Preferred high-dose, oral drug of choice for pneumococcal infections once etiology established. Dosing up to 4g per day provides serum concentrations to inhibit isolates with MIC as high as 2. Lacks activity against atypical agents and nearly half of H. influenzae infections.
Preferred high-dose, has all features of amoxicillin and reliable activity against H. influenzae, but more expensive. New XR formulation (1000/62.5 mg) allows increase in amoxicillin dose to 2000 twice daily to inhibit pneumococci with MIC as high as 2 mcg/mL without increasing the dose of clavulanate (125 mg twice daily), the diarrhea-causing component.
Good activity against S. pneumoniae and H. influenzae but lacks atypical activity and activity vs. P. aeruginosa. Third-generation cephalosporins are favored over parenteral beta-lactams for empiric therapy unless aspiration suspected.
Has activity against all major pathogens causing CAP in immunocompetent pts, except P. aeruginosa, and has proven efficacy as monotherapy. Major advantages are convenience of once daily dosing and the tissue pharmacokinetics, which permit shorter duration of therapy. Up to 35% of pneumococci are resistant in vitro, but clinical significance of low-level resistance (MIC ≤ 8) is debated. Clarithromycin may have better PK profile, but may not be as well tolerated.
Not recommended, given low potency against S. pneumoniae and lack of atypical activity.
Adds pseudomonal activity to spectrum of third-generation cephalosporins, so most useful when P. aeruginosa suspected or confirmed. Should be paired with macrolide when used empirically due to lack of activity against atypical pathogens.
With ceftriaxone, the parenteral beta-lactam of choice for empiric therapy unless aspiration or P. aeruginosa suspected. Should be combined with a macrolide or FQ in seriously ill pts.
"Fifth generation cephalosporin" with broader spectrum activity including MRSA due to addition of the 1,3-thiazole ring moiety. FDA approved for community acquired pneumonia and skin and soft tissue infections.
Third-generation cephalosporin with enhanced activity against P. aeruginosa, but reduced activity against S. pneumoniae, H. influenzae compared to ceftriaxone, cefotaxime. Use should be limited to suspected or confirmed pseudomonal pneumonia.
Alternative treatment with cefprozil, cefpodoxime and cefditoren, these are the oral cephalosporins of choice. Cefuroxime should generally not be used parenterally for empiric therapy of pneumonia due to poor pharmacodynamic target attainment against pneumococci relative to third-generation cephalosporins.
Like azithromycin has activity against all major pathogens in immunocompetent pts. XL formulations permit once daily oral dosing. Main disadvantage is lack of IV formulation. Up to 35% of pneumococci are resistant in vitro, but clinical significance of low-level resistance (MIC < 8) is debated. Has best PK profile of macrolides, but may not be as well tolerated as azithromycin.
Treatment of choice for aspiration pneumonia, but may also be useful against multi-drug resistant pneumococci (resistance rates < 10%) and against MRSA. For the latter however, must rule out inducible clindamycin resistance with a D-test if isolate is erythromycin-resistant.
Do not use to treat pneumonia. Shown to be inferior to ceftriaxone in clinical trial of CAP treatment, presumably because it achieves low concentrations in broncho-alveolar lining fluid and may be bound to pulmonary surfactant.
A rational choice for outpts due to activity against all major pathogens of CAP in immunocompetent pts. Resistance rates vary among pneumococci, but are generally less than 20%.
Preferred treatment has activity against all major pathogens of bacterial pneumonia and advantages of once-daily dosing and high oral bioavailability. Avoid empiric use in pts recently treated with a FQ. Although ciprofloxacin remains the FQ of choice for pseudomonal infections, the 750 mg daily dose of levofloxacin likely has similar activity.
Reliable activity against all Gram-positive bacteria and excellent oral bioavailability, but no activity against Gram-negative or atypical pathogens. Very expensive. RCT of linezolid versus vancomycin found greater clinical efficacy, but numbers were insufficient to evaluate isolates with vancomycin MICs >1mcg/mL. Probably the preferred agent against strains with vancomycin MICs >1 mcg/ml. Use should generally be limited to MRSA pneumonia, especially when oral therapy is preferred and other drugs (TMP-SMX, clindamycin, FQ) are not options.
Preferred treatment has activity against all major pathogens of bacterial pneumonia and has advantages of once daily dosing and high oral bioavailability. Avoid empiric use in pts recently treated with a FQ. Ciprofloxacin remains the FQ of choice for pseudomonal infections.
Omadacycline is a semisynthetic aminomethylcycline with activity against MRSA, penicillin- and multidrug-resistant S. penumoniae, S. pyogenes, S. agalactiae, and VRE. It can overcome tetracycline resistance by circumventing ribosomal protection proteins and active efflux pumps.
Broad-spectrum beta-lactam most useful when infection with P. aeruginosa suspected or confirmed. May be used without the tazobactam if susceptibility confirmed.
New ketolide that is active against virtually all S. pneumoniae, including macrolide-resistant isolates. Unusual side effect is impaired visual accommodation. Avoid in pts on PIs, as it may interact adversely. Concern for risk of fulminant hepatic failure prompted FDA to remove indication for acute sinusitis and AECB.
Trimethoprim + Sulfamethoxazole
Unreliable activity vs. S. pneumoniae and H. influenzae make this a poor empiric choice for CAP, but it remains treatment of choice for PCP and should be added when PCP suspected. Has also become an option for MRSA infections.
Predictable activity against virtually all S. pneumoniae and S. aureus strains, but limited activity against other common CAP pathogens. Little rationale for use in empiric treatment of pneumonia unless MRSA suspected. Emerging evidence suggests vancomycin has poor activity against MRSA strains with MICs >1 mcg/ml. Consider use of linezolid for pneumonia caused by such strains.
Broad-spectrum tetracycline derivative active against resistant MRSA, drug-resistant pneumococcus, ESBL+ bacilli, some multidrug-resistant Acinetobacter, anaerobes, and atypicals. Not active against P. aeruginosa. Non-inferior to levofloxacin in immunocompetent patients with CAP, however given its extremely broad-spectrum and lack of oral formulation, its use should be restricted to pathogen-directed therapy for resistant organisms in hospitalized patients when other options are not available.
Cephalosporin (ceftriaxone, cefotaxime, cefpodoxime, cefprozil, cefditoren, cefuroxime axetil, cefdinir), macrolide (azithro, clarithromycin), FQ (moxifloxacin, levofloxacin, gemifloxacin), clindamycin, doxycycline, telithromycin
Clarithromycin (no IV form), doxycycline, ciprofloxacin
Staphylococcus aureus-methicillin suspect.
Oxacillin, nafcillin, cefazolin
Clindamycin, TMP/SMX, vancomycin,
Staphylococcus aureus-methicillin resist.
Clindamycin, TMP/SMX, minocycline, doxycycline or tigecycline, quinupristin/dalfopristin. AVOID DAPTOMYCIN
Beta-lactam (ceftazidime, cefepime, piperacillin +/- tazobactam, ticarcillin +/- clavulanate, carbapenem, aztreonam) PLUS tobramycin
Beta-lactam plus gentamicin, Beta-lactam plus ciprofloxacin or levofloxacin 750mg
Clindamycin, beta-lactam/beta-lactamase inhibitor
PCN plus metronidazole, carbapenem, moxifloxacin
FQ (gatifloxacin, moxifloxacin, levofloxacin, gemifloxacin)
FQ (gatifloxacin, moxifloxacin, levofloxacin, gemifloxacin)
Minocycline (non-severe), carbapenem + amikacin (severe)
Comment: 2019 guidelines recommend sputum and blood culture in all patients treated empirically for MRSA and P. aeruginosa as well as those hospitalized with severe pneumonia. Increased yield for pathogens serves as the rationale for recommending Gram stain and culture after intubation. β-lactam/macrolide combination is preferred and supported by stronger evidence, whereas 2007 guidelines gave equal weight to β-lactam/macrolide and β-lactam/fluoroquinolone for standard empiric therapy for severe CAP. Guidelines do not recommend routine use of procalcitonin, steroids, or follow-up chest imaging.
Comment: Updated comment on bacterial pneumonia in HIV+ patients includes treatment recommendations.
Comment: Dutch incidence rates of community-aquired pneumonia (CAP) and invasive pneumococcal disease (IPD) from 2008 to 2017 amounted to 111 and 1529 per 100,000 PY. Both occurred more often in those with CD4 < 500; however, incidence rates remained higher in those with CD4 > 500 when compared to general population (946 vs 188 per 100,000 PY). All cases of IPD were vaccine serotypes. Case fatality rate for IPD was 8% and for CAP was 4%. Authors recommend vaccination.
Comment: Results of a multiplex PCR pneumonia panel, which identifies 15 bacteria, 3 atypcial bacteria, 8 viruses, and 7 antimicrobial resistance genes within 1 hour, were compared to results of conventional cultures read at 18-24 hours, held for 2 days, and analyzed by a MALDI-TOF MS system. Other testing included: direct immunofluorescence staining for viruses and Chlamydia, serum IgM and IgG for M. pneumoniae, urine specimens for Legionella and pneumococcal antigen, and fluorescent immunoassay for influenza A and B. Authors attribute most discordance to antibiotic use prior to sampling and note that molecular diagnostics do not distinguish colonization from infection. Coinfections were documented in 42% of 59 specimens.
Comment: A population-based surveillance study from 2008-2018, identified adults ≥18 years with invasive non-typeable H. influenzae. Of those with infections from 2017-2018 (n = 179), persons with HIV (n = 31) were more likely than those from 2008-2018 without HIV (n = 124) to be male (94% vs 49%), black (100% vs 53%), and have septic arthritis (35% vs 1%).
Comment: The Veterans Aging Cohort Study studied nearly 42,000 HIV+ veterans followed from 1996-2009 and found an association between COPD and community-acquired pneumonia (IRR, 1.9; 95%CI, 1.6-2.3).
Comment: Retrospective study of 9,101 HIV+ individuals admitted to urban, teritary St. Luke’s-Roosevelt Hospital Center, identified 237 deaths from 2004 to 2008. In chart review of 208 cases, mortality due to AIDS-related illnesses was associated with younger age (44 vs 50 yrs, p = 0.001), women (45 vs 25 %, p = 0.013), and lower CD4+ T cell counts (10 vs 66, p = 0.001). Cause of death was categorized as sepsis (35%), bacterial pneumonia (20%), cardiac disease (6%), liver disease (4%), and non-AIDS-related malignancy (4%).
Comment: Meta-analysis of 8 pooled cohort studies found current smokers versus current non-smokers at higher risk for bacterial pneumonia (RR, 1.7, 95%CI, 1.4-2.1) and concluded that smoking cessation may mitigate this risk.
Comment: RCT of 348 hospitalized patients with MRSA nosocomial pneumonia treated with linezolid (N=172) versus vancomycin (N=176) in per protocol analysis 58% versus 47% achieved "clinical success" at end of study (p=0.042), 60-day mortality was 16% versus 17%, respectively.
Comment: Danish nationwide population-based cohort study of first-time hospitalization to treat pneumonia (excluding AIDS-defining PCP) included 3,516 HIV+ and 328,738 HIV- individuals followed from 1995-2007 documented decline in incidence rate ratios for those HIV+ from 35 (95%CI, 28-42) in 1995-1996 to 6 (95%CI, 5-8) in 2005-2007. Risk factors for increased risk of pneumonia were IV drug use, low CD4, nadir CD4, older age, and absence of ART.
Comment: Recommendations for management of immunocompetent pts, information on laboratory testing, Abx selection and the role of specific pathogens.
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