Is treatment of pneumococcal pneumonia with bacteremia any different than pneumococcal pneumonia without bacteremia?

In the absence of disseminated infection such as meningitis or endocarditis, there is no convincing evidence that bacteremic pneumococcal pneumonia (BPP) requires either longer course of IV or oral antibiotics. In fact, although previously thought to have a worse prognosis, recent data have failed to demonstrate any difference in time to clinical stability, duration of hospital stay or community-associated pneumonia (CAP)-related mortality with BPP when other factors such as patient comorbidities and severity of disease are also considered1,2

Although many patients with CAP receive 7-10 days of antibiotic therapy, shorter durations as little as 5 days may also be effective3,4.  Generally, once patients with BPP have stabilized on parenteral therapy, a switch to an appropriate oral antibiotic (eg, a β-lactam or a respiratory quinolone such as levofloxacin) can be made safely5.  Although large randomized-controlled studies of treatment of BPP are not available, a cumulative clinical trial experience with levofloxacin for patients with BPP reported a successful clinical response in >90% of patients (median duration of therapy 14 d)6. Resistance to levofloxacin and failure of treatment in pneumococcal pneumonia (with or without bacteremia), however, has been rarely reported7.

 

References

  1. Bordon J, Peyrani P, Brock GN. The presence of pneumococcal bacteremia does not influence clinical outcomes in patients with community-acquired pneumonia. Chest 2008;133;618-624.
  2. Cilloniz C, Torres A. Understanding mortality in bacteremic pneumococcal pneumonia. J Bras Pneumol 2012;38:419-421.
  3. Mandell LA, Wunderink RG, Anzueto A, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis 2007;44:S27-72.
  4. Shorr F, Khashab MM, Xiang JX, et al. Levofloxacin 750-mg for 5 days for the treatment of hospitalized Fine Risk Class III/IV community-acquired pneumonia patients. Resp Med 2006;100:2129-36.
  5. Ramirez JA, Bordon J. Early switch from intravenous to oral antibiotics in hospitalized patients with bacteremic community-acquired Streptococcus pneumonia pneumonia. Arch Intern Med 2001;161:848-50.
  6. Kahn JB, Bahal N, Wiesinger BA, et al. Cumulative clinical trial experience with levofloxacin for patients with community-acquired pneumonia-associated pneumococcal bacteremia. Clin Infect Dis 2004;38(supp 1):S34-42.
  7. Davidson R, Cavalcanti R, Brunton JL, et al. Resistance to levofloxacin and failure of treatment of pneumococcal pneumonia. N Engl J Med 2002;346:747-50.
Is treatment of pneumococcal pneumonia with bacteremia any different than pneumococcal pneumonia without bacteremia?

How does azithromycin (AZ) benefit patients with severe COPD or cystic fibrosis (CF)?

AZ is a macrolide antibiotic which interferes with bacterial protein synthesis by binding to the 50S ribosomal subunit. It is often used to treat acute respiratory tract infections due to Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, as well as Mycoplasma, Chlamydia, and Legionella sp1. Although it has no in vitro activity against many aerobic gram-negative bacilli such as Pseudomonas aeruginosa, its chronic use has often been associated with a significant reduction in the frequency of disease exacerbations in patients with chronic bronchiectasis and colonization due to this organism, including patients with COPD or CF1-3.

Because P. aeruginosa is invariably macrolide-resistant, the beneficial effect of AZ in chronically infected or colonized patients must be due to factors other than its direct effect on bacterial replication.  Several mechanisms have been invoked including: 1. Inhibition of quorum-sensing dependent virulence factor and biofilm production 2.Blunting of host inflammatory response (eg, ↑IL-10, and ↓ IL-1ß, IL-6, IL-8, TNF-α, and ↓ chemotaxis); and 3. Enhanced antiviral response1.

The latter finding is quite unexpected but AZ appears to augment interferon response to rhinovirus in bronchial cells of COPD patients3.  With respiratory viruses (including rhinoviruses) causing 20-55% of all COPD exacerbations, perhaps this is another way AZ may help the host! Who would have thought!!

References

  1. Vos R, Vanaudenaerde BM, Verleden SE, et al. Anti-inflammatory and immunomodulatory properties of azithromycin involved in treatment and prevention of chronic lung allograft rejection. Transplantation 2012;94:101-109.
  2. Cochrane review. Treatment with macrolide antibiotics for people with cystic fibrosis and chronic chest infection. Nov 14, 2012. http://www.cochrane.org/CD002203/CF_treatment-with-macrolide-antibiotics-for-people-with-cystic-fibrosis-and-chronic-chest-infection
  3. Menzel M, Akbarshahi H, Bjermer L, et al. Azithromycin induces anti-viral effects in cultured bronchial epithelial cells from COPD. Scientific Reports 2016; 6:28698. DOI:10.1038/srep 28698.
How does azithromycin (AZ) benefit patients with severe COPD or cystic fibrosis (CF)?

Routine screening of my patient suspected of having tuberculosis (TB) shows that he is HIV seropositive. Does HIV affect the clinical manifestation of TB?

Patients with newly-diagnosed TB are ~20 times more likely to be coinfected with HIV than those without TB. Unfortunately, the diagnosis of TB in HIV-infected patients is often delayed in part related to its atypical presentation1.

In HIV-infected patients with high CD4 counts, clinical manifestations of TB are usually similar to those without HIV infection (eg, subacute fever, weight loss, cough) with CXR often showing upper lobe infiltrates and/or cavitations typically seen in reactivation TB.

Lower CD4 counts, however, are associated with atypical CXR findings, including pleural effusions, lower or middle lobe infiltrates, mediastinal adenopathy, and lack of cavitary lesions1,2.  A normal CXR has been reported in 21% of patients with CD4 <200 cells/μl (vs 5% in those with higher counts)2.

Advanced immune suppression in HIV infection is also associated with negative sputum smears for acid-fast bacilli, concurrent extra-pulmonary disease, and immune reconstitution symptoms after initiation of anti-TB therapy1.

 

References

  1. Kwan CK, Ernst JD. HIV and tuberculosis: a deadly human syndemic. Clin Microbiol Rev 2011;24:351-376.
  2. Greenberg, SD, Frager D, Suster B, et al. Active pulmonary tuberculosis in patients with AIDS: spectrum of radiographic findings (including a normal appearance). Radiology 1994;193:115-9.
Routine screening of my patient suspected of having tuberculosis (TB) shows that he is HIV seropositive. Does HIV affect the clinical manifestation of TB?

My patient with significant dyspnea appears to have an acute exacerbation of his chronic obstructive pulmonary disease (AE-COPD). How often do AE-COPD and pulmonary embolism (PE) coexist?

Simultaneous presence of PE in patients with AE-COPD is not rare, particularly in those with unexplained AE-COPD. A recent systematic review and meta-analysis reported a pooled PE prevalence of 16.1% (95% C.I. 8.3%-25.8%) in unexplained AE-COPD, with 68% of emboli found in the main pulmonary arteries, lobar arteries or inter-lobar arteries (i.e. not subsegmental); the pooled prevalence of deep venous thrombosis (DVT) was 10.5% (95% C.I. 4.3%-19.0%) 1. Pleuritic chest pain and signs of cardiac failure were associated with AE-COPD, while symptoms suggestive of a respiratory tract infection argued against PE.

It remains unclear, however, if the threshold for evaluation of venous thromboembolism (VTE) should necessarily differ between patients with explained vs unexplained AE-COPD. In one small study, the prevalence of VTE in “unexplained” AE-COPD was significantly higher (25%) than “explained” AE-COPD (including cases with  tracheobronchitis, pneumonia, cardiac disorders, exposure to irritant inhalants, and lack of compliance with treatment), but the VTE prevalence for the latter group was still 8.4%2.  Serum D-dimer level and Wells criteria may help exclude VTE in this patient population.

References

  1. Aleva FE, Voets LWLM, Simons SO, et al. Prevalence and localization of pulmonary embolism in unexplained acute exacerbations of COPD: A systematic review and meta-analysis. CHEST (2016), doi: 10.1016/j.chest.2016.07.034.
  2. Gunen H, Gulbas G, In E, Yetkin O, Hacievliyagil SS. Venous thromboemboli and exacerbations of COPD. Eur Respir J 2010;35:1243-1248.

 

Contributed by Jeff Greenwald, MD, Core Educator Faculty, Department of Medicine, Massachusetts General Hospital

My patient with significant dyspnea appears to have an acute exacerbation of his chronic obstructive pulmonary disease (AE-COPD). How often do AE-COPD and pulmonary embolism (PE) coexist?

What is the significance of Howell-Jolly bodies (HJBs) in the peripheral smear of my patient with a spleen who presented with a pneumonia?

HJBs (Figure) are named after Henry Howell, an American physiologist who pioneered the use of heparin as an anti-coagulant and Justin Jolly, a French hematologist who filmed mitotic activity in cells. HJBs are nuclear remnants in circulating mature red blood cells which are usually pitted by the spleen under normal physiological conditions. They are often indicative of asplenia (either post-splenectomy or congenital absence) or hyposplenism associated with a variety of conditions, including  sickle cell disease, autoimmune disorders, celiac disease, inflammatory bowel disease, HIV, cirrhosis, primary pulmonary hypertension, splenic irradiation, amyloidosis, sarcoidosis, bone marrow transplantation, and high-dose corticosteroid therapy1-3.

Patients with pneumonia and HJBs on peripheral smear may be hyposplenic and at risk of potentially serious infections, predominantly caused by encapsulated bacteria eg, Streptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitidis3.  Such patients should be immunized against these organisms, including sequential receipt of both conjugated and polysaccharide pneumococcal vaccines3,4.

howelljollymgh

Photo courtesy of Michael S. Abers, MD

 

References

  1. Di Sabatino, A, Carsetti R, Corazza G. Post-splenectomy and hyposplenic states. Lancet 2011;378:86–97.
  2. Brousse, V, Buffet P, Rees D. The spleen and sickle cell disease: the sick(led) spleen. Br J Haematol 2014;166: 165–176.
  3. Mathew H, Dittus C, Malek A, Negroiu A. Howell-Jolly bodies on peripheral smear leading to the diagnosis of congenital hyposplenism in a patient with septic shock. Clin Case Rep 2015;3:714-717.
  4. Kuchar E, Miśkiewicz K , Karlikowska M. A review of guidance on immunization in persons with defective or deficient splenic function. Br J Haematol 2015; 171:683-94. doi: 10.1111/bjh.13660, Epub 2015 Aug 28.

Contributed by Katarzyna Orlewska, Medical Student, Warszawski Uniwersytet Medyczny, Poland

What is the significance of Howell-Jolly bodies (HJBs) in the peripheral smear of my patient with a spleen who presented with a pneumonia?

How should patients with hospital-associated pneumonia (HAP) be empirically treated under the 2016 clinical practice guidelines by the Infectious Diseases Society of America and the American Thoracic Society?

Although empiric selection of antibiotics should be based on the local distribution of pathogens associated with HAP and their antimicrobial susceptibilities, routine coverage of Staphylococcus aureus (not necessarily methicillin-resistant S. aureus [MRSA]) and Pseudomonas aeruginosa or other gram-negative bacilli is recommended1.

In patients not at high risk of mortality (including ventilatory support and septic shock) or risk for MRSA (i.e.prior IV antibiotic use within 90 days, hospitalization in a unit where >20% of S. aureus isolates are MRSA or the prevalence of MRSA is unknown), piperacillin-tazobactam, cefepime, levofloxacin, imipenem or meropenem alone is suggested.

In patients not at high risk of mortality but with factors that increase the likelihood of MRSA, piperacillin-tazobactam, cefepime/ceftazidime, ciprofloxacin/levofloxacin, imipenem/meropenem, or aztreonam, plus vancomycin or linezolid should be considered.

In patients at high risk of mortality or receipt of IV antibiotics during the prior 90 days vancomycin or linezolid plus 2 of the following should be used: piperacillin-tazobactam, cefepime/ceftazidime, ciprofloxacin/levofloxacin, imipenem/meropenem, amikacin/gentamicin/tobramycin, or aztreonam are recommended (avoid double β-lactams).

In patients with structural lung disease increasing the risk of gram-negative infections (ie, bronchiectasis or cystic fibrosis), double anti-pseudomonal coverage is recommended.

 

Reference

  1. Kalil AC, Metersky ML, Klompas M, et al. Management of adults with hospital-acquired and ventilator-associated pneumonia: 2016 clinical practice guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis, Advance Access published July 14, 2016.
How should patients with hospital-associated pneumonia (HAP) be empirically treated under the 2016 clinical practice guidelines by the Infectious Diseases Society of America and the American Thoracic Society?

What are some of the major changes in the 2016 Infectious Diseases Society of America and the American Thoracic Society guidelines on pneumonia in hospitalized patients?

The most noticeable change is the elimination of the concept of health-care associated pneumonia (HCAP) altogether1. This action is in part related to the fact that many patients with HCAP are not at high risk for multi-drug resistant organisms (MDROs) , and that individual patient risk factors, not mere exposure to healthcare facilities, are better determinant of  the need for broader spectrum antimicrobials.

Other noteworthy points in the guidelines include:

  1. Although hospital-associated pneumonia (HAP) is still defined as a pneumonia not incubating at the time of admission and occurring 48 hrs or more following hospitalization, it now only refers to non-VAP cases; VAP cases are considered a separate category.
  2. Emphasis is placed on each hospital generating antibiograms to guide providers with respect to the optimal choice of antibiotics.
  3. Despite lack of supportive evidence, the guidelines recommend obtaining respiratory samples for culture in patients with HAP.
  4. Prior intravenous antibiotic use within 90 days is cited as the only consistent risk factor for MDROs, including methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas sp.

 

Reference

  1. Kalil AC, Metersky ML, Klompas M, et al. Management of adults with hospital-acquired and ventilator-associated pneumonia: 2016 clinical practice guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis, Advance Access published July 14, 2016.
What are some of the major changes in the 2016 Infectious Diseases Society of America and the American Thoracic Society guidelines on pneumonia in hospitalized patients?