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)
http://www.jointcommission.org
Consider PE, HIV
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
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
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
Urinary test (Spec 90%, Sens 50-80%)
It's Crap
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.
Must Cover these 6 for all CAP
| Typical | Atypical |
| S. Pneumo | Legionella |
| H. Flu | Chlamydia |
| M. Catarrhalis | Mycoplasma |
COPD, ETOH, Diabetics
IVDA, small infiltrates, necrotizing
ETOH, necrotizing, currant jelly sputum
COPD
can do
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.
| 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)
|
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)
Pseudomonas 52%
S. Aureus 13%
S Marcescens 10%
Klebsiella 6%
E. Coli 1.5%
Hospital Acquired Pneumonia ((Pharm Ther 1999, 24: 390-396)
Pseudomonas 17%
S. Aureus 14.6%
Enterobacter 10.4%
Klebsiella 7.4%
E. Coli 6.4
Unusual Causes:
Tularemia-rabbits
Psittacosis-birds
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
NEJM 2001;344:665
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.
Histoplasmosis
Most common in
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
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
Coccidioidomycosis
Sx same as above
Dx c IgG
Ampho B
Blastomycosis
Mass-like opacities can resemble
Dx by visualization of the yeast in sputum samples
Rx Ampho B
Aspergillosis
Mold
Neutropenia or AIDS
Fever cough and chest pain
Diffuse infiltrates or nodular opacities (peripherally located wedge shaped opacity)
Ampho B
Mucormycosis
Mold from
Immunocompromised only
Surgical Resection of diseased tissue and Ampho B
Cryptococcosis
Yeast
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.
Candida
Yeast
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
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)
Out patient:
zithromax or biaxin (alt. Fluroquinolones)
Inpatient:
Ceftriaxone and Zithromax IV for most patients
Mild pneumonia can get zithro alone
increased risk of gram negative (kleb) such as etoh:
ceft + zithro
Zosyn, cefepime, imipenem, meropenem
plus
cipro or levo (750) or (amino and zithromax)
pcn allergy: aztreonam plus amino plus either macrolide or fluorquinolone
ceft + zith + clinda (alt: levo/clinda or b-lactam/lactamase inhibitor)
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
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)
Also
Confusion
Urea >20
RR >30
BP<90
Age>65
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.
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.
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
Diagnosis
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
|
||||||||||||||||||||||||||||||||||
* 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
|
||||||||||||||||||||||||||||||||||||||
* 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 4–5 µg/ml.
Trough levels for vancomycin should be 15–20 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 patient’s 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 (44–46). 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 trimethoprim–sulfamethoxazole, ticarcillin–clavulanate, 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 8–16 g/ml, and high-level vancomycin-
resistant S. aureus, with an MIC of 32–1,024 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, 66–69).
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, 66–69). 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-care–associated 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 (70–75). 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, 76–78).
Respiratory syncytial virus outbreaks of bronchiolitis and pneumonia
are more common in children’s 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 person–fomite–person transmission (3, 79–81). 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,
81–90). Amantadine and rimantadine are effective only for treatment
and prophylaxis against influenzaAstrains, whereas neuraminidase
inhibitors are effective against both influenza A and B.
• 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 therapy
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))
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.
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)
Clinical Pearls
Differential Diagnoses for
|
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.
Severity-of-illness scores, such as the CURB-65 criteria (confusion, uremia, respiratory rate, low blood pressure, age 65 years or greater),
The most recent modification of the BTS criteria includes 5 easily measurable factors [45]. 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 0–1 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 [54].
For patients with CURB-65 scores
2,
more-intensive treatment—that is, hospitalization or,
where appropriate and available, intensive in-home health care
services—is usually warranted. (Moderate recommendation; level
III evidence.)
ICU admission decision.
7. Direct admission to an ICU is required for patients with septic shock requiring vasopressors or with acute respiratory failure requiring intubation and mechanical ventilation. (Strong recommendation; level II evidence.)
8. Direct admission to an ICU or high-level monitoring unit is recommended for patients with 3 of the minor criteria for severe CAP listed in table 4. (Moderate recommendation; level II evidence.)
12. Pretreatment blood samples for culture and an expectorated sputum sample for stain and culture (in patients with a productive cough) should be obtained from hospitalized patients with the clinical indications listed in table 5 but are optional for patients without these conditions. (Moderate recommendation; level I evidence.)
13. Pretreatment Gram stain and culture of expectorated sputum should be performed only if a good-quality specimen can be obtained and quality performance measures for collection, transport, and processing of samples can be met. (Moderate recommendation; level II evidence.)
For these reasons, blood cultures are optional for all hospitalized patients with CAP but should be performed selectively (table 5). The yield for positive blood culture results is halved by prior antibiotic therapy [95]. Therefore, when performed, samples for blood culture should be obtained before antibiotic administration. However, when multiple risk factors for bacteremia are present, blood culture results after initiation of antibiotic therapy are still positive in up to 15% of cases [95] and are, therefore, still warranted in these cases, despite the lower yield.
The strongest indication for blood cultures is severe CAP. Patients with severe CAP are more likely to be infected with pathogens other than S. pneumoniae, including S. aureus, P. aeruginosa, and other gram-negative bacilli [77–80, 95, 113, 114]. Many of the factors predictive of positive blood culture results [95] overlap with risk factors for severe CAP (table 4). Therefore, blood cultures are recommended for all patients with severe CAP because of the higher yield, the greater possibility of the presence of pathogens not covered by the usual empirical antibiotic therapy, and the increased potential to affect antibiotic management.
Other cultures. Patients with pleural effusions >5 cm in height on a lateral upright chest radiograph [111] should undergo thoracentesis to yield material for Gram stain and culture for aerobic and anaerobic bacteria. The yield with pleural fluid cultures is low, but the impact on management decisions is substantial, in terms of both antibiotic choice and the need for drainage.
CA-MRSA. Recently, an increasing incidence of pneumonia due to CA-MRSA has been observed [199, 200]. CA-MRSA appears in 2 patterns: the typical hospital-acquired strain [80] and, recently, strains that are epidemiologically, genotypically, and phenotypically distinct from hospital-acquired strains [201, 202]. Many of the former may represent HCAP, because these earlier studies did not differentiate this group from typical CAP. The latter are resistant to fewer antimicrobials than are hospital-acquired MRSA strains and often contain a novel type IV SCCmec gene. In addition, most contain the gene for Panton-Valentine leukocidin [200, 202], a toxin associated with clinical features of necrotizing pneumonia, shock, and respiratory failure, as well as formation of abscesses and empyemas. The large majority of cases published to date have been skin infections in children. In a large study of CA-MRSA in 3 communities, 2% of CA-MRSA infections were pneumonia [203]. However, pneumonia in both adults [204] and children has been reported, often associated with preceding influenza. This strain should also be suspected in patients who present with cavitary infiltrates without risk factors for anaerobic aspiration pneumonia (gingivitis and a risk for loss of consciousness, such as seizures or alcohol abuse, or esophogeal motility disorders). Diagnosis is usually straightforward, with high yields from sputum and blood cultures in this characteristic clinical scenario. CA-MRSA CAP remains rare in most communities but is expected to be an emerging problem in CAP treatment.
Empirical Antimicrobial Therapy
Outpatient treatment. The following regimens are recommended for outpatient treatment on the basis of the listed clinical risks.
15. Previously healthy and no risk factors for DRSP infection:
16. Presence of comorbidities, such as chronic heart, lung, liver, or renal disease; diabetes mellitus; alcoholism; malignancies; asplenia; immunosuppressing conditions or use of immunosuppressing drugs; use of antimicrobials within the previous 3 months (in which case an alternative from a different class should be selected); or other risks for DRSP infection:
-lactam
plus a macrolide (strong recommendation; level
I evidence) (High-dose amoxicillin [e.g., 1 g 3 times
daily] or amoxicillin-clavulanate [2 g 2 times daily]
is preferred; alternatives include ceftriaxone, cefpodoxime,
and cefuroxime [500 mg 2 times daily]; doxycycline
[level II evidence] is an alternative to the
macrolide.)
17. In regions with a
high rate (>25%) of infection with high-level (MIC,
16
g/mL)
macrolide-resistant S. pneumoniae, consider the use of
alternative agents listed above in recommendation 16 for
any patient, including those without comorbidities. (Moderate
recommendation; level III evidence.)
The most common pathogens identified from recent studies of mild (ambulatory) CAP were S. pneumoniae, M. pneumoniae, C. pneumoniae, and H. influenzae [177, 205]. Mycoplasma infection was most common among patients <50 years of age without significant comorbid conditions or abnormal vital signs, whereas S. pneumoniae was the most common pathogen among older patients and among those with significant underlying disease. Hemophilus infection was found in 5%—mostly in patients with comorbidities. The importance of therapy for Mycoplasma infection and Chlamydophila infection in mild CAP has been the subject of debate, because many infections are self-limiting [206, 207]. Nevertheless, studies from the 1960s of children indicate that treatment of mild M. pneumoniae CAP reduces the morbidity of pneumonia and shortens the duration of symptoms [208]. The evidence to support specific treatment of these microorganisms in adults is lacking.
Macrolides have long been commonly prescribed for treatment of outpatients with CAP in the United States, because of their activity against S. pneumoniae and the atypical pathogens. This class includes the erythromycin-type agents (including dirithromycin), clarithromycin, and the azalide azithromycin. Although the least expensive, erythromycin is not often used now, because of gastrointestinal intolerance and lack of activity against H. influenzae. Because of H. influenzae, azithromycin is preferred for outpatients with comorbidities such as COPD.
Numerous randomized clinical trials have documented the
efficacy of clarithromycin and azithromycin as monotherapy for
outpatient CAP, although several studies have demonstrated that
clinical failure can occur with a resistant isolate.
When such patients were hospitalized and treated with a
-lactam and a
macrolide, however, all survived and generally recovered
without significant complications [188,
189]. Most of these patients had risk
factors for which therapy with a macrolide alone is not
recommended in the present guidelines. Thus, for patients
with a significant risk of DRSP infection, monotherapy
with a macrolide is not recommended. Doxycycline is
included as a cost-effective alternative on the basis of
in vitro data indicating effectiveness equivalent to that
of erythromycin for pneumococcal isolates.
The use of fluoroquinolones to treat ambulatory patients with CAP without comorbid conditions, risk factors for DRSP, or recent antimicrobial use is discouraged because of concern that widespread use may lead to the development of fluoroquinolone resistance [185]. However, the fraction of total fluoroquinolone use specifically for CAP is extremely small and unlikely to lead to increased resistance by itself. More concerning is a recent study suggesting that many outpatients given a fluoroquinolone may not have even required an antibiotic, that the dose and duration of treatment were often incorrect, and that another agent often should have been used as first-line therapy. This usage pattern may promote the rapid development of resistance to fluoroquinolones [209].
Comorbidities or recent antimicrobial therapy
increase the likelihood of infection with DRSP and enteric
gram-negative bacteria. For such patients, recommended empirical
therapeutic options include (1) a respiratory fluoroquinolone
(moxifloxacin, gemifloxacin, or levofloxacin [750 mg
daily]) or (2) combination therapy with a
-lactam
effective against S. pneumoniae plus a macrolide (doxycycline
as an alternative). On the basis of present
pharmacodynamic principles, high-dose amoxicillin (amoxicillin [1 g 3
times daily] or amoxicillin-clavulanate [2 g 2 times
daily]) should target >93% of S. pneumoniae and is
the preferred -lactam.
Ceftriaxone is an alternative to high-dose amoxicillin
when parenteral therapy is feasible. Selected oral
cephalosporins (cefpodoxime and cefuroxime) can be used as
alternatives [210], but these are
less active in vitro than high-dose amoxicillin or
ceftriaxone. Agents in the same class as the patient had
been receiving previously should not be used to
treat patients with recent antibiotic exposure.
Telithromycin is the first of the ketolide antibiotics, derived from the macrolide family, and is active against S. pneumoniae that is resistant to other antimicrobials commonly used for CAP (including penicillin, macrolides, and fluoroquinolones). Several CAP trials suggest that telithromycin is equivalent to comparators (including amoxicillin, clarithromycin, and trovafloxacin) [211–214]. There have also been recent postmarketing reports of life-threatening hepatotoxicity [215]. At present, the committee is awaiting further evaluation of the safety of this drug by the FDA before making its final recommendation.
Inpatient, non-ICU treatment. The following regimens are recommended for hospital ward treatment.
18. A respiratory fluoroquinolone (strong recommendation; level I evidence)
19. A
-lactam
plus a macrolide (strong recommendation; level I
evidence) (Preferred
-lactam agents
include cefotaxime, ceftriaxone, and ampicillin; ertapenem
for selected patients; with doxycycline [level III evidence]
as an alternative to the macrolide. A respiratory
fluoroquinolone should be used for penicillin-allergic patients.)
The recommendations of combination treatment with
a -lactam plus
a macrolide or monotherapy with a fluoroquinolone were
based on retrospective studies demonstrating a significant
reduction in mortality compared with that associated with
administration of a cephalosporin alone [216–219].
Multiple prospective randomized trials have demonstrated that
either regimen results in high cure rates. The major
discriminating factor between the 2 regimens is the
patient's prior antibiotic exposure (within the past 3
months).
Preferred
-lactams are
those effective against S. pneumoniae and other
common, nonatypical pathogens without being overly broad
spectrum. In January 2002, the Clinical Laboratory Standards
Institute (formerly the NCCLS) increased the MIC breakpoints
for cefotaxime and ceftriaxone for nonmeningeal S.
pneumoniae infections. These new breakpoints acknowledge
that nonmeningeal infections caused by strains formerly
considered to be intermediately susceptible, or even
resistant, can be treated successfully with usual doses of
these
-lactams [112,
186, 220].
Two randomized, double-blind studies showed
ertapenem to be equivalent to ceftriaxone [221,
222]. It also has excellent
activity against anaerobic organisms, DRSP, and most
Enterobacteriaceae species (including extended-spectrum
-lactamase
producers, but not P. aeruginosa). Ertapenem may be
useful in treating patients with risks for infection with
these pathogens and for patients who have recently
received antibiotic therapy. However, clinical experience with this
agent is limited. Other "antipneumococcal, antipseudomonal"
-lactam agents
are appropriate when resistant pathogens, such as
Pseudomonas, are likely to be present. Doxycycline can
be used as an alternative to a macrolide on the
basis of scant data for treatment of Legionella
infections [171, 223,
224].
Two randomized, double-blind studies of adults hospitalized for CAP have demonstrated that parenteral azithromycin alone was as effective, with improved tolerability, as intravenous cefuroxime, with or without intravenous erythromycin [225, 226]. In another study, mortality and readmission rates were similar, but the mean LOS was shorter among patients receiving azithromycin alone than among those receiving other guideline-recommended therapy [227]. None of the 10 patients with erythromycin-resistant S. pneumoniae infections died or was transferred to the ICU, including 6 who received azithromycin alone. Another study showed that those receiving a macrolide alone had the lowest 30-day mortality but were the least ill [219]. Such patients were younger and were more likely to be in lower-risk groups.
These studies suggest that therapy with azithromycin
alone can be considered for carefully selected patients
with CAP with nonsevere disease (patients admitted primarily
for reasons other than CAP) and no risk factors for
infection with DRSP or gram-negative pathogens. However,
the emergence of high rates of macrolide resistance in
many areas of the country suggests that this therapy
cannot be routinely recommended. Initial therapy should be
given intravenously for most admitted patients, but some
without risk factors for severe pneumonia could receive
oral therapy, especially with highly bioavailable agents
such as fluoroquinolones. When an intravenous
-lactam is
combined with coverage for atypical pathogens, oral
therapy with a macrolide or doxycycline is appropriate for
selected patients without severe pneumonia risk factors [228].
Inpatient, ICU treatment. The following regimen is the minimal recommended treatment for patients admitted to the ICU.
20. A
-lactam
(cefotaxime, ceftriaxone, or ampicillin-sulbactam) plus
either azithromycin (level II evidence) or a
fluoroquinolone (level I evidence) (strong recommendation) (For
penicillin-allergic patients, a respiratory fluoroquinolone
and aztreonam are recommended.)
A single randomized controlled trial of treatment for severe CAP is available. Patients with shock were excluded; however, among the patients with mechanical ventilation, treatment with a fluoroquinolone alone resulted in a trend toward inferior outcome [229]. Because septic shock and mechanical ventilation are the clearest reasons for ICU admission, the majority of ICU patients would still require combination therapy. ICU patients are routinely excluded from other trials; therefore, recommendations are extrapolated from nonsevere cases, in conjunction with case series and retrospective analyses of cohorts with severe CAP.
For all patients admitted to the ICU, coverage for
S. pneumoniae and Legionella species should
be ensured [78, 230]
by using a potent antipneumococcal
-lactam and
either a macrolide or a fluoroquinolone. Therapy with a
respiratory fluoroquinolone alone is not established for severe
CAP [229], and, if the patient has
concomitant pneumococcal meningitis, the efficacy of
fluoroquinolone monotherapy is uncertain. In addition, 2
prospective observational studies [231,
232] and 3 retrospective
analyses [233–235]
have found that combination therapy for bacteremic
pneumococcal pneumonia is associated with lower mortality
than monotherapy. The mechanism of this benefit is unclear
but was principally found in the patients with the most
severe illness and has not been demonstrated in
nonbacteremic pneumococcal CAP studies. Therefore,
combination empirical therapy is recommended for at least
48 h or until results of diagnostic tests are known.
In critically ill patients with CAP, a large
number of microorganisms other than S. pneumoniae and
Legionella species must be considered. A review of
9 studies that included 890 patients with CAP who
were admitted to the ICU demonstrates that the most common
pathogens in the ICU population were (in descending order
of frequency) S. pneumoniae, Legionella species, H.
influenzae, Enterobacteriaceae species, S. aureus, and
Pseudomonas species [171]. The atypical
pathogens responsible for severe CAP may vary over time
but can account collectively for
20% of
severe pneumonia episodes. The dominant atypical pathogen
in severe CAP is Legionella [230], but
some diagnostic bias probably accounts for this finding
[78].
The recommended standard empirical regimen should routinely cover the 3 most common pathogens that cause severe CAP, all of the atypical pathogens, and most of the relevant Enterobacteriaceae species. Treatment of MRSA or P. aeruginosa infection is the main reason to modify the standard empirical regimen. The following are additions or modifications to the basic empirical regimen recommended above if these pathogens are suspected.
21. For Pseudomonas
infection, use an antipneumococcal, antipseudomonal
-lactam
(piperacillin-tazobactam, cefepime, imipenem, or meropenem) plus
either ciprofloxacin or levofloxacin (750-mg dose)
or
the above -lactam
plus an aminoglycoside and azithromycin
or
the above -lactam
plus an aminoglycoside and an antipneumococcal
fluoroquinolone. (For penicillin-allergic patients, substitute
aztreonam for the above
-lactam.)
(Moderate recommendation; level III evidence.)
Pseudomonal CAP requires combination treatment to prevent inappropriate initial therapy, just as Pseudomonas nosocomial pneumonia does [131]. Once susceptibilities are known, treatment can be adjusted accordingly. Alternative regimens are provided for patients who may have recently received an oral fluoroquinolone, in whom the aminoglycoside-containing regimen would be preferred. A consistent Gram stain of tracheal aspirate, sputum, or blood is the best indication for Pseudomonas coverage. Other, easier-to-treat gram-negative microorganisms may ultimately be proven to be the causative pathogen, but empirical coverage of Pseudomonas species until culture results are known is least likely to be associated with inappropriate therapy. Other clinical risk factors for infection with Pseudomonas species include structural lung diseases, such as bronchiectasis, or repeated exacerbations of severe COPD leading to frequent steroid and/or antibiotic use, as well as prior antibiotic therapy [131]. These patients do not necessarily require ICU admission for CAP [236], so Pseudomonas infection remains a concern for them even if they are only hospitalized on a general ward. The major risk factor for infection with other serious gram-negative pathogens, such as Klebsiella pneumoniae or Acinetobacter species, is chronic alcoholism.
22. For CA-MRSA infection, add vancomycin or linezolid. (Moderate recommendation; level III evidence.)
The best indicator of S. aureus infection is the presence of gram-positive cocci in clusters in a tracheal aspirate or in an adequate sputum sample. The same findings on preliminary results of blood cultures are not as reliable, because of the significant risk of contamination [95]. Clinical risk factors for S. aureus CAP include end-stage renal disease, injection drug abuse, prior influenza, and prior antibiotic therapy (especially with fluoroquinolones [237]).
For methicillin-sensitive S. aureus, the empirical
combination therapy recommended above, which includes a
-lactam and
sometimes a respiratory fluoroquinolone, should be adequate
until susceptibility results are available and specific
therapy with a penicillinase-resistant semisynthetic penicillin
or first-generation cephalosporin can be initiated. Both also
offer additional coverage for DRSP. Neither linezolid [241]
nor vancomycin [238] is an
optimal drug for methicillin-sensitive S. aureus.
Although methicillin-resistant strains of S. aureus
are still the minority, the excess mortality associated
with inappropriate antibiotic therapy [80] would
suggest that empirical coverage should be considered when
CA-MRSA is a concern. The most effective therapy has
yet to be defined. The majority of CA-MRSA strains are
more susceptible in vitro to non–-lactam
antimicrobials, including trimethoprim-sulfamethoxazole (TMP-SMX) and
fluoroquinolones, than are hospital-acquired strains. Previous
experience with TMP-SMX in other types of severe
infections (endocarditis and septic thrombophlebitis) suggests that
TMP-SMX is inferior to vancomycin [239].
Further experience and study of the adequacy of TMP-SMX
for CA-MRSA CAP is clearly needed. Vancomycin has never
been specifically studied for CAP, and linezolid has been
found to be better than ceftriaxone for bacteremic
S. pneumoniae in a nonblinded study [240]
and superior to vancomycin in retrospective analysis of
studies involving nosocomial MRSA pneumonia [241].
Newer agents for MRSA have recently become available,
and others are anticipated. Of the presently available
agents, daptomycin should not be used for CAP, and
no data on pneumonia are available for tigecycline.
A concern with CA-MRSA is necrotizing pneumonia associated with production of Panton-Valentine leukocidin and other toxins. Vancomycin clearly does not decrease toxin production, and the effect of TMP-SMX and fluoroquinolones on toxin production is unclear. Addition of clindamycin or use of linezolid, both of which have been shown to affect toxin production in a laboratory setting [242], may warrant their consideration for treatment of these necrotizing pneumonias [204]. Unfortunately, the emergence of resistance during therapy with clindamycin has been reported (especially in erythromycin-resistant strains), and vancomycin would still be needed for bacterial killing.
Pathogens Suspected on the Basis of Epidemiologic Considerations
Clinicians should be aware of epidemiologic conditions and/or risk factors that may suggest that alternative or specific additional antibiotics should be considered. These conditions and specific pathogens, with preferred treatment, are listed in tables 8 and 9.
Time to First Antibiotic Dose
29. For patients admitted through the ED, the first antibiotic dose should be administered while still in the ED. (Moderate recommendation; level III evidence.)
Time to first antibiotic dose for CAP has recently received significant attention from a quality-of-care perspective. This emphasis is based on 2 retrospective studies of Medicare beneficiaries that demonstrated statistically significantly lower mortality among patients who received early antibiotic therapy [109, 264]. The initial study suggested a breakpoint of 8 h [264], whereas the subsequent analysis found that 4 h was associated with lower mortality [109]. Studies that document the time to first antibiotic dose do not consistently demonstrate this difference, although none had as large a patient population. Most importantly, prospective trials of care by protocol have not demonstrated a survival benefit to increasing the percentage of patients with CAP who receive antibiotics within the first 4–8 h [22, 65]. Early antibiotic administration does not appear to shorten the time to clinical stability, either [265], although time of first dose does appear to correlate with LOS [266, 267]. A problem of internal consistency is also present, because, in both studies [109, 264], patients who received antibiotics in the first 2 h after presentation actually did worse than those who received antibiotics 2–4 h after presentation. For these and other reasons, the committee did not feel that a specific time window for delivery of the first antibiotic dose should be recommended. However, the committee does feel that therapy should be administered as soon as possible after the diagnosis is considered likely.
Conversely, a delay in antibiotic therapy has adverse consequences in many infections. For critically ill, hemodynamically unstable patients, early antibiotic therapy should be encouraged, although no prospective data support this recommendation. Delay in beginning antibiotic treatment during the transition from the ED is not uncommon. Especially with the frequent use of once-daily antibiotics for CAP, timing and communication issues may result in patients not receiving antibiotics for >8 h after hospital admission. The committee felt that the best and most practical resolution to this issue was that the initial dose be given in the ED [22].
Data from the Medicare database indicated that antibiotic treatment before hospital admission was also associated with lower mortality [109]. Given that there are even more concerns regarding timing of the first dose of antibiotic when the patient is directly admitted to a busy inpatient unit, provision of the first dose in the physician's office may be best if the recommended oral or intramuscular antibiotics are available in the office.
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
