the time or may be upregulated by mutation (47). Resistance to piperacillin, ceftazidime, cefepime, other oxyimino- -lactams, imipenem and meropenem, aminoglycosides, or fluoroquinolones is increasing in the United States (16). Decreased expression of an outer membrane porin channel (OprD) can cause resistance to both imipenem and meropenem or, depending on the alteration in OprD, specific resistance to imipenem, but not other -lactams (48). At present, some MDR isolates of P. aeruginosa are susceptible only to polymyxin B. Although currently uncommon in the United States, there is concern about the acquisition of plasmid-mediated metallo- -lactamases active against carbapenems and antipseudomonal penicillins and cephalosporins (49). The first such enzyme, IMP-1, appeared in Japan in 1991 and spread among P. aeruginosa and Serratia marcescens, and then to other gram-negative pathogens. Resistant strains of P. aeruginosa with IMP-type enzymes and other carbapenemases have been reported from additional countries in the Far East, Europe, Canada, Brazil, and recently in the United States (50). Klebsiella, Enterobacter, and Serratia species. Klebsiella species are intrinsically resistant to ampicillin and other aminopenicillins and can acquire resistance to cephalosporins and aztreonam by the production of extended-spectrum -lactamases (ESBLs) (51). Plasmids encoding ESBLs often carry resistance to aminoglycosides and other drugs, but ESBL-producing strains remain susceptible to carbapenems. Five to 10% of oxyimino- -lactam-resistant K. pneumoniae do not produce an ESBL, but rather a plasmid-mediated AmpC-type enzyme (52). Such strains usually are carbapenem susceptible, but may become resistant by loss of an outer membrane porin (53). Enterobacter species have a chromosomal AmpC -lactamase that is inducible and also easily expressed at a high level by mutation with consequent resistance to oxyimino- -lactams and -methoxy- -lactams, 392 AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE VOL 171 2005 such as cefoxitin and cefotetan, but continued susceptibility to carbapenems. Citrobacter and Serratia species have the same inducible AmpC -lactamase and the same potential for resistance development. Although the AmpC enzyme of E. coli is not inducible, it can occasionally be hyperexpressed. Plasmidmediated resistance, such as ESBL production, is a more common mechanism for -lactam resistance in nosocomial isolates, and is increasingly recognized not only in isolates of K. pneumoniae and E. coli, but also Enterobacter species (54). Acinetobacter species, Stenotrophomonas maltophilia, and Burkholderia cepacia. Although generally less virulent than P. aeruginosa, Acinetobacter species have nonetheless become problem pathogens because of increasing resistance to commonly used antimicrobial agents (55). More than 85% of isolates are susceptible to carbapenems, but resistance is increasing due either to IMP-type metalloenzymes or carbapenemases of the OXA type (49). An alternative for therapy is sulbactam, usually employed as an enzyme inhibitor, but with direct antibacterial activity against Acinetobacter species (56). S. maltophilia, which shares with B. cepacia a tendency to colonize the respiratory tract rather than cause invasive disease, is uniformly resistant to carbapenems, because of a ubiquitous metallo- -lactamase. S. maltophilia and B. cepacia are most likely to be susceptible to trimethoprimsulfamethoxazole, ticarcillinclavulanate, or a fluoroquinolone (55). B. cepacia is also usually susceptible to ceftazidime and carbapenems. Methicillin-resistant Staphylococcus aureus. In the United States, more than 50% of the ICU infections caused by S. aureus are with methicillin-resistant organisms (16, 33).MRSA produces a penicillin-binding protein with reduced affinity for -lactam antibiotics that is encoded by the mecA gene, which is carried by one of a family of four mobile genetic elements (57, 58). Strains with mecA are resistant to all commercially available -lactams and many other antistaphylococcal drugs, with considerable country-to-country variability (59, 60). Although vancomycin-intermediate S. aureus,with aminimal inhibitory concentration (MIC) of 816 g/ml, and high-level vancomycin- resistant S. aureus, with an MIC of 321,024 g/ml or more, have been isolated from clinical specimens, none to date have caused respiratory tract infection and all have been sensitive to linezolid (61, 62). Unfortunately, linezolid resistance has emerged in S. aureus, but is currently rare (63). Streptococcus pneumoniae and Haemophilus influenzae. S. pneumoniae and H. influenzae cause early-onset HAP in patients without other risk factors, are uncommon in late-onset infection, and frequently are community acquired. At present, many strains of S. pneumoniae are penicillin resistant due to altered penicillin-binding proteins. Some such strains are resistant as well to cephalosporins, macrolides, tetracyclines, and clindamycin (64). Despite low and moderate levels of resistance to penicillins and cephalosporins in vitro, clinical outcomes in patients with pneumococcal pneumonia and bacteremia treated with these agents have been satisfactory (65). All of the multidrug- resistant strains in the United States are currently sensitive to vancomycin or linezolid, and most remain sensitive to broadspectrum quinolones. Resistance of H. influenzae to antibiotics other than penicillin and ampicillin is sufficiently rare so as not to present a problem in therapy. Legionella pneumophila. The evidence for Legionella pneumophila as a cause of HAP is variable, but is increased in immunocompromised patients, such as organ transplant recipients or patients with HIV disease, as well as those with diabetes mellitus, underlying lung disease, or end-stage renal disease (29, 6669). HAP due to Legionella species is more common in hospitals where the organism is present in the hospital water supply or where there is ongoing construction (3, 29, 6669). Because detection is based on the widespread use of Legionella urinary antigen, rather than culture for Legionella, disease due to serogroups other than serogroup 1 may be underdiagnosed. Detailed strategies for prevention of Legionella infections and eradication procedures for Legionella species in cooling towers and the hospital water supply are outlined in the CDC/HICPAC Guidelines for Preventing Health-careassociated Pneumonia (3). Fungal pathogens. Nosocomial pneumonia due to fungi, such as Candida species and Aspergillus fumigatus,may occur in organ transplant or immunocompromised, neutropenic patients, but is uncommon in immunocompetent patients (7075). Nosocomial Aspergillus species infections suggest possible airborne transmission by spores, and may be associated with an environmental source such as contaminated air ducts or hospital construction. By comparison, isolation of Candida albicans and other Candida species from endotracheal aspirates is common, but usually represents colonization of the airways, rather than pneumonia in immunocompetent patients, and rarely requires treatment with antifungal therapy (70). Viral pathogens. The incidence of HAP and VAP due to viruses is also low in immunocompetent hosts. Outbreaks of HAP, VAP, and HCAP due to viruses, such as influenza, parainfluenza, adenovirus, measles, and respiratory syncytial virus have been reported and are usually seasonal. Influenza, pararinfluenza, adenovirus, and respiratory syncytial virus account for 70% of the nosocomial viral cases of HAP,VAP, and HCAP(3, 7678). Respiratory syncytial virus outbreaks of bronchiolitis and pneumonia are more common in childrens wards and rare in immunocompetent adults (76). Diagnosis of these viral infections is often made by rapid antigen testing and viral culture or serologic assays. Influenza A is probably the most common viral cause of HAP and HCAP in adult patients. Pneumonia in patients with influenza A or B may be due to the virus, to secondary bacterial infection, or both. Influenza is transmitted directly from person to person when infected persons sneeze, cough, or talk or indirectly by personfomiteperson transmission (3, 7981). The use of influenza vaccine along with prophylaxis and early antiviral therapy among at-risk healthcare workers and high-risk patients with amantadine, rimantadine, or one of the neuraminidase inhibitors (oseltamivir and zanamivir) dramatically reduces the spread of influenza within hospital and healthcare facilities (3, 8190). Amantadine and rimantadine are effective only for treatment and prophylaxis against influenzaAstrains, whereas neuraminidase inhibitors are effective against both influenza A and B.
RISK FACTORS FOR MULTIDRUG-RESISTANT PATHOGENS CAUSING HOSPITAL-ACQUIRED PNEUMONIA, HEALTHCARE-ASSOCIATED PNEUMONIA, AND VENTILATOR-ASSOCIATED PNEUMONIA
Antimicrobial therapy in preceding 90 d Current hospitalization of 5 d or more High frequency of antibiotic resistance in the community or in the specific hospital unit Presence of risk factors for HCAP:
- Hospitalization for 2 d or more in the preceding 90 d
- Residence in a nursing home or extended care facility
- Home infusion therapy (including antibiotics)
- Chronic dialysis within 30 d
- Home wound care
- Family member with multidrug-resistant pathogen
Immunosuppressive disease and/or therapyBack to top
nutritional support, ideally with jejunal small bore feeding tube aids in the prevention and treatment of pneumonia.
Clinical Pulmonary Infection Score
The Futility of the Clinical Pulmonary Infection Score in Trauma Patients Introduction: The Clinical Pulmonary Infection Score (CPIS) has received much attention recently. Advocates have touted its use for the diagnosis and duration of therapy in patients with ventilator-associated pneumonia (VAP). However, little has been written about its utility in trauma patients. The clinical, physiologic, and radiologic components of the CPIS may be difficult to differentiate from the systemic effects of injury. Quantitative cultures of the lower airway have been shown to be efficacious in differentiating VAP from the systemic inflammatory response syndrome (SIRS). In this study, we evaluated the potential use of CPIS as the sole means for diagnosis of VAP in critically injured patients. Methods: Patients were identified from the VAP database maintained in our Level I trauma center. Only those who had CPIS calculated at the time of bronchoscopy with BAL were included. VAP required >=105 colonies/mL on quantitative BAL for diagnosis. Antibiotic therapy was based on quantitative BAL results. Patients with <105 colonies/mL were diagnosed with SIRS. Sensitivity and specificity of a CPIS >6 for VAP diagnosis (confirmed by BAL) were calculated. Results: In all, 158 patients underwent 285 BALs. The overall incidence for VAP was 42%. Patients with episodes of VAP and SIRS were well matched for age, Injury Severity Score, APACHE II score, and Glasgow Coma Scale score. The average CPIS was 6.8 in patients with SIRS and 6.9 for those with VAP. Using a CPIS >6 as the threshold for VAP only yielded a sensitivity of 61% and a specificity of 43%. Conclusions: CPIS cannot differentiate VAP from SIRS in critically injured patients. Using CPIS to initiate antibiotic therapy in trauma patients could be harmful. Whether CPIS is useful to deter(J Trauma 2006;60(3))Back to top
Interstitial Lung Disease
Acute infectious ILD: mycoplasma, chlamydia, legionella, Coxiella , Anthrax, Tularemia, Histoplasmosis, Coccidioidomicosis, PCP, TB, influenza/para influenza, RSV, adenovirus.
Reactive ILD: allergic, BOOP, drug induced, eosinophilic, mold allergic (Stachybotrys, aspergillus…rare…) etc.
I would perform urine test for legionella, complement fixation for coxiella, serologies for influenza, parainfluenza, adenovirus, RSV and HIV, and, if he is hospitalized for his disease would consider 1)BAL, citology, cultures, and direct testing for all of the suspects mentioned before, including molds… 2) starting him on a macrolide and a betalactam or a respiratory fluoroquinolone 3)a trial of corticosteroids if there is strong suspicion of allergic/eosinophillic pneumonitis, esp if the CBC with ESR and C reactive titrated protein are not helpful, and all tests for infectious agents come negative.
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Hospital Acquired Pneumonia
early onset is day 1-4
late onset is ≥ 5 days
Risk Factors for MDR pathogens antibiotics past 90 Days Hospital past 90 Days Current Hospital >5 days Mech Vent >7 days Regular visits to HD or infusion center Nursing Home or Extended-care facility immunosuppressive disease or therapy high resistance in the community or ICU (from ATS)
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Acute Eosinophilic Pneumonia
- Idiopathic acute eosinophilic pneumonia should be consideredin the differential diagnosis of a patient presenting with acuteonset of fever, dyspnea, cough, hypoxemia, and diffuse pulmonaryinfiltrates.
- Because only one third of patients with idiopathicacute eosinophilicpneumonia have peripheral eosinophilia, theabsence of thisfinding may prevent early consideration of acuteeosinophilicpneumonia and suggest the presence of alternativediagnoses.
- Idiopathic acute eosinophilic pneumonia can bediagnosed ina patient with acute onset of febrile respiratory disease (<30 days), bilateral infiltrates on chest radiograph,hypoxemia,and alveolar eosinophilia with BAL differential cellcount >25% eosinophils, after exclusion of other causesof eosinophilicpneumonia.
- Differential diagnoses of alveolareosinophilia with pulmonaryinfiltrates are extensive, and secondary causes should be excludedbefore making the diagnosis of idiopathicacute eosinophilicpneumonia.
- Idiopathic acute eosinophilicpneumonia responds well to systemiccorticosteroids with rapidimprovement of respiratory failureand normalization of chest radiograph.
Go to source: An 18-Year-Old Woman With Fever, Diffuse Pulmonary Opacities, and Rapid Onset of Respiratory Failure — Vahid and Marik 130 (6): 1938 — Chest
Differential Diagnoses for
Parasite-induced pulmonary eosinophilia Fungal-induced pulmonary eosinophilia Drug-induced pulmonary eosinophilia Antibiotics (nitrofurantoin, dapsone, clarithromycin, minocycline, ethambutol, isoniazid) Antineoplastic (methotrexate, bleomycin, fludarabine) Sulfasalazine Amiodarone Captopril Phenytoin Nonsteroidal antiinflammatory drugs Hematopoietic stem cell transplantation Rheumatoid arthritis AIDS Go to source: Chest — Vahid and Marik 130 (6): 1938 Table 1
Emergency Medicine Journal 2007;24:294-296; doi:10.1136/emj.2007.047845 © 2007 Best evidence topic reports (BETs) Auscultating to diagnose pneumonia CLINICAL BOTTOM LINE In the Emergency Department, pneumonia cannot reliably be confirmed or excluded by auscultation, or indeed physical examination, alone.
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2007 IDSA/ATS Guidelines
Severity-of-illness scores,such as the CURB-65 criteria (confusion, uremia, respiratoryrate, low blood pressure,age 65 years or greater),
The most recent modification of the BTS criteria includes 5 easily measurable factors . Multivariate analysis of 1068 patients identified the following factors as indicators of increased mortality: confusion (based on a specific mental test or disorientation to person, place, or time), BUN level >7 mmol/L (20 mg/dL), respiratory rate 30 breaths/min, low blood pressure (systolic, <90 mm Hg; or diastolic, 60 mm Hg), and age 65 years; this gave rise to the acronym CURB-65. In the derivation and validation cohorts, the 30-day mortality among patients with 0, 1, or 2 factors was 0.7%, 2.1%, and 9.2%, respectively. Mortality was higher when 3, 4, or 5 factors were present and was reported as 14.5%, 40%, and 57%, respectively. The authors suggested that patients with a CURB-65 score of 01 be treated as outpatients, that those with a score of 2 be admitted to the wards, and that patients with a score of 3 often required ICU care. A simplified version (CRB-65), which does not require testing for BUN level, may be appropriate for decision making in a primary care practitioner’s office .
For patients withCURB-65 scores 2, more-intensivetreatmentthat is, hospitalization or, where appropriate and available,intensive in-home health careservicesis usually warranted. (Moderaterecommendation; level III evidence.)
ICU admission decision.
7. Directadmission to an ICUis required for patientswith septic shock requiringvasopressors or with acuterespiratory failure requiring intubationand mechanical ventilation. (Strong recommendation; level II evidence.)
8. Directadmission to an ICUor high-level monitoring unitis recommended for patientswith 3 of theminor criteria for severeCAP listed in table 4.(Moderate recommendation; level IIevidence.)
12. Pretreatment blood samplesfor culture and anexpectorated sputum sample for stain and culture (inpatients with a productivecough) should be obtainedfrom hospitalized patients withthe clinical indications listedin table 5 but areoptional for patients withoutthese conditions. (Moderate recommendation;level I evidence.)
13. Pretreatment Gram stain and culture ofexpectorated sputum should be performed only if agood-quality specimen can beobtained and quality performancemeasures for collection, transport,and processing of samplescan be met. (Moderate recommendation; level II evidence.)
For these reasons,blood cultures are optionalfor all hospitalized patientswith CAP but shouldbe performed selectively (table 5).The yield for positiveblood culture results ishalved by prior antibiotic therapy . Therefore, whenperformed, samples for bloodculture should be obtainedbefore antibiotic administration. However,when multiple risk factorsfor bacteremia are present,blood culture results after initiation of antibiotic therapyare still positive inup to 15% ofcases  and are, therefore, still warranted inthese cases, despite the lower yield.
The strongest indicationfor blood cultures is severe CAP. Patients withsevere CAP are morelikely to be infectedwith pathogens other thanS. pneumoniae, including S. aureus, P. aeruginosa, andother gram-negative bacilli [7780,95, 113, 114]. Manyof the factors predictiveof positive blood cultureresults  overlap withrisk factors for severeCAP (table 4). Therefore, bloodcultures are recommended forall patients with severeCAP because of thehigher yield, the greaterpossibility of the presenceof pathogens not coveredby the usual empiricalantibiotic therapy, and theincreased potential to affectantibiotic management.
Other cultures. Patients withpleural effusions >5 cmin height on alateral upright chest radiograph should undergo thoracentesisto yield material forGram stain and culturefor aerobic and anaerobicbacteria. The yield withpleural fluid cultures islow, but the impacton management decisions issubstantial, in terms ofboth antibiotic choice and the need for drainage.
CA-MRSA. Recently,an increasing incidence ofpneumonia due to CA-MRSAhas been observed [199,200]. CA-MRSA appears in2 patterns: the typicalhospital-acquired strain  and,recently, strains that areepidemiologically, genotypically, and phenotypicallydistinct from hospital-acquired strains[201, 202]. Many ofthe former may representHCAP, because these earlierstudies did not differentiatethis group from typicalCAP. The latter areresistant to fewer antimicrobialsthan are hospital-acquired MRSAstrains and often containa novel type IV SCCmec gene. In addition,most contain the genefor Panton-Valentine leukocidin [200,202], a toxin associatedwith clinical features ofnecrotizing pneumonia, shock, andrespiratory failure, as wellas formation of abscessesand empyemas. The largemajority of cases publishedto date have beenskin infections in children.In a large studyof CA-MRSA in 3communities, 2% of CA-MRSAinfections were pneumonia .However, pneumonia in bothadults  and childrenhas been reported, oftenassociated with preceding influenza.This strain should alsobe suspected in patientswho present with cavitaryinfiltrates without risk factorsfor anaerobic aspiration pneumonia (gingivitis and a riskfor loss of consciousness,such as seizures oralcohol abuse, or esophogealmotility disorders). Diagnosis isusually straightforward, with highyields from sputum andblood cultures in this characteristic clinical scenario. CA-MRSACAP remains rare inmost communities but isexpected to be anemerging problem in CAPtreatment.
Empirical Antimicrobial Therapy
Outpatient treatment. The following regimens arerecommended for outpatient treatmenton the basis of the listed clinical risks.
15. Previouslyhealthy and no riskfactors for DRSP infection:
- Amacrolide (azithromycin, clarithromycin, or erythromycin) (strong recommendation; levelI evidence)
- Doxycycline (weak recommendation;level III evidence)
16. Presence of comorbidities, such as chronicheart, lung, liver, or renal disease; diabetes mellitus;alcoholism; malignancies; asplenia; immunosuppressingconditions or use ofimmunosuppressing drugs; use ofantimicrobials within the previous3 months (in whichcase an alternative froma different class shouldbe selected); or otherrisks for DRSP infection:
- A respiratory fluoroquinolone (moxifloxacin,gemifloxacin, or levofloxacin [750mg]) (strong recommendation; levelI evidence)
- A -lactam plusa macrolide (strong recommendation;level I evidence) (High-doseamoxicillin [e.g., 1 g3 times daily] oramoxicillin-clavulanate [2 g 2times daily] is preferred;alternatives include ceftriaxone, cefpodoxime,and cefuroxime [500 mg2 times daily]; doxycycline[level II evidence] isan alternative to the macrolide.)
17. In regions with a high rate (>25%) ofinfection with high-level (MIC,16 g/mL) macrolide-resistant S. pneumoniae,consider the use ofalternative agents listed abovein recommendation 16 forany patient, including thosewithout comorbidities. (Moderate recommendation;level III evidence.)
The mostcommon pathogens identified fromrecent studies of mild(ambulatory) CAP were S. pneumoniae, M. pneumoniae, C. pneumoniae,and H. influenzae [177, 205].Mycoplasma infection was mostcommon among patients <50years of age withoutsignificant comorbid conditions orabnormal vital signs, whereasS. pneumoniae was the mostcommon pathogen among olderpatients and among thosewith significant underlying disease.Hemophilus infection was found in 5%mostly in patientswith comorbidities. The importanceof therapy for Mycoplasmainfection and Chlamydophila infectionin mild CAP hasbeen the subject of debate, because many infectionsare self-limiting [206, 207].Nevertheless, studies from the1960s of children indicatethat treatment of mildM. pneumoniae CAP reduces themorbidity of pneumonia andshortens the duration ofsymptoms . The evidenceto support specific treatmentof these microorganisms inadults is lacking.
Macrolides havelong been commonly prescribedfor treatment of outpatientswith CAP in theUnited States, because oftheir activity against S. pneumoniaeand the atypical pathogens.This class includes the erythromycin-type agents (including dirithromycin),clarithromycin, and the azalideazithromycin. Although the least expensive, erythromycin is notoften used now, becauseof gastrointestinal intolerance andlack of activity againstH. influenzae. Because of H. influenzae,azithromycin is preferred foroutpatients with comorbidities suchas COPD.
Numerous randomized clinicaltrials have documented theefficacy of clarithromycin andazithromycin as monotherapy foroutpatient CAP, although severalstudies have demonstrated thatclinical failure can occurwith a resistant isolate. When such patients werehospitalized and treated witha -lactam and amacrolide, however, all survivedand generally recovered withoutsignificant complications [188, 189].Most of these patientshad risk factors forwhich therapy with amacrolide alone is notrecommended in the presentguidelines. Thus, for patientswith a significant riskof DRSP infection, monotherapywith a macrolide isnot recommended. Doxycycline is included as a cost-effectivealternative on the basisof in vitro dataindicating effectiveness equivalent tothat of erythromycin forpneumococcal isolates.
The use offluoroquinolones to treat ambulatory patients with CAP withoutcomorbid conditions, risk factorsfor DRSP, or recentantimicrobial use is discouraged because of concern thatwidespread use may leadto the development offluoroquinolone resistance . However,the fraction of totalfluoroquinolone use specifically forCAP is extremely smalland unlikely to leadto increased resistance byitself. More concerning isa recent study suggestingthat many outpatients givena fluoroquinolone may nothave even required an antibiotic, that the doseand duration of treatmentwere often incorrect, andthat another agent oftenshould have been usedas first-line therapy. Thisusage pattern may promotethe rapid development ofresistance to fluoroquinolones .
Comorbiditiesor recent antimicrobial therapy increase the likelihood ofinfection with DRSP andenteric gram-negative bacteria. Forsuch patients, recommended empiricaltherapeutic options include (1)a respiratory fluoroquinolone (moxifloxacin,gemifloxacin, or levofloxacin [750mg daily]) or (2)combination therapy with a-lactam effective against S. pneumoniaeplus a macrolide (doxycyclineas an alternative). Onthe basis of present pharmacodynamic principles, high-dose amoxicillin(amoxicillin [1 g 3times daily] or amoxicillin-clavulanate[2 g 2 times daily]) should target >93%of S. pneumoniae and is the preferred -lactam. Ceftriaxoneis an alternative tohigh-dose amoxicillin when parenteraltherapy is feasible. Selectedoral cephalosporins (cefpodoxime andcefuroxime) can be usedas alternatives , butthese are less activein vitro than high-doseamoxicillin or ceftriaxone. Agentsin the same classas the patient hadbeen receiving previously shouldnot be used to treat patients with recentantibiotic exposure.
Telithromycin is thefirst of the ketolide antibiotics, derived from themacrolide family, and is active against S. pneumoniae thatis resistant to otherantimicrobials commonly used forCAP (including penicillin, macrolides,and fluoroquinolones). Several CAPtrials suggest that telithromycinis equivalent to comparators (including amoxicillin, clarithromycin, andtrovafloxacin) . There havealso been recent postmarketingreports of life-threatening hepatotoxicity. At present, thecommittee is awaiting furtherevaluation of the safetyof this drug bythe FDA before makingits final recommendation.
Inpatient, non-ICU treatment. The following regimens are recommended forhospital ward treatment.
18. A respiratory fluoroquinolone (strong recommendation; levelI evidence)
19. A -lactam plusa macrolide (strong recommendation;level I evidence) (Preferred-lactam agents include cefotaxime,ceftriaxone, and ampicillin; ertapenem for selected patients; withdoxycycline [level III evidence]as an alternative tothe macrolide. A respiratory fluoroquinolone should be usedfor penicillin-allergic patients.)
The recommendationsof combination treatment with a -lactam plus amacrolide or monotherapy witha fluoroquinolone were basedon retrospective studies demonstratinga significant reduction inmortality compared with thatassociated with administration ofa cephalosporin alone .Multiple prospective randomized trialshave demonstrated that eitherregimen results in highcure rates. The majordiscriminating factor between the2 regimens is the patient’s prior antibiotic exposure(within the past 3 months).
Preferred -lactams are thoseeffective against S. pneumoniae andother common, nonatypical pathogenswithout being overly broad spectrum. In January 2002,the Clinical Laboratory StandardsInstitute (formerly the NCCLS)increased the MIC breakpointsfor cefotaxime and ceftriaxonefor nonmeningeal S. pneumoniae infections.These new breakpoints acknowledgethat nonmeningeal infections causedby strains formerly consideredto be intermediately susceptible,or even resistant, canbe treated successfully withusual doses of these-lactams [112, 186, 220].
Tworandomized, double-blind studies showed ertapenem to be equivalentto ceftriaxone [221, 222].It also has excellentactivity against anaerobic organisms,DRSP, and most Enterobacteriaceaespecies (including extended-spectrum -lactamaseproducers, but not P. aeruginosa).Ertapenem may be usefulin treating patients withrisks for infection withthese pathogens and forpatients who have recently received antibiotic therapy. However,clinical experience with thisagent is limited. Other”antipneumococcal, antipseudomonal” -lactam agentsare appropriate when resistantpathogens, such as Pseudomonas,are likely to bepresent. Doxycycline can beused as an alternativeto a macrolide onthe basis of scantdata for treatment ofLegionella infections [171, 223,224].
Two randomized, double-blind studiesof adults hospitalized forCAP have demonstrated thatparenteral azithromycin alone wasas effective, with improvedtolerability, as intravenous cefuroxime,with or without intravenous erythromycin [225, 226]. Inanother study, mortality andreadmission rates were similar,but the mean LOSwas shorter among patientsreceiving azithromycin alone thanamong those receiving otherguideline-recommended therapy . Noneof the 10 patientswith erythromycin-resistant S. pneumoniae infectionsdied or was transferredto the ICU, including6 who received azithromycinalone. Another study showedthat those receiving amacrolide alone had thelowest 30-day mortality butwere the least ill. Such patients wereyounger and were morelikely to be inlower-risk groups.
These studies suggestthat therapy with azithromycinalone can be consideredfor carefully selected patientswith CAP with nonseveredisease (patients admitted primarilyfor reasons other thanCAP) and no riskfactors for infection withDRSP or gram-negative pathogens.However, the emergence ofhigh rates of macrolideresistance in many areasof the country suggeststhat this therapy cannotbe routinely recommended. Initialtherapy should be givenintravenously for most admittedpatients, but some withoutrisk factors for severepneumonia could receive oraltherapy, especially with highlybioavailable agents such asfluoroquinolones. When an intravenous-lactam is combined withcoverage for atypical pathogens,oral therapy with amacrolide or doxycycline isappropriate for selected patientswithout severe pneumonia riskfactors .
Inpatient, ICU treatment. The following regimenis the minimal recommendedtreatment for patients admittedto the ICU.
20. A -lactam(cefotaxime, ceftriaxone, or ampicillin-sulbactam)plus either azithromycin (levelII evidence) or a fluoroquinolone (level I evidence)(strong recommendation) (For penicillin-allergicpatients, a respiratory fluoroquinoloneand aztreonam are recommended.)
Asingle randomized controlled trialof treatment for severeCAP is available. Patientswith shock were excluded;however, among the patientswith mechanical ventilation, treatmentwith a fluoroquinolone alone resulted in a trendtoward inferior outcome .Because septic shock andmechanical ventilation are theclearest reasons for ICUadmission, the majority of ICU patients would stillrequire combination therapy. ICU patients are routinely excludedfrom other trials; therefore,recommendations are extrapolated fromnonsevere cases, in conjunctionwith case series andretrospective analyses of cohortswith severe CAP.
For allpatients admitted to theICU, coverage for S. pneumoniaeand Legionella species should be ensured [78, 230]by using a potentantipneumococcal -lactam and eithera macrolide or afluoroquinolone. Therapy with arespiratory fluoroquinolone alone isnot established for severeCAP , and, ifthe patient has concomitantpneumococcal meningitis, the efficacyof fluoroquinolone monotherapy isuncertain. In addition, 2 prospective observational studies [231,232] and 3 retrospective analyses  have foundthat combination therapy forbacteremic pneumococcal pneumonia isassociated with lower mortality than monotherapy. The mechanismof this benefit isunclear but was principallyfound in the patientswith the most severeillness and has notbeen demonstrated in nonbacteremicpneumococcal CAP studies. Therefore, combination empirical therapy isrecommended for at least 48 h or untilresults of diagnostic testsare known.
In critically illpatients with CAP, alarge number of microorganismsother than S. pneumoniae andLegionella species must beconsidered. A review of9 studies that included890 patients with CAPwho were admitted tothe ICU demonstrates thatthe most common pathogensin the ICU populationwere (in descending orderof frequency) S. pneumoniae, Legionella species,H. influenzae, Enterobacteriaceae species, S. aureus,and Pseudomonas species .The atypical pathogens responsiblefor severe CAP mayvary over time butcan account collectively for20% of severe pneumoniaepisodes. The dominant atypicalpathogen in severe CAPis Legionella , butsome diagnostic bias probablyaccounts for this finding.
The recommended standard empiricalregimen should routinely coverthe 3 most commonpathogens that cause severeCAP, all of theatypical pathogens, and mostof the relevant Enterobacteriaceaespecies. Treatment of MRSAor P. aeruginosa infection isthe main reason to modify the standard empiricalregimen. The following are additions or modifications tothe basic empirical regimen recommended above if thesepathogens are suspected.
21. For Pseudomonasinfection, use an antipneumococcal,antipseudomonal -lactam (piperacillin-tazobactam, cefepime,imipenem, or meropenem) pluseither ciprofloxacin or levofloxacin(750-mg dose) or the above -lactamplus an aminoglycoside andazithromycin or the above -lactam plusan aminoglycoside and anantipneumococcal fluoroquinolone. (For penicillin-allergicpatients, substitute aztreonam forthe above -lactam.) (Moderate recommendation;level III evidence.)
Pseudomonal CAPrequires combination treatment to prevent inappropriate initial therapy,just as Pseudomonas nosocomialpneumonia does . Once susceptibilities are known, treatmentcan be adjusted accordingly.Alternative regimens are providedfor patients who mayhave recently received anoral fluoroquinolone, in whomthe aminoglycoside-containing regimen wouldbe preferred. A consistentGram stain of trachealaspirate, sputum, or bloodis the best indicationfor Pseudomonas coverage. Other,easier-to-treat gram-negative microorganisms mayultimately be proven tobe the causative pathogen, but empirical coverage ofPseudomonas species until cultureresults are known isleast likely to beassociated with inappropriate therapy.Other clinical risk factors for infection with Pseudomonasspecies include structural lungdiseases, such as bronchiectasis,or repeated exacerbations ofsevere COPD leading tofrequent steroid and/or antibioticuse, as well asprior antibiotic therapy .These patients do notnecessarily require ICU admissionfor CAP , so Pseudomonas infection remains aconcern for them even if they are onlyhospitalized on a generalward. The major riskfactor for infection withother serious gram-negative pathogens,such as Klebsiella pneumoniae or Acinetobacter species, is chronicalcoholism.
22. For CA-MRSA infection, addvancomycin or linezolid. (Moderaterecommendation; level III evidence.)
Thebest indicator of S. aureusinfection is the presenceof gram-positive cocci inclusters in a trachealaspirate or in anadequate sputum sample. Thesame findings on preliminaryresults of blood culturesare not as reliable,because of the significantrisk of contamination .Clinical risk factors forS. aureus CAP include end-stagerenal disease, injection drugabuse, prior influenza, andprior antibiotic therapy (especiallywith fluoroquinolones ).
For methicillin-sensitiveS. aureus, the empirical combinationtherapy recommended above, whichincludes a -lactam andsometimes a respiratory fluoroquinolone,should be adequate untilsusceptibility results are availableand specific therapy witha penicillinase-resistant semisynthetic penicillinor first-generation cephalosporin canbe initiated. Both alsooffer additional coverage forDRSP. Neither linezolid nor vancomycin  isan optimal drug formethicillin-sensitive S. aureus.
Although methicillin-resistant strainsof S. aureus are stillthe minority, the excessmortality associated with inappropriateantibiotic therapy  wouldsuggest that empirical coverageshould be considered whenCA-MRSA is a concern.The most effective therapyhas yet to bedefined. The majority ofCA-MRSA strains are moresusceptible in vitro tonon-lactam antimicrobials, including trimethoprim-sulfamethoxazole(TMP-SMX) and fluoroquinolones, thanare hospital-acquired strains. Previousexperience with TMP-SMX inother types of severe infections (endocarditis and septicthrombophlebitis) suggests that TMP-SMXis inferior to vancomycin. Further experience andstudy of the adequacyof TMP-SMX for CA-MRSACAP is clearly needed.Vancomycin has never beenspecifically studied for CAP,and linezolid has beenfound to be betterthan ceftriaxone for bacteremicS. pneumoniae in a nonblindedstudy  and superiorto vancomycin in retrospectiveanalysis of studies involvingnosocomial MRSA pneumonia .Newer agents for MRSAhave recently become available,and others are anticipated.Of the presently availableagents, daptomycin should notbe used for CAP,and no data onpneumonia are available fortigecycline.
A concern with CA-MRSAis necrotizing pneumonia associatedwith production of Panton-Valentineleukocidin and other toxins.Vancomycin clearly does notdecrease toxin production, andthe effect of TMP-SMXand fluoroquinolones on toxinproduction is unclear. Additionof clindamycin or useof linezolid, both ofwhich have been shown to affect toxin productionin a laboratory setting, may warrant theirconsideration for treatment ofthese necrotizing pneumonias .Unfortunately, the emergence ofresistance during therapy withclindamycin has been reported(especially in erythromycin-resistant strains),and vancomycin would stillbe needed for bacterial killing.
Pathogens Suspected on the Basis of Epidemiologic Considerations
Clinicians should be awareof epidemiologic conditions and/orrisk factors that maysuggest that alternative or specific additional antibiotics shouldbe considered. These conditionsand specific pathogens, withpreferred treatment, are listedin tables 8 and9.
Time to First Antibiotic Dose
29. Forpatients admitted through theED, the first antibioticdose should be administeredwhile still in theED. (Moderate recommendation; levelIII evidence.)
Time to firstantibiotic dose for CAPhas recently received significantattention from a quality-of-care perspective. This emphasis isbased on 2 retrospective studies of Medicare beneficiariesthat demonstrated statistically significantlylower mortality among patientswho received early antibiotictherapy [109, 264]. Theinitial study suggested abreakpoint of 8 h, whereas the subsequentanalysis found that 4h was associated withlower mortality . Studiesthat document the timeto first antibiotic dosedo not consistently demonstratethis difference, although none had as large apatient population. Most importantly, prospective trials of careby protocol have not demonstrated a survival benefitto increasing the percentageof patients with CAPwho receive antibiotics within the first 48 h[22, 65]. Early antibioticadministration does not appearto shorten the timeto clinical stability, either, although time offirst dose does appearto correlate with LOS[266, 267]. A problemof internal consistency isalso present, because, inboth studies [109, 264],patients who received antibioticsin the first 2h after presentation actuallydid worse than thosewho received antibiotics 24h after presentation. Forthese and other reasons,the committee did notfeel that a specifictime window for deliveryof the first antibioticdose should be recommended. However, the committee doesfeel that therapy shouldbe administered as soonas possible after thediagnosis is considered likely.
Conversely,a delay in antibiotictherapy has adverse consequencesin many infections. Forcritically ill, hemodynamically unstablepatients, early antibiotic therapyshould be encouraged, althoughno prospective data supportthis recommendation. Delay inbeginning antibiotic treatment duringthe transition from theED is not uncommon.Especially with the frequentuse of once-daily antibioticsfor CAP, timing andcommunication issues may result in patients not receivingantibiotics for >8 hafter hospital admission. Thecommittee felt that thebest and most practicalresolution to this issuewas that the initialdose be given inthe ED .
Data fromthe Medicare database indicatedthat antibiotic treatment beforehospital admission was also associated with lower mortality. Given that thereare even more concernsregarding timing of thefirst dose of antibioticwhen the patient is directly admitted to abusy inpatient unit, provisionof the first dosein the physician’s officemay be best ifthe recommended oral orintramuscular antibiotics are availablein the office.
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Healthcare Associated Pneumonia
HAP 48 hrs or more after admission with no preceding infection VAP 48-72 hours or more after intubation. HCAP Infection developing within 90 days of at least a 2-day hospitalization Infection in nursing-home or long-term care residents Infection within 30 days of receiving IV antimicrobial therapy, chemotherapy, hemodialysis, or wound care Infection following a hospital or HD clinic visit Contact with multidrug-resistant pathogens Risk Factors for Multidrug Resistant Pathogens Antimicrobial therapy in the preceding 90 days current hospitilization of 5 days or more High frequency of antimicrobial resistance in the community or specific hospital unit Immunosuppressive disease and/or therapy HCAP Risk Factors Ceftazidime 2 g Q8 and Cipro 400 mg Q8 is good HCAP regimen
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Acute Interstitial Pneumonia
We see this entity probably 2-4 times a year. AIP is really a wastebasket term, in that its not clear that AIP is really a single entity or just an expression of severe lung injury from an insult that is not readily apparent. Some of these patients may really have severe viral pneumonia, some may have an non infectious inflammatory process. For example about 40% of patients with IPF may have sudden accelerated progression. In older patients there is probably a subset with preexisting early IPF with then flame out with an AIP like syndrome. In any case our approach is the same as you describe, The usual ARDS vent support/ lung protection, empiric ATB, steroids starting at fairly high doses ( 2mg/kg of Solumedrol, sometimes we pulse dose with 250 mg qid x 48hrs) Our workup is usually BAL to r/o infection, possibly pANCA, cANCA, antiGBM Ab to r/o vasculitis. ( about the only thing that changes rx would be a dx of vasculitis which might in dicate a need for plasmapharesis or cytoxan.) Almost never bx as the resulting result of “diffuse alveolar damage” tends not to help. I would agree the mortality is high, but we have had survivors. One case was female in late 20s, prone vent, PCIRV, NO and multiple chest tubes, made it out of ICU and actually was in ok shape about a year later ( I followed her as outpatient for a while.) She had mildly restrictive PFT for about a year, but no sx.Michael DePietro MDDirector Medical Intensive Care Unit
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PIRO Score to predict high risk of death
a) Low, 0-2 points; b) Mild, 3 points; c) high, 4 points; and d) Very high, 5-8 points
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Sudden Cardiac Arrest
In patients with preexisting pneumonia, cardiac arrest may occur in the absence of preceding shock or respiratory failure. Physicians should be alert to the possibility of abrupt cardiopulmonary collapse, and future studies should address this possibility. The mechanism may involve myocardial ischemia, a maladaptive response to hypoxia, sepsis-related cardiomyopathy, or other phenomena. (CHEST June 2012 vol. 141 no. 6 1528-1536)Back to top