What are the most common causes of CAP? Although pneumococcus remains the most commonly identified cause of CAP, the frequency with which it is implicated has declined, and it is now detected in only about 10 to 15% of inpatient cases in the United States. Other bacteria that cause CAP include Haemophilus influenzae, Staphylococcus aureus, Moraxella catarrhalis, Pseudomonas aeruginosa, and other gram-negative bacilli. Patients with chronic obstructive pulmonary disease (COPD) are at increased risk for CAP caused by H. influenzae and Mor. catarrhalis. P. aeruginosa and other gram-negative bacilli also cause CAP in persons who have COPD or bronchiectasis, especially in those taking glucocorticoids. There is a wide variation in the reported incidence of CAP caused by Mycoplasma pneumoniae and Chlamydophila pneumoniae (so-called atypical bacterial causes of CAP), depending in part on the diagnostic techniques that are used. During influenza outbreaks, the circulating influenza virus becomes the principal cause of CAP that is serious enough to require hospitalization, with secondary bacterial infection as a major contributor.
What evaluation do the authors recommend to determine the cause of community-acquired pneumonia in a hospitalized patient? In hospitalized patients with CAP, the authors favor obtaining Gram’s staining and culture of sputum, blood cultures, testing for legionella and pneumococcal urinary antigens, and multiplex PCR assays for Myc. pneumoniae, Chl. pneumoniae, and respiratory viruses, as well as other testing as indicated in patients with specific risk factors or exposures. A low serum procalcitonin concentration (<0.1 µg per liter) can help to support a decision to withhold or discontinue antibiotics. Results on Gram’s staining and culture of sputum are positive in more than 80% of cases of pneumococcal pneumonia when a good-quality specimen (>10 inflammatory cells per epithelial cell) can be obtained before, or within 6 to 12 hours after, the initiation of antibiotics. Blood cultures are positive in about 20 to 25% of inpatients with pneumococcal pneumonia but in fewer cases of pneumonia caused by H. influenzae or P. aeruginosa and only rarely in cases caused by Mor. catarrhalis.
What are the guidelines for treating community-acquired pneumonia in outpatients and inpatients? For outpatients without coexisting illnesses or recent use of antimicrobial agents, IDSA/ATS [Infectious Diseases Society of America and the American Thoracic Society] guidelines recommend the administration of a macrolide (provided that <25% of pneumococci in the community have high-level macrolide resistance) or doxycycline. For outpatients with coexisting illnesses or recent use of antimicrobial agents, the guidelines recommend the use of levofloxacin or moxifloxacin alone or a beta-lactam (e.g., amoxicillin–clavulanate) plus a macrolide. The authors argue, however, that a beta-lactam may be favored as empirical therapy for CAP in outpatients, since most clinicians do not know the level of pneumococcal resistance in their communities, and Str. pneumoniae is more susceptible to penicillins than to macrolides or doxycycline. Even though the prevalence of Str. pneumoniae as a cause of CAP has decreased, they raise concern about treating a patient with a macrolide or doxycycline to which 15 to 30% of strains of Str. pneumoniae are resistant. For patients with CAP who require hospitalization and in whom no cause of infection is immediately apparent, IDSA/ATS guidelines recommend empirical therapy with either a beta-lactam plus a macrolide or a quinolone alone.
What is the appropriate duration of antibiotic therapy for community-acquired pneumonia? Early in the antibiotic era, pneumonia was treated for about 5 days; the standard duration of treatment later evolved to 5 to 7 days. A meta-analysis of studies comparing treatment durations of 7 days or less with durations of 8 days or more showed no differences in outcomes, and prospective studies have shown that 5 days of therapy are as effective as 10 days and 3 days are as effective as 8. Nevertheless, practitioners have gradually increased the duration of treatment for CAP to 10 to 14 days. The authors argue that a responsible approach to balancing antibiotic stewardship with concern about insufficient antibiotic therapy would be to limit treatment to 5 to 7 days, especially in outpatients or in inpatients who have a prompt response to therapy. Pneumonia that is caused by Staph. aureus or gram-negative bacilli tends to be destructive, and concern that small abscesses may be present has led clinicians to use more prolonged therapy, depending on the presence or absence of coexisting illnesses and the response to therapy.
- Strep pneumo still is the most common bug, and is more sensitive to penicillins than macrolides or doxy.
- Uncomplicated, outpatient treatment: Macrolide or Doxy, consider adding a beta-lactam if high risk; alternatively, respiratory quinolone by it self.
- Sputum gram stain and cultures.. maybe, don't expect to get too much from them.
- 5 days of treatment is as good as 10.
Thursday, October 23, 2014
One of the oldest (and deadliest) diseases in history, pneumonia continues being a threat. Recognizing and treating properly are the best way to minimize complications. Another good review from this week's NEJM.
Friday, October 10, 2014
This has been one of those topics that give me a headache. However, having a simple approach is very helpful. This week's NEJM (Oct 9th) has an interesting review. Here are the Q&A on this topic.
What are some uses and limitations of the anion gap?
Lactic acidosis accounts for about half of the high anion gap cases, and is often due to shock or tissue hypoxia. The anion gap however, is a relatively insensitive reflection of lactic acidosis — roughly half the patients with serum lactate levels between 3.0 and 5.0 mmol per liter have an anion gap within the reference range. With a sensitivity and specificity below 80% in identifying elevated lactate levels, the anion gap cannot replace a serum lactate measurement. Nevertheless, lactate levels are not routinely drawn or always rapidly available, and a high anion gap can alert the physician that further evaluation is necessary. In addition, the anion gap should always be adjusted for the albumin concentration, because this weak acid may account for up to 75% of the anion gap. Without correction for hypoalbuminemia, the anion gap can fail to detect the presence of a clinically significant increase in anions (>5 mmol per liter) in more than 50% of cases. For every 1 g per deciliter decrement in serum albumin concentration, the calculated anion gap should be raised by approximately 2.3 to 2.5 mmol per liter.
What are the characteristics of a normal anion-gap (hyperchloremic) acidosis?
Chloride plays a central role in intracellular and extracellular acid–base regulation. A normal anion-gap acidosis will be found when the decrease in bicarbonate ions corresponds with an increase in chloride ions to retain electroneutrality, also called a hyperchloremic metabolic acidosis. This type of acidosis occurs from gastrointestinal loss of bicarbonate (e.g., because of diarrhea or ureteral diversion), from renal loss of bicarbonate that may occur in defective urinary acidification by the renal tubules (renal tubular acidosis), or in early renal failure when acid excretion is impaired. Hospital-acquired hyperchloremic acidosis is usually caused by the infusion of large volumes of normal saline (0.9%). Hyperchloremic acidosis should lead to increased renal excretion of ammonium, and measurement of urinary ammonium can therefore be used to differentiate between renal and extrarenal causes of normal anion-gap acidosis. However, since urinary ammonium is seldom measured, the urinary anion gap and urinary osmolal gap are often used as surrogate measures of excretion of urinary ammonium. The urine anion gap ([Na+] + [K+] – Cl–]) is usually negative in normal anion-gap acidosis, but it will become positive when excretion of urinary ammonium (NH4+) (as ammonium chloride [NH4Cl]) is impaired, as in renal failure, distal renal tubular acidosis, or hypoaldosteronism.
What is a useful approach to the analysis and treatment of a metabolic alkalosis?
The normal kidney is highly efficient at excreting large amounts of bicarbonate, and accordingly, the generation of metabolic alkalosis requires both an increase in alkali and impairment in renal excretion of bicarbonate. Gastric fluid loss and diuretic use account for the majority of metabolic alkalosis cases. By measuring chloride in urine, one can distinguish between chloride-responsive and chloride-resistant metabolic alkalosis. If the kidneys perceive a reduced “effective circulating volume,” they avidly reabsorb filtered sodium, bicarbonate, and chloride, largely through activation of the renin–angiotensin–aldosterone system, thus reducing the concentration of urinary chloride. A (spot sample) urinary chloride concentration of less than 25 mmol per liter is reflective of chloride-responsive metabolic alkalosis. Administration of fluids with sodium chloride (usually with potassium chloride) restores effective arterial volume, replenishes potassium ions, or both with correction of metabolic alkalosis. Metabolic alkalosis with a urinary chloride concentration of more than 40 mmol per liter is mainly caused by inappropriate renal excretion of sodium chloride, often reflecting mineralocorticoid excess or severe hypokalemia (potassium concentration <2 mmol per liter). The administration of sodium chloride does not correct this type of metabolic alkalosis, which, for that reason, is called “chloride-resistant.” Diuretic-induced metabolic alkalosis is an exception because the concentration of chloride in urine may increase initially, until the diuretic effect wanes, after which the concentration of chloride in the urine will fall below 25 mmol per liter.
How is the “delta anion gap” helpful in the evaluation of mixed metabolic acid–base disorders?
In high anion-gap metabolic acidosis, the magnitude of the anion gap increase (delta AG, or ΔAG) is related to the decrease in the bicarbonate ions (Δ[HCO3–]). To diagnose a high anion-gap acidosis with concomitant metabolic alkalosis or normal anion-gap acidosis, the so-called delta-delta (Δ-Δ) may be used. The delta gap is the comparison between the increase (delta) in the anion gap above the upper reference value (e.g., 12 mmol per liter) and the change (delta) in the concentration of bicarbonate ions from the lower reference value of bicarbonate ions (e.g., 24 mmol per liter). In ketoacidosis, there is a 1:1 correlation between the rise in anion-gap and the fall in concentration of bicarbonate. In lactic acidosis, the decrease in concentration of bicarbonate is 0.6 times the increase in anion gap (e.g., if the anion gap raises 10 mmol per liter, the concentration of bicarbonate should decrease about 6.0 mmol per liter). This difference is probably due to the lower renal clearance of lactate compared with keto-anions. Hydrogen buffering in cells and bone takes time to reach completion. Accordingly, the ratio may be close to 1:1 with “very acute” lactic acidosis (as with seizures or exercise to exhaustion). If the ΔAG – Δ[HCO3–] in ketoacidosis or if 0.6 ΔAG – Δ[HCO3–] in lactic acidosis = 0±5 mmol per liter, simple anion-gap metabolic acidosis is present. A difference greater than 5 mmol per liter suggests a concomitant metabolic alkalosis, and if the difference is less than –5 mmol per liter, a concomitant normal anion-gap metabolic acidosis is diagnosed.