Diagnosis
Infection of the lung (NEJM Review 2015).
Besides blood and sputum cultures, there are a variety of diagnostic tests depending on which pathogen is a concern. Gram stains have always been questionable for making a diagnosis, but I can't give them up. For CAP:
"Gram stain of sputum samples was useful in guiding microbiological diagnosis of CAP in 23% of patients. The Gram stain and culture of sputum samples obtained from patients who have received antibiotic treatment was unreliable. The presence of gram-positive diplococci and gram-negative coccobacilli was highly specific for the culture of S. pneumoniae and H. influenzae, respectively (PubMed)."
vs
"In a meta-analysis examining respiratory specimen Gram stain for diagnosis of ventilator-associated pneumonia, absence of bacteria on Gram stain had a high negative predictive value, but a positive Gram stain correlated poorly with organisms recovered in culture (PubMed)."
The guidelines: Sputum culture: patients with severe disease as well as in all inpatients empirically treated for MRSA or P. aeruginosa. Blood culture recommended in patients with severe disease as well as in all inpatients empirically treated for MRSA or P. aeruginosa.
My take? A good sputum gram stain is one of many pieces of information needed to determine what the cause of the pneumonia is/might be.
I tend not to think in terms of VAP, HAP, CAP which are CRAP (except you should follow the treatment guidelines). I think of pneumonias as differentiated by risks, CXR pattern, gram stain, and culture.
A sputum culture is no worse than a BAL for a microbiologic diagnosis (PubMed).
30% of patients with clinical CAP and a negative CXR will have a positive CT (PubMed). Are we going to CT everyone? Nope.
But a bedside ultrasound may be the way to go (PubMed). If I were younger I would learn the technique.
Legionella and Pneumococcal urine antigens are often routinely ordered, but guidelines suggest only if a severe disease or risk.
"A total of 474 episodes of CAP were included. Streptococcus pneumoniae was the causative pathogen in 171 cases (36.1%). It was detected exclusively by urinary antigen test in 75 cases (43.8%). Sixty-nine patients had CAP caused by a pathogen other than S pneumoniae. Specificity was 96%, positive predictive value ranged from 88.8% to 96.5%, and the positive likelihood ratio ranged from 14.6 to 19.9 (PubMed)."
So not a bad test. And it may allow you to narrow antibiotics. HAHAHAHAHAHAHAHAHA. Like anyone does that when the cultures come back. I kill me.
The Pneumococcal antigen can be positive for a prolonged time after disease: "18 (52.9%) of the 34 patients in the first month after pneumonia diagnosis. In 12 of these positive cases, the test was still positive in the second month, in six patients after 4 months, and in two cases 6 months after the diagnosis of pneumonia (PubMed)."
While the guidelines suggest Legionella and Pneumococcal antigen on everyone, they have low yield: "Recommended indications for SP and LP urinary antigen testing in the IDSA/ATS CAP guidelines have poor sensitivity and specificity for identifying patients with positive tests...No clinical characteristics were strongly associated with positive SP UATs, while features associated with positive LP UATs were hyponatremia, fever, diarrhea, and recent travel." (Pubmed).
And then there are these respiratory panels; mostly used in the ICU.
Admit? Use the CURB 65 Score
- One point each:
- Confusion of new onset (defined as an AMTS of 8 or less)
- Blood Urea nitrogen greater than 7 mmol/l (19 mg/dL)
- Respiratory rate of 30 breaths per minute or greater
- Blood pressure less than 90 mmHg systolic or diastolic blood pressure 60 mmHg or less
- Age 65 or older
- 0—0.6%
- 1—2.7%
- 2—6.8%
- 3—14.0%
- 4—27.8%
- 5—27.8%
- 0-1: Treat as an outpatient
- 2: Consider a short stay in hospital or watch very closely as an outpatient
- 3-5: Requires hospitalization
Epidemiologic Risks
So many variations, depending on the organism, the host and the exposures.
PPI's are a risk in the first month after starting them, he says with a tortured sentence structure (PubMed).
In the elderly, the use of antipsychotics increases the risk of CAP in a dose-dependent manner (PubMed). I am glad MY voices tell me good things.
Post-obstructive pneumonia may be more common; it tends to be slow in onset and have a cavity (Pubmed).
Legionella and Mycoplasma pneumoniae (PubMed) go up when it is humid and in the week following thunderstorms. Multiple studies have demonstrated that Legionella rates go up after rains (PubMed).
Drowning. 90% aspirate and when cultured grow Aeromonas species > Staphylococcus aureus > Pseudomonas species = Haemophilus influenzae > Streptococcus pneumoniae, Klebsiella pneumoniae, Enterobacter cloacae, Acinetobacter species, and Stenotrophomonas maltophilia (PubMed).
And environmental disasters spew soil pathogens into the air for people to inhale. For example, after tornadoes, Alcaligenes xylosoxidans, Burkholderia species, Aspergillus, Pseudomonas putida, and Enterobacter aerogenes are found in patients with pneumonia (PubMed).
Curiously, obesity is protective for survival (PubMed).
Prescription opiates increase risk (PubMed).
Over 40% of patients with CAP will have undiagnosed diabetes or pre-diabetes (PubMed).
When you give the patient with CHF antibiotics for their CHF, you are doing harm: ADHF patients who received IVAB without evidence of infection had longer lengths of stay, required more diuretics, and were more likely to be readmitted compared with ADHF patients not exposed to IVAB(Pubmed)."
Microbiology
The lung does have a low-density microbiome (Pubmed) that can be altered in disease. If stool transplant is barf-o-genic, wait until they try sputum transplants.
50% of the time we get no diagnosis and the cause has changed over the decades. For example, pneumococcus has become uncommon for a variety of reasons, going from 90% of cases to 10% (PubMed). As the French say, the more things change, the more things change.
Common causes (I bet as PCR is more widely used this list will change (PubMed)(Pubmed) include:
- Viral (PubMed): Influenza, RSV, Adenovirus, picornaviruses, and coronaviruses. Rhinovirus is the most common isolated in a 2015 NEJM review.
Mimivirus, a virus so damn big [3rd biggest ever] it can be seen as gram-positive cocci. Really (PubMed) (PubMed).
25% of patients will have a mixed viral/bacterial cause and may have an increased death rate (PubMed). And about 40% of those being admitted with a viral cause will get a bacterial super-infection, usually, but not always, with S. pneumonia (PubMed).
In one adult cohort, the viral cause of pneumonia as Respiratory Syncytial virus 6.1%, Human metapneumovirus 4.5% patients, and influenza in 6.5% of patients (PubMed).
There are always new pathogens cropping up, be it SARS in Asia or coronavirus a Saudi Arabia (PubMed). One day a new pathogen will arise and sweep the world killing us all.
"Clinical manifestations of human metapneumovirus pneumonia include high fever, wheezing in 43%, and respiratory failure in 31% of patients. An elevated number of white blood cells as well as increased levels of C-reactive protein, creatine phosphokinase, and both aspartate and alanine transaminases (PubMed)."
- Bacterial: S. pneumonia (still number one. At least 13.5% of patients with invasive disease will have some sort of hypogammaglobulinemia (PubMed)), Actinomycosis, C. pneumonia, C. psittaci, Coxiella burnetti, K. pneumonia, Legionella spp (probably under-diagnosed; PCR if used routinely can markedly increase the diagnosis, in one study it was from 1 in 9 to 1 in 20 cases of pneumonia (PubMed)), Mycobacterium spp, Mycoplasma pneumoniae, Nocardia spp, P. aeruginosa, S. aureus (for CAP, MRSA accounts for only 2.5% of causative organisms (PubMed)).
When the CXR shows patchy infiltrates, dry cough, and the sputum has WBC but no organisms seen, think atypical and when you think atypical, think Legionella.
Going to use a procalcitonin? Think again "sensitivity and specificity of serum procalcitonin were 0.55 (95% confidence interval [CI], .37-.71; I2 = 95.5%) and 0.76 (95% CI, .62-.86; I2 = 94.1%), respectively. Thus, a procalcitonin level is unlikely to provide reliable evidence either to mandate administration of antibiotics or to enable withholding such treatment in patients with CAP (Pubmed). More like amateur-calcitonin, am I right?
Think Legionella if low sodium (under 133) low platelets (under 177K) and elevated LDH (over 225) (Pubmed).
- most of the time ESBL E. coli and K. pneumonia in ventilated patients are colonization but when found in infection-related ventilator-associated events it doesn't stop the use of unneeded carbapenems (PubMed). But. "E. coli pneumonia isolates from critically ill patients indicate that they belong to the extraintestinal pathogenic E. coli pathovar but have distinguishable lung-specific traits (PubMed)."
Acinetobacter, usually a hospital-acquired pathogen, can cause community-acquired pneumonia, associated with poor hosts (they serve Bud light) and warm, wet environments (PubMed)
When should you worry about MRSA as a cause of CAP? Probably never. S. aureus causes less than 2% of community-acquired pneumonia (except as a complication of influenza), yet 30% of patients get put on anti-Staphylococcal antibiotics. Go figure.
"MRSA pneumonia was observed more frequently in patients with a previous history of MRSA infection (OR = 6.05; P < 0.001), a PSI score ≥120 (OR = 2.40; P = 0.015), intravenous antibiotic treatment within 30 days of pneumonia (OR = 2.23; P = 0.018) (PubMed)."
A negative nares for MRSA had a high specificity and negative predictive value (almost 100%) for ruling out MRSA pneumonia, particularly for CAP/HCAP (PubMed). So MRSA nasal negative? Don't give vancomycin. If the cultures and nasal swab are negative for MRSA it is reasonable to stop antibiotics (PubMed). This is especially true for HAP/ VAP (PubMed).
Intubation, tracheotomy, and 2 bronchoscopies increase the risk of pneumococcal pneumonia (PubMed).
Around 14% will be co-infected with bacteria and a virus; they do poorly (PubMed).
- Parasite: usually as part of a Loeffler's syndrome as worms pass through the lung often with eosinophilia. Roundworms Ascaris lumbricoides, Strongyloides stercoralis, and hookworms Ancylostoma duodenale and Necator americanus, Trichinella spiralis and Schistosomiasis.
- Fungal: Aspergillus, Coccidiomycosis, Cryptococcus, Histoplasma, PJP.
Candida almost NEVER causes pneumonia and can almost always be ignored, even in a BAL. "We concede, by the present data, that it is convincingly proven that Candida species are at most a very rare cause of pneumonia (PubMed)".; 0.07% of positive BAL's will actually be the real deal.
Like most fungal infections, the diagnosis is slow to be made as people do not consider it, even in endemic areas (Pubmed). Take a damn exposure history and know what is in your community.
- Community-Acquired Lobar ('typical') Pneumonia: S. pneumonia (still number one, patients with this disease have a marked increased risk for acute MI, CHF, and arrhythmia (PubMed)), K. pneumonia (especially ETOH abusers), Legionella spp., S. aureus (after influenza or other viral URI; always suspect R sided endocarditis when there is S. aureus in the sputum).
In one study (PubMed) they found an etiology in 90% of patients, with S. pneumonia in combination with a virus about 25% of the time.
- Post Influenza: S. pneumonia, Haemophilus influenza, and S. aureus. (In 2007 MRSA was the most common post influenza pneumonia (PubMed).
- Community-Acquired Interstitial ('atypical') Pneumonia: C. pneumonia, C. psittaci, Coccidioides immitis (29% of people presenting with pneumonia in Arizona had cocci) Coxiella burnetti, Mycoplasma pneumoniae, Legionella spp (is increased shortly after hot, humid, thundershower weather (PubMed)), Influenza, PJP.
- Aspiration Pneumonia: if rasty dentition (i.e. no WAY would you kiss that person) and chronic loss of consciousness from drugs, ETOH, seizures or trauma) then anaerobes and Streptococci. They usually present as lung abscess and empyema. People with good dentition (i.e. kissable) do not have a big load of anaerobes in their mouth. If the patient has no teeth, they have no anaerobes. Repeat that last sentence until you understand it. Most other aspirations are chemical and do not require antibiotics, but try to stop anyone from giving them. Can't do it. Seriously. An aspiration event is not not not not an aspiration pneumonia and whether community, hospital or ventilator no study or guideline that I can find nothing suggesting that anaerobes are important in acute aspiration events; anaerobes are never isolated. Treating anaerobes because of an acute aspiration event is so stupid it makes my teeth hurt. See the Rant section of Lung Abscess for more. The 2019 NEJM review on aspiration is horrible and I think totally doesn't get it. Ignore it.
And that ain't my opinion, it's backed by SCIENCE: "Prophylactic antimicrobial therapy for patients with acute aspiration pneumonitis does not offer clinical benefit and may generate antibiotic selective pressures that results in the need for escalation of antibiotic therapy among those who develop aspiration pneumonia (PubMed)."
As per the guidelines: "We suggest not routinely adding anaerobic coverage for suspected aspiration pneumonia unless lung abscess or empyema is suspected". Which is kind of stupid with the suspected. What, you don't have a CXR to help you?
- Cavitary Pneumonia: mixed anaerobes PLUS Streptococci (lung abscess), S. aureus, Mycobacterium (Tb and atypical), Actinomycosis, Nocardia, Aspergillus, Mucormycosis, Coccidiomycosis, Cryptococcus, Histoplasma, PJP (on inhaled pentamidine).
- Miliary. Usually, think TB, remember that miliary disease is often due to hematogenous spread of organisms that lodge in the interstitium of the lung and multiply. Many pathogens can cause a miliary pattern (PubMed), and since the disease is not in the alveoli, sputum and bronchoscopy will not get the diagnosis. You need a biopsy.
- Hospital-Acquired or Ventilator Acquired Pneumonia: mostly gram-negative rods of the Pseudomonas variety or S. aureus (especially if a tracheostomy). Occasionally Legionella spp. NOT anaerobes. Ever. So quit using metronidazole. About a third are due to viruses, mostly rhino and metapneumo.
- Immunoincompetent: Cytomegalovirus, PJP, Nocardia, Mycobacterium (Tb and atypical), Aspergillus, Mucormycosis.
Empiric Therapy
From the IDSA Guidelines 2019. Follow the guidelines. When compared to patients who do not receive antibiotics as recommended by the guidelines, those who get therapy by the IDSA have decreased 48 hours (PubMed) and long term mortality (PubMed).
Home or admit? To decide, use the pneumonia severity index. You really should use the calculator, it will improve care and survival (PubMed). Here is an online severity index calculator. And here is the local version.
Do not forget the vaccines; everyone does but it works. By the way, if the patient is getting better, they only need one CXR (PubMed).
As you read the recommendations remember in systemic reviews, for all CAP inpatient/outpatient disease, given as monotherapy or in combination with a beta-lactam, a quinolone leads to more clinical cure than macrolide for all kinds of pneumonia (PubMed).
BUT. Azithromycin and other macrolides with a beta-lactam demonstrated decreased mortality when the cause is Pneumococcus, and Pneumococcus is the most common cause of CAP.
BUT, for all patients, monotherapy with a beta-lactam is non-inferior and maybe better (PubMed)
Specific examples follow. From the IDSA guidelines:
Outpatient treatment
Treatment of CAP in healthy outpatients:
Amoxicillin 1 g, 3 times daily
Doxycycline 100 mg
A macrolide twice daily, but only if local pneumococcal resistance to macrolides is estimated to be <25%. The overall prevalence of pneumococcal macrolide resistance in the United States is estimated to be >30%.
Among patients with significant comorbid chronic illness:
Amoxicillin/clavulanate or a cephalosporin plus a macrolide or doxycycline.
A respiratory fluoroquinolone
But doxycycline use is associated with decreased mortality if they have pneumococcus (PubMed). Except if you are really worried about Mycoplasma pneumoniae: Resistance to macrolides can be as high at 69% (but may make no difference in outcome) in some series and is associated with a prolonged fever if you use a macrolide. Go figure. Treat a patient with an antibiotic that does not work and the patient doesn't do as well.Presence of co-morbidities such as chronic heart, lung, liver or renal disease; diabetes mellitus; alcoholism; malignancies; asplenia; immunosuppressing conditions or use of immunosuppressing drugs; or use of antimicrobials within the previous 3 months (in which case an alternative from a different class should be selected).
A beta-lactam plus a macrolide.
This is the best option. In meta-analysis, "macrolide-based regimens were associated with a significant 22% reduction in mortality compared with non macrolides; however, this benefit did not extend to patients studied in RCTs or patients that received guideline-concordant antibiotics. Our findings suggest guideline concordance is more important than choice of antibiotic when treating CAP (PubMed)." Of course, there is Newton's second law of medical literature. For every study there is an equal and opposite study: "Among patients with clinically suspected CAP admitted to non-ICU wards, a strategy of preferred empirical treatment with beta-lactam monotherapy was non-inferior to strategies with a beta-lactam–macrolide combination or fluoroquinolone monotherapy with regard to 90-day mortality (PubMed) (PubMed)."
But: Clarithromycin for acute exacerbations of chronic obstructive pulmonary disease or community-acquired pneumonia may be associated with increased cardiovascular events (PubMed).
Damned if you do, damned if you do.
OR
A respiratory quinolone.
And you can give the quinolone po with no change in outcome (Pubmed).
And if there is invasive Pneumococcal disease, the use of levofloxacin when resistant has increased mortality (PubMed).
3. In regions with a high rate of infection with high-level (mic > 16 mg/mL) macrolide-resistant Streptococcus pneumoniae, consider the use of alternative agents listed above in (2) for patients without co-morbidities.
Inpatients, non-ICU treatment
As of 2019, the Concept of healthcare-associated pneumonia was abandoned in place of "Emphasis on local epidemiology and validated risk factors to determine need for MRSA or P. aeruginosa coverage. Increased emphasis on deescalation of treatment if cultures are negative." About time. It was a stupid concept and led to the overuse of antibiotics.
A beta-lactam plus a macrolide. I think this is definitely the best option and the data all point to a decrease in mortality with the combination, especially if bacteremia, and who can predict upfront (PubMed) (Pubmed)(PubMed). Doxycycline may be equal to the quinolone (PubMed), but not in the guidelines.
There is a suggestion, not statistically significant (which like as not means it is not real as p was 0.06 and a real significant result should be 0.005, not 0.05 (5 out of 4 Americans Do Not Understand Statistics)), that giving the macrolide first decreases mortality (PubMed). I really doubt it but the literature is what it is.
Or go with
A respiratory quinolone.
Of interest, using a quinolone may be more likely to select for subsequent resistant organisms (PubMed). I increasingly think of quinolones as evil, since most evil is done by those that think they are doing good.
Inpatients, ICU treatment
A beta-lactam (cefotaxime, ceftriaxone, or ampicillin-sulbactam) plus either azithromycin or a respiratory quinolone (for penicillin-allergic patients, a respiratory fluoroquinolone and aztreonam are recommended)
Special concerns
If Pseudomonas is a consideration
An anti-pneumococcal, antipseudomonal beta-lactam (cefepime, imipenem, meropenem, piperacillin-tazobactam,aztreonam)
Remember: Double coverage is associated with increased mortality in a study when treating suspected Pseudomonas and CAP (PubMed).
If MRSA is a consideration, add vancomycin or linezolid.
"...in patients with CAP provide strong evidence that deescalation of antibiotic therapy at 48 hours in accord with microbiological results that do not yield MRSA or P. aeruginosa is safe and reduces duration of antibiotic treatment, length of hospitalization, and complications of broad-spectrum therapy. "
OUTPATIENT
No co-morbidities No recent antibiotics: A macrolide OR doxycycline. Recent antibiotics: moxifloxacin, levofloxacin, or gemifloxacin alone, erythromycin, azithromycin, or clarithromycin PLUS high-dose amoxicillin. OR erythromycin, azithromycin, or clarithromycin PLUS high-dose amoxicillin./clavulanate.
Co-morbidities (COPD, Diabetes, Renal or Congestive Heart Failure, or Malignancy) No recent antibiotics: erythromycin, azithromycin, clarithromycin OR moxifloxacin, levofloxacin, or gemifloxacin.
Recent antibiotics: moxifloxacin, levofloxacin, gemifloxacin alone OR erythromycin, azithromycin, clarithromycin PLUS a beta-lactam Suspected aspiration with infection: amoxicillin-clavulanate OR clarithromycin (I prefer amoxicillin. OR a third-generation cephalosporin PLUS metronidazole).
Post Influenza with bacterial superinfection: (third-generation cephalosporins OR penicillin/beta-lactamase inhibitors PLUS vancomycin) OR moxifloxacin, levofloxacin, or gemifloxacin.
How long to treat? Shorter is better than longer, recent studies with a long-acting azithromycin (PubMed) suggest a single dose will do. Usually, it is 5,7,10 or 14, based on the number of fingers we have or the number of days in the week. I think if we had 8 fingers and 12 day weeks, then patients would be getting some multiple of 8 and 12 days of therapy (PubMed). For uncomplicated CAP, 5 days suffice, and maybe even 3 days total (PubMed).
And, as should come to no surprise to anyone, patients are more adherent with their compliance (or is it compliant with their adherence?) if given a once a day antibiotic (PubMed).
Depending on the population, up to 66% of Mycoplasma pneumoniae, can be macrolide-resistant.
CAP INPATIENT
No recent antibiotics: moxifloxacin, levofloxacin, or gemifloxacin alone OR erythromycin, azithromycin, clarithromycin PLUS cefotaxime or ceftriaxone.
I REALLY prefer the macrolide/beta-lactam combination, as do the guidleines. It probably decreases mortality (PubMed). A meta-analysis (and I never meta-analysis I likeded)(PubMed) suggests it is a waste of time to cover atypicals, but several studies have demonstrated combination therapy with a macrolide (PubMed) increases survival of patients with pneumococcal bacteremia. What kills people is the pneumococcus, not the 'atypicals'. Usually. Some epidemiologic studies suggest that CAP mortality doubles if treatment for atypical pathogens is not given (PubMed).
Recent antibiotics: erythromycin, azithromycin, clarithromycin PLUS cefotaxime or ceftriaxone or moxifloxacin, levofloxacin, alone (regimen selected will depend on the nature of recent antibiotics).
Suspected aspiration with infection: amoxicillin-clavulanate OR clarithromycin or penicillin/beta-lactamase inhibitors or (I prefer amoxicillin OR third-generation cephalosporins PLUS metronidazole).
MRSA pneumonia: with vancomycin push the trough to 15 mcg/ml. Whether this is of benefit is questionable (PubMed) and whether one should add rifampin or change to another agent is unknown.
Is linezolid superior to vancomycin? Data keeps going back and forth with a 2010 meta-analysis suggesting they are equally a piece of crap (PubMed). As of 2012, the preponderance of data and the best clinical trial (PubMed) point to the slight superiority of linezolid for MRSA pneumonia with 10% higher cure rate but a similar 60 day mortality. But then a 2014 review suggests they are equal (PubMed). Sigh. The trend suggests linezolid for pneumonia (PubMed) and the better outcomes may be due to suppression of toxins, at least in the mouse model (PubMed). Although not supported by data, I tend towards linezolid when the mic to vancomycin is >= 1.0, but I am hesitant for bacteremic MRSA infections off all sorts. For patients that are STS, I have been giving ceftaroline and either clindamycin or linezolid based on a hope and a prayer, which is something for an atheist.
How long to treat CAP? Shorter is better than longer, recent studies with a long-acting azithromycin suggest a single dose will do. Usually, it is 5,7,10 or 14, mostly based on the number of fingers we have or the number of days in the week. I think if we had 8 fingers and 12 day weeks, that would determine most of the duration of antibiotic therapy. That being said, for CAP that is doing well clinically (afebrile, WBC normal, etc) 3 or 4 days of antibiotics is all that is needed, so saith the guidelines. Even severe CAP probably only needs 7 days of therapy (Ref).
Five days likely sufficient for most non-ventilator hospital-acquired pneumonia.
Despite the guidelines that suggest 5 days is all most people need, at least 70% will get an extended duration they do not need. How long. 10 days of course. People just can't resist the allure of counting fingers and basing the antibiotic duration on the result (PubMed).
Hospitalized mild pneumonia (low CURB65 score) can be treated with 5 days (PubMed).
In a meta-analysis, (PubMed) mild to moderate disease, 5 days total therapy is probably enough. The guidelines suggest at least 7 days for CAP from MRSA and Pseudomonas.
Even if bacteremia with S. pneumoniae, it clinically stable ("cough and shortness of breath are improving, the patient is afebrile for at least 8 hours, the white blood cell count is normalizing, and oral intake and gastrointestinal tract absorption are adequate"), it is safe to change to oral (PubMed). 5 days of levofloxacin is as good as 10 days.
The only disease that has probably not been treated with steroids is Cushing's, and CAP is no exception. In a Lancet study, 5 mg a day for 4 days decreased the length of hospitalization in nonimmunocompromised patients by one day, but did not alter short term morbidity or mortality. Would I recommend it? Naw. The steroid group had more hyperglycemia and readmission (PubMed). I would be more interested if dexamethasone decreased long term mortality. Then again, 7 days of prednisone also shortens illness without increasing mortality (PubMed). A 2015 meta-analysis suggests " For hospitalized adults with CAP, systemic corticosteroid therapy may reduce mortality by approximately 3%, need for mechanical ventilation by approximately 5%, and hospital stay by approximately 1 day" (PubMed). Another suggests "Corticosteroids treatment was associated with a decreased risk of adult respiratory distress syndrome (RR, 0.21; 95% CI, 0.080.59), and may reduce the lengths of the hospital and intensive care unit stay, the duration of intravenous antibiotic treatment, and the time to clinical stability. Corticosteroid was not associated with increased rates of adverse events (PubMed)." For me giving steroids for CAP is an unnatural act and it is harder and harder to change as I age.
Fine Risk Class III/IV CAP.
If the pneumonia severity score is less than 110, they only need 3 days of IV and need NOT go home on oral (PubMed). But no one will do this.
If the pneumonia severity score is class IV or V (severe) and patient stable (defined as respiratory rate <25/min, oxygen saturation >90% or arterial oxygen pressure >55 mm Hg, hemodynamically stable, >1°C decrease in temperature in case of fever, absence of mental confusion, and the ability to take oral drugs) can change to oral therapy after 3 days (PubMed).
Regardless, when the patient is afebrile and vital signs are stable, time for discharge. It is way stupid to watch them on po for 24 hours as pharmacokinetically they are on iv four half-lives, usually a day. And it is safe to do (PubMed).
If the cultures are negative I always recommend they be sent home on doxycycline or amoxicillin. as the vast majority of patients are cured at the time of discharge and the last thing they need is a prescription for an expensive quinolone or macrolide.
CAP requiring Intensive Care Unit:
Besides antibiotics, pneumonia should maybe perhaps receive hydrocortisone 200 mg bolus followed by 10mg/hr for 4 days. It decreases mortality (PubMed).
The patient should receive a macrolide for its immunomodulatory effects whether or not the organism is susceptible to a macrolide; it decreases mortality (PubMed).
Pseudomonas infection is not an issue: cefotaxime or ceftriaxone or ampicillin-sulbactam (hah, a drug I still this is a Yugo: underpowered and overpriced) PLUS either erythromycin, azithromycin, clarithromycin or moxifloxacin, levofloxacin, or gemifloxacin.
Pseudomonas infection is not an issue but the patient has a beta-lactam allergy: moxifloxacin, levofloxacin, or gemifloxacin, with or without clindamycin.
Clarithromycin, perhaps due to immunomodulatory effects (PubMed), at a dose of 1 gm a day for three days markedly decreases days on the ventilator and may decrease mortality (PubMed).
Pseudomonas infection may be an issue
Either an antipseudomonal agent plus ciprofloxacin, OR an antipseudomonal agent plus moxifloxacin, levofloxacin, OR erythromycin, azithromycin, clarithromycin.
Pseudomonas infection is an issue but the patient has a beta-lactam allergy: Either aztreonam PLUS levofloxacin (I prefer ciprofloxacin) OR aztreonam PLUS moxifloxacin, or ciprofloxacin. How long to treat? Most of the time 8 days of IV (PubMed).
Hospital-Acquired or Ventilator Acquired Pneumonia: (cefepime or ceftazidime OR imipenem or meropenem OR piperacillin /tazobactam) PLUS linezolid or vancomycin (if worried about MRSA, and who isn't) PLUS (azithromycin or a quinolone (if worried about Legionella). Clarithromycin, perhaps due to immunomodulatory effects at a dose of 1 gm a day for three days markedly decreases days on the vent and may decrease mortality (PubMed).
As of 2019, the Concept of healthcare-associated pneumonia was abandoned in place of "Emphasis on local epidemiology and validated risk factors to determine need for MRSA or P. aeruginosa coverage. Increased emphasis on deescalation of treatment if cultures are negative." About time. It was a stupid concept and led to the overuse of antibiotics.
There is an oh so stupid 'rule' in medicine: once antibiotics are started they can't be stopped and once a class of antibiotics is started, it can't be changed. I call shenanigans. De-escalation of antibiotics is reasonable and safe. You can change from multiple antibiotics to a single antibiotic if Pseudomonas aeruginosa is not present (and most of the time you do not need to two antibiotics for Pseudomonas), shorten the therapy to < 5 days if the cultures are negative and there have been > 48 hours of defervescence, and change from a broad to a narrow antibiotic based on culture data
How long to treat? Most of the time 8 days of IV (PubMed, PubMed). However, and pay attention here, if the CPIS score on day three is < 6, antibiotics can be discontinued as the patient probably doesn't have pneumonia. Click here to calculate a CPIS score.
1-3 days antibiotics are long enough in suspected VAP if "daily minimum PEEP of ≤5 cm H2O and daily minimum FiO2 less than 40% for at least 3 days from the first day of antibiotics (and) may be suitable candidates for early antibiotic discontinuation" (PubMed).
You can also drop the vancomycin if cultures negative, and/or, if you do not have cultures if the nasal swab for MRSA is negative (PubMed) and the CPIS is less than 6 (PubMed). Stopping the anti-MRSA antibiotic in culture-negative patients does not change mortality but is associated with a shorter hospital LOS and lower incidence of AKI (PubMed).
And a curious literature, like Alice's curiouser and curiouser, that adjunctive (Pubmed) clarithromycin for three days decreases mortality. This is not the only study to show such a benefit and perhaps has more to do with the immunomodulatory effects of clarithromycin than its antibacterial effects (Pubmed).
Nursing Home Receiving treatment in a nursing home: moxifloxacin, levofloxacin, or gemifloxacin alone or amoxicillin-clavulanate PLUS erythromycin, azithromycin or clarithromycin.
Hospitalized Nursing Home Patient: Same as for medical ward and ICU.
Pearls
Not all patients have a fever: "Bacteremic pneumonia was present in ... 101 of 2149 (4.7%) afebrile patients" and increased risk of death (Pubmed).
Why is the patient still febrile after antibiotics? From the 2014 NEJM Review:
- Correct organism but inappropriate antibiotic choice or dose
- Resistance of organism to selected antibiotic
- Wrong dose (e.g., in a patient who is morbidly obese or has fluid overload)
- Antibiotics not administered
- Correct organism and correct antibiotic but infection is loculated (e.g., most commonly empyema)
- Obstruction (e.g., lung cancer, foreign body)
- Incorrect identification of causative organism
- No identification of causative organism and empirical therapy directed toward wrong organism
- Noninfectious cause
- Drug-induced fever
- Presence of an unrecognized, concurrent infection
Older patients will often not recover completely, having accelerated functional decline (PubMed). To quote another article (PubMed): "A year after hospitalization for community-acquired pneumonia, moderate-to-severe impairment in multiple cognitive domains affected one-third of patients ≥ 65 years old and 20% of younger patients, and another third of survivors had mild cognitive impairment." Infections are short term and long term bad for people.
Antibiotics do little for acute asthma except for increase cost and hospitalization (PubMed).
Cardiac events are common with CAP and more than doubles mortality (PubMed). The risk of MI goes up with acute viral pneumonias as well. Influenza > RSV > other viri (PubMed), especially during the first week of infection. There is a "small but strongly significant associations in the timing of respiratory infection (with HMPV, RSV, influenza, rhinovirus, and adenovirus) and MI or ischemic stroke hospitalizations in the elderly (PubMed)."
Even if they survive their CAP, and most should, the risk of death is increased for a year after CAP and that death risk is increased for a decade after Pneumococcal pneumonia. Infections are bad for you (PubMed).
One third will have a cardiovascular event and it will increase mortality 5x (PubMed). Amongst other complications, CAP is associated with an increased risk of CHF in the following year (PubMed).
Mortality from Pneumococcal pneumonia has not improved in 20 years despite all the hotshot interventions we have tried (PubMed).
Pleural effusions at admission are a risk for death and have a longer hospital stay (if they live)(Pubmed).
As for so many infections, prior use of NSAIDS increases like likelihood of badness compared to those who did not take NSAIDs: "pleural empyema and lung cavitation (37.5% vs. 7%; ) and had a trend to more invasive disease, with a higher frequency of pleural empyema (25% vs. 5%, P=0.014) and bacteremia (PubMed)."
Could try selective oropharyngeal decontamination with topical application of tobramycin, colistin, and amphotericin B in the oropharynx and stomach for four days. Decreased mortality at 30 days by 2.9% (PubMed). Overall, I am not a fan.
Room air O2 saturation in CAP of < 92% have increased morbidity and mortality (PubMed).
If you should have to resort to colistin, adding inhaled to iv adds nothing for the treatment (PubMed).
There is always the urge to add inhaled antibiotics. A 2016 meta-analysis suggests "There is insufficient evidence for the use of inhaled antibiotic therapy as primary or adjuvant treatment of VAP or VAT" (PubMed). Not that insufficient evidence ever stops anyone. Hell sufficient evidence shows acupuncture is nothing but placebo and people keep on using it.
For severe pneumonia, one meta-analysis suggests zinc supplementation will decrease mortality (PubMed).
Rants
I tend to go on and on that infections are inflammatory, that inflammation is prothrombotic, and that every infection that has been evaluated has an increase in vascular events (stroke, MI or PE) in the months following the infection. It may be why people with hospitalized infections have higher death rates. But it is like the weather. Everyone complains about it but no one tries to change it.
Well, now you can. 300 mg of aspirin a day for a month decreased cardiac events and deaths in patients with pneumonia (PubMed). I suspect that in a decade, once the clinical trials are complete, that everyone with an acute infection will go home on ASA.
But. NSAIDs during an acute respiratory infection increase MI risk 3.4x (PubMed).
What continues to flabber my gaster is how people order tests then ignore them For pneumonia a negative procalcitonin combined with a costive viral PCR does not result in antibiotics being stopped (PubMed).
Curious Cases
Relevant links to my Medscape blog
One More Thing I Do Not Miss From the Old Days
I'll show, you tell. Part one.
Searching for something to write about
I got nothing. Which is something
Last Update: 01/30/20.