Community-acquired pneumonia medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Chetan Lokhande, M.B.B.S [2]; Alejandro Lemor, M.D. [3]

Overview

The mainstay of therapy for community-acquired pneumonia includes antimicrobial therapy and the management of complications. Empiric therapy depends on the age of the patient, severity of disease (inpatient vs. outpatient therapy), and the need for admission to the ICU.

Antibiotic Therapy

• Before initiating therapy the patient should be evaluated according to the following criteria:

1. The level of testing needed to find out the etiology
2. Class of antibiotic to be started
3. Site-of-care decisions (outpatient, inpatient, or intensive care unit)

Major trials of antibiotic prescribing strategies

	Intervention	Comparison	Antibiotic duration (days)
			Intervention group	Control group
ProACT, 2018	Procalciton-guided antibiotics*	IDSA/ATS 2007 guidelines*	4.2	4.3
ProHOSP, 2009	Procalciton-guided antibiotics	Usual care	7	11
Uranga, 2016	2007 IDSA/ATS 2007 guidelines	Usual care	5	10
Notes: * Both study arms followed 2007 IDSA/ATS 2007 guidelines.

Regarding strategies for prescribing antibiotics, procalcitonin-guided therapy may reduce antibiotic usage in clinical settings that do not adhere to the 2007 Infectious Diseases Society of America/American Thoracic Society (IDSA/ATS) consensus guidelines

• The ProACT randomized controlled trial found no difference antibiotic duration when procalcitonin-guided therapy was added to the 2007 IDSA/ATS 2007 guidelines. The intervention and control groups had antibiotic durations of 4.2 and 4.3 days, respectively.
• The ProHOSP randomized controlled trial found that procalcitonin-guided therapy reduced antibiotic duration without creating harm compared to usual care. The intervention and control groups had antibiotic durations of 7.2 and 10.7 days, respectively.
• A randomized controlled trial by Uranga found that the 2007 IDSA/ATS 2007 guidelines shorted antibiotic duration without creating harm compared to usual care. The intervention and control groups had antibiotic durations of 5 and 10 days, respectively.

Choice of antibiotic therapy

• The proper antibiotic therapy is the one that provides coverage for

1. Streptococcus pneumoniae
2. Atypical bacteria (Mycoplasma, Chlamydophila, Legionella, etc.)

• Infectious diseases society of America and American thoracic society (IDSA-ATS) recommend the following guidelines for patients admitted to hospital.

1. Respiratory fluoroquinolone- Moxifloxacin 400 mg / day or levofloxacin 750 mg / day OR
2. Use a combination of second generation or third generation cephalosporin and a macrolide.
3. Macrolides, Doxycycline, fluoroquinolones are most appropriate for atypical bacteria.
4. In severe community acquired pneumonia start a cephalosporin with either a fluoroquinolone or a macrolide.
5. Hospitalized patients with community acquired pneumonia should be treated with a respiratory fluoroquinolone or a combination of cephalosporin and macrolide should be used.

• For patients treated in the outpatient department coverage for atypical organisms should be added. Young individuals usually gain herd immunity from infants and children who have been vaccinated with pneumococcal vaccination.

• Macrolides have a better outcome than fluoroquinlones which may be due to nonbactericidal effects.

• Empirical therapy with coverage for Pseudomonas aeruginosa and MRSA should be started for patients with risk factors for healthcare-associated pneumonia. The pneumonia specific criteria according to Shindo et al is

1. Hospitalization for >2 days
2. Antibiotic use during previous admission
3. Non-ambulatory status
4. Tube feedings
5. Immunocompromised status
6. Use of gastric acid suppressive agents

• Some useful interventions to decrease mortality and tranfer from floor to ICU include:

1. Aggressive fluid resuscitation
2. Prompt antibiotic initiation
3. Measure arterial blood gas in patients who have borderline hypoxemia or lactate
4. Treat co-existing illness like asthma and COPD with bronchodilators.

Timing and duration of antibiotic therapy

• High priority should be provided in the emergency room and should be immediately admitted to the intensive care unit for patients who present with 3 or more of the minor criteria:

1. Elevated blood urea nitrogen
2. Confusion
3. High respiratory rate

• First antibiotic dose should be administered within 6 hours of admission into the emergency room.

• An increased in deaths were noted when antibiotic were administered after 4 hours of administration.

• Inadvertently use of antibiotic for patients without community-acquired pneumonia who require treatment before 4 hours may increase the risk of Clostridium difficile colitis.

• Shock is an exception where antibiotic should be started within an hour of hypotension. A decrease in 8% of survival rate for each hour of delay is noted.

• Antibiotic therapy for a duration of 5-7 days has been considered as adequate for treatment of community-acquired pneumonia.

Location of treatment

• IDSA-ATS guidelines suggest that if three or more out of the nine minor criteria is present then the patient must be moved to the ICU.

• Other scores have also been developed which help to distinguish moderately ill to severely ill patients.

Antimicrobial Regimens

• 1. Empiric therapy in adults

• 1.1 Outpatient treatment

• 1.1.1 Previously healthy and no use of antimicrobials within the previous 3 months

• Preferred regimen (1): (Azithromycin 500 mg PO single dose for 1 day THEN 250 mg PO qd for 4 days) OR Azithromycin 500 mg IV single dose
• Preferred regimen (2): Clarithromycin 250 mg PO bid for 7-14 days OR Clarithromycin 1000 mg PO qd for 7 days
• Preferred regimen (3): Erythromycin 250-500 mg PO bid or tid (maximum daily dose 4 g)
• Alternative regimen: Doxycycline 100 mg PO/IV q12h

• 1.1.2 Presence of comorbidities, use of immunosuppressing drugs, or use of antimicrobials within the previous 3 months

• Preferred regimen (1): Levofloxacin 500 mg PO qd for 7-14 days OR Levofloxacin 750 mg PO qd for 5 days OR Moxifloxacin 400 mg PO/IV q24h for 7-14 days OR Gemifloxacin 320 mg PO qd for 5 or 7 days
• Preferred regimen (2): (Amoxicillin 1 g PO q8h OR Amoxicillin-clavulanate 1-2 g PO bid OR Ceftriaxone 1-2 g IV q24h OR Cefpodoxime 200 mg PO bid for 14 days OR Cefuroxime 750 mg IM/IV q8h) AND either (Azithromycin 500 mg PO single dose for 1 day THEN 250 mg PO qd for 4 days) OR (Clarithromycin 250 mg PO bid for 7-14 days OR Clarithromycin 1000 mg PO qd for 7 days) OR Erythromycin 250-500 mg PO bid or tid (maximum daily dose 4 g)
• Note: In the case of recent (past 3 months) antimicrobial therapy, an alternative from a different class should be selected.

• 1.2 Inpatient treatment

• 1.2.1 Non-ICU treatment

• Preferred regimen (1): Levofloxacin 500 mg IV qd for 7-14 days OR Levofloxacin 750 mg IV qd for 5 days OR Moxifloxacin 400 mg IV q24h for 7-14 days OR Gemifloxacin 320 mg PO qd for 5-7 days
• Preferred regimen (2): (Amoxicillin 1 g PO q8h OR Amoxicillin-clavulanate 1-2 g PO bid OR Ceftriaxone 1-2 g IV q24h OR Cefpodoxime 200 mg PO bid for 14 days OR Cefuroxime 750 mg IM/IV q8h) AND either (Azithromycin 500 mg PO single dose for 1 day THEN 250 mg PO qd for 4 days) OR (Clarithromycin 250 mg PO bid for 7-14 days OR Clarithromycin 1000 mg PO qd for 7 days) OR Erythromycin 250-500 mg PO bid or tid (maximum daily dose 4 g)

• 1.2.2 ICU treatment

• Preferred regimen (1): (Cefotaxime 1 g IM/IV q12h OR Ceftriaxone 1-2 g IV q24h OR Ampicillin-sulbactam 1.5-3 g IV q6h) AND (Levofloxacin 500 mg IV q24h for 7-14 days OR Levofloxacin 750 mg IV q24h for 5 days OR Moxifloxacin 400 mg IV q24h for 7-14 days OR Gemifloxacin 320 mg PO q24h for 5-7 days)
• Alternative regimen (1): (Cefotaxime 1 g IM/IV q12h OR Ceftriaxone 1-2 g IV q24h OR Ampicillin-sulbactam 1.5-3 g IV q6h) AND (Azithromycin 500 mg IV qd for 2 days (PO for a total of 7-10 days)
• Alternative regimen (2): Aztreonam 2 g IV q6-8h (maximum daily dose 8 g) AND (Levofloxacin 500 mg IV q24h for 7-14 days OR Levofloxacin 750 mg IV q24h for 5 days OR Moxifloxacin 400 mg IV q24h for 7-14 days OR Gemifloxacin 320 mg PO q24h for 5-7 days)

• 1.3 Special considerations

• 1.3.1 Suspected Pseudomonas

• Preferred regimen (1): Piperacillin-Tazobactam 3.375-4.5 g IV q6h for 7-14 days AND (Ciprofloxacin 400 mg IV q8h for 7-14 days OR Levofloxacin 500 mg IV qd for 7-14 days OR Levofloxacin 750 mg IV qd for 5 days)
• Preferred regimen (2): Cefepime 1-2 g IV q8-12h for 7-10 days AND (Ciprofloxacin 400 mg IV q8h for 7-14 days OR Levofloxacin 500 mg IV qd for 7-14 days OR Levofloxacin 750 mg IV qd for 5 days)
• Preferred regimen (3): (Imipenem 500 mg IV q6h for ≤5 days OR Meropenem 500 mg IV q8hr for ≤5 days) AND (Ciprofloxacin 400 mg IV q8h for 7-14 days OR Levofloxacin 500 mg IV qd for 7-14 days OR Levofloxacin 750 mg IV qd for 5 days)
• Preferred regimen (4): Piperacillin-Tazobactam 3.375-4.5 g IV q6h for 7-14 days AND (Amikacin 20 mg/kg/day IV q8-12h OR Gentamicin 3-5 mg/kg/day IV/IM q8h OR Tobramycin 3-6 mg/kg/day IV/IM q8h) AND (Azithromycin 500 mg PO single dose for 1 day THEN 250 mg PO qd for 4 days)
• Preferred regimen (5): Cefepime AND (Amikacin 20 mg/kg/day IV q8-12h OR Gentamicin 3-5 mg/kg/day IV/IM q8h OR Tobramycin 3-6 mg/kg/day IV/IM q8h) AND (Azithromycin 500 mg PO single dose for 1 day THEN 250 mg PO qd for 4 days)
• Preferred regimen (6): (Imipenem 500 mg IV q6h for ≤5 days OR Meropenem 500 mg IV q8hr for ≤5 days) AND (Amikacin 20 mg/kg/day IV q8-12h OR Gentamicin 3-5 mg/kg/day IV/IM q8h OR Tobramycin 3-6 mg/kg/day IV/IM q8h) AND (Azithromycin 500 mg PO single dose for 1 day THEN 250 mg PO qd for 4 days)
• Preferred regimen (7): (Imipenem 500 mg IV q6h for ≤5 days OR Meropenem 500 mg IV q8hr for ≤5 days) AND (Amikacin 20 mg/kg/day IV q8-12h OR Gentamicin 3-5 mg/kg/day IV/IM q8h OR Tobramycin 3-6 mg/kg/day IV/IM q8h) AND (Ciprofloxacin 400 mg IV q8h for 7-14 days OR Levofloxacin 500 mg PO qd for 7-14 days OR Levofloxacin 750 mg PO qd for 5 days)
• Preferred regimen (8): Piperacillin-Tazobactam 3.375-4.5 g IV q6h for 7-14 days AND (Ciprofloxacin 400 mg IV q8h for 7-14 days OR Levofloxacin 500 mg IV qd for 7-14 days OR Levofloxacin 750 mg IV qd for 5 days)
• Preferred regimen (9): Cefepime 1-2 g IV q8-12h for 7-10 days AND (Amikacin 20 mg/kg/day IV q8-12h OR Gentamicin 3-5 mg/kg/day IV/IM q8h OR Tobramycin 3-6 mg/kg/day IV/IM q8h) AND (Ciprofloxacin 400 mg IV q8h for 7-14 days OR Levofloxacin 500 mg IV qd for 7-14 days OR Levofloxacin 750 mg IV qd for 5 days)
• Preferred regimen (10): (Imipenem 500 mg IV q6h for ≤5 days OR Meropenem 500 mg IV q8hr for ≤5 days) AND (Ciprofloxacin 400 mg IV q8h for 7-14 days OR Levofloxacin 500 mg PO qd for 7-14 days OR Levofloxacin 750 mg PO qd for 5 days)
• Note: For penicillin-allergic patients, substitute the beta-lactam for Aztreonam 1-2 g IV q6-8h.

• 1.3.2 Suspected methicillin resistant Staphylococcus aureus (add the following)

• Preferred regimen: Vancomycin 45-60 mg/kg/day divided q8-12h OR Linezolid 600 mg PO/IV q12h for 10-14 days

• 1.3.3 Neutropenic patient

• 1.3.3.1 No risk for multi-drug resistance

• Preferred regimen: Ceftriaxone 1-2 g q24h IV or IM (max: 4 g/day) OR Levofloxacin 750 mg q24h for 7-14 days OR Moxifloxacin 400 mg PO/IV q24h for 7-14 days OR Ciprofloxacin 400 mg PO q8h for 10-14 days OR Ampicillin sulbactam 1-2 g q6-8h IV/IM (maximum: 8 g/day) OR Ertapenem 1 g IM/IV q24h for 10-14 days.

• 1.3.3.2 Risk for multi drug resistance

• Preferred Regimen: (Cefepime 1-2 g q8-12h OR Ceftazidime 2 g q8h OR Imipenem 500 mg q6h or 1g q8h OR Meropenem 1 g q8h OR Piperacillin-tazobactam 4.5 g q6h) AND (Ciprofloxacin 400 mg q8h OR Levofloxacin 750 mg q24h OR Amikacin 20 mg/kg per day OR Gentamycin 7 mg/kg per day OR Tobramycin 7 mg/kg per day) AND (Linezolid 600 mg q12h OR Vancomycin 15 mg/kg q12h).
• Note (1) : Trough levels for Gentamycin and Tobramycin should be less than 1 g/ml, and for Amikacin they should be less than 4-5 g/ml.
• Note (2) : Trough levels for Vancomycin should be 15-20 g/ml
• Note (3) : Hospital or community acquired, neutropenic patient (<500 neutrophils per mm3) Vancomycin not included in initial therapy unless high suspicion of infected intravenous access or drug-resistant Streptococcus pneumonia. Amphotericin not used unless still febrile after 3 days or high clinical likelihood.

• 2. Pathogen-directed antimicrobial therapy

• 2.1 Bacterial pathogens

• 2.1.1 Streptococcus pneumoniae

• 2.1.1.1 Penicillin sensitive (minimum inhibitory concentration < 2 mg/mL)

• Preferred regimen : Penicillin G 2-3 million units IV q4h OR Amoxicillin 875 mg PO q12h or 500 mg q8h
• Alternative regimen : Azithromycin 500 mg PO on day 1 followed by 250 mg q24h OR Cefpodoxime 200 mg PO q12h for 14 days OR Cefprozil 500 mg PO q12h for 10 days OR Cefuroxime 750 mg PO/IV q8h OR Cefdinir 300 mg PO q12h for 10 days OR Cefditoren 400 mg PO q12h for 14 day OR Ceftriaxone 1 g IV q24h, 2 g daily for patients at risk OR Cefotaxime 1 g IM/IV q12h OR Clindamycin 150-450 mg PO q6-8h (maximum: 1800 mg/day) OR Clindamycin 1.2-2.7 g/day IM/IV in 2-4 divided doses (maximum:4800 mg/day) OR Doxycycline 100 mg PI/IV q12h ORLevofloxacin 750 mg IV q24h OR Moxifloxacin 400 mg IV q24h

• 2.1.1.2 Penicillin resistant (minimum inhibitory concentration > 2 mg/mL)

• Preferred regimen (Agents chosen on the basis of susceptibililty) : Cefotaxime 1 g IM/IV q12h OR Ceftriaxone 1 g IV q24h, 2 g daily for patients at risk OR Levofloxacin 750 mg IV q24h OR Moxifloxacin 400 mg IV q24h
• Alternative regimen: Vancomycin 45-60 mg/kg/day divided q8-12h (maximum: 2000 mg/dose) for 7-21 days depending on severity OR Linezolid 600 mg PO/IV q12h for 10-14 days OR Amoxicillin 875 mg PO q12h or 500 mg q8 ( 3 g/day with penicillin ,minimum inhibitory concentration 4 ≤ microgram / mL)

• 2.1.2 Haemophilus influenzae

• 2.1.2.1 Non-beta lactamase producing

• Preferred regimen: Amoxicillin 875 mg PO q12h or 500 mg q8h
• Alternative regimen : Levofloxacin 750 mg IV q24h OR Moxifloxacin 400 mg IV q24h OR Doxycycline 100 mg PO/IV q12h OR Azithromycin 500 mg PO on day 1 followed by 250 mg q24h on days 2-5 OR Clarithromycin 250 mg q12h for 7-14 days or 1000 mg q24h for 7 days

• 2.1.2.2 Beta lactamase producing

• Preferred regimen: 2nd or 3rd Generation Cephalosporin OR Amoxicillin-clavulanate 2 g q12h
• Alternative regimen: Levofloxacin 750 mg IV q24h OR Moxifloxacin 400 mg IV q24h OR Doxycycline 100 mg PO/IV q12h OR Azithromycin 500 mg PO on day 1 followed by 250 mg q24h on days 2-5 OR Clarithromycin 250 mg q12h for 7-14 days or 1000 mg q24h for 7 days

• 2.1.2 Bacillus anthracis (inhalational)

• Preferred Regimen :Ciprofloxacin 500-750 mg q12h for 7-14 days OR Levofloxacin 500 mg q24h for 7-14 days or 750 mg q24h for 5 days OR Doxycycline 100 mg PO/IV q12h
• Alternate Regimen : Other Fluoroquinolones OR B-lactam (if susceptible) OR Rifampin 600 mg PO/IV q24h for 4 days OR Clindamycin 150-450 mg PO q6-8h OR Chloramphenicol 50-100 mg/kg/day IV in divided q6h

• 2.1.3 Enterobacteriaceae

• Preferred Regimen: 3rd generation cephalosporin OR Carbapenem- (Imipenem-Cilastatin, OR Meropenem, OR Ertapenem) (drug of choice if extended-spectrum b-lactamase producer)
• Alternate Regimen : b-Lactam / b-lactamase inhibitor- (Piperacillin-Tazobactam for gram-negative bacilli, OR Ticarcillin-Clavulanate OR Ampicillin-Sulbactam OR Amoxicillin-Clavulanate) OR (Levofloxacin 750 mg IV q24h OR Moxifloxacin 400 mg IV q24h)

• 2.1.4 Pseudomonas aeruginosa

• Preferred Regimen: (Ticarcillin 200-300 mg/kg/day in divided doses q4-6h (maximum: 18 g/day) OR Piperacillin 6-8 g/day IM/IV (100-125 mg/kg daily) divided q6-12h OR Ceftazidime 500 mg to 1 g q8h OR Cefepime 1-2 g q12h for 10 days OR Aztreonam 2 g IV q6-8h (maximum: 8 g/day) OR Imipenem 500 mg IV q6h OR Meropenem 500 mg IV q8h) AND (Ciprofloxacin 500-750 mg q12h for 7-14 days OR Levofloxacin 750 mg daily OR Aminoglycoside)
• Alternative Regimen: Aminoglycoside AND (Ciprofloxacin 500-750 mg q12h for 7-14 days OR Levofloxacin 750 mg daily)

• 2.1.5 Staphylococcus aureus

• 2.1.5.1 Methicillin sensitive

• Preferred Regimen : Nafcillin 1000-2000 mg q4h OR Oxacillin 2 g IV q4h OR Flucloxacillin 250 mg IM/IV q6h
• Alternative Regimen : Cefazolin 500 mg IV q12h OR Clindamycin 150-450 mg PO q6-8h

• 2.1.5.2 Methicillin resistant

• Preferred Regimen : Vancomycin 45-60 mg/kg/day divided q8-12h (max: 2000 mg/dose) for 7-21 days OR Linezolid 600 mg PO/IV q12h for 10-14 days
• Alternative Regimen: Trimethoprim-Sulfamethoxazole 1-2 double-strength tablets (800/160 mg) q12-24h

• 2.1.6 Klebsiella pneumonia

• 2.1.6.1 Resistant to third generation cephalosporins and aztreonam

• Preferred regimen (1): Imipenem 0.5 g IV q6h OR Meropenem 0.5–1 g IV q8h

• 2.1.6.2 Klebsiella pneumoniae Carbapenemase producers

• Preferred regimen (1): Colistin (=Polymyxin E).In USA : Colymycin-M 2.5-5 mg/kg per day of base divided into 2-4 doses 6.7-13.3 mg/kg per day of colistimethate sodium (max 800 mg/day). Elsewhere: Colomycin and Promixin ≤60 kg, 50,000-75,000 IU/kg per day IV in 3 divided doses (=4-6 mg/kg per day of colistimethate sodium). >60 kg, 1-2 mill IU IV tid (= 80-160 mg IV tid) OR Polymyxin B (Poly-Rx) 15,000–25,000 units/kg/day divided q12h
• Note (1): some strains which hyperproduce extended spectrum beta-lactamase are primarily resistant to Ticarcillin-Clavulanate, Piperacillin-Tazobactam
• Note (2): Extended spectrum beta-lactamases inactivates all Cephalosporins, beta-lactam/beta-lactamase inhibitor drug activation not predictable; co-resistance to all Fluoroquinolones & often Aminoglycosides.
• Note (3): Can give IM, but need to combine with “caine” anesthetic due to pain.

• 2.1.7 Moraxella catarrhalis

• Preferred regimen: Amoxicillin-Clavulanate (Augmentin) 2 tablets po bid ( (or)500/125 mg 1 tablet po tid (or) 875/125 mg 1 tablet po bid) OR Cephalosporins- Cefdinir 300 mg po q12h (or) 600 mg q24h, OR (Cefditoren pivoxil 200–400 mg, 2 tabs po bid,OR Cefpodoxime proxetil 0.1–0.2 g po q12h, OR Cefprozil 500 mg po q12h), OR Cefoxitin 1 g q8h–2 g IV/IM q4h, OR (Cefuroxime 0.75–1.5 g IV/IM q8h,ORCefotaxime 1 g q8–12h to 2 g IV q4h, OR Ceftazidime 1–2 g IV/IM q8–12h) OR Trimethoprim-Sulfamethoxazole Single-strength (SS) is Trimethoprim 80 mg / Sulfamethoxazole 400 mg ,OR (double-strength (DS) Trimethoprim 160 mg /Sulfamethoxazole 800 mg)
• Alternative regimen: Azithromycin 500 mg IV q24h ,OR Clarithromycin 0.5 g po q12h, OR Telithromycin 800 mg po q24h (two 400 mg tabs po q24h).

• 2.1.8 Stenotrophomonas maltophilia

• Preferred regimen: Trimethoprim-Sulfamethoxazole Single-strength (SS) tablet is Trimethoprim 80 mg / Sulfamethoxazole 400 mg, double-strength (DS) tablet is Trimethoprim 160 mg / Sulfamethoxazole 800 mg OR IV treatment (base on TMP component): standard 8–10 mg per kg per day divided q6h, q8h, or q12h.
• Alternative regimen: Ticarcillin-Clavulanate 3.1 g IV q4–6h (Ticarcillin 3 g, Clavulanate 0.1 g per vial) AND Aztreonam 1 g IV q6h (or) 2 g IV q8h
• Note (1): Potential synergy with Trimethoprim-Sulfamethoxazole AND Ticarcillin-Clavulanate.
• Note (2): Stenotrophomonas is one of the microorganisms causing hospital-acquired pneumonia usually with mechanical ventilation.

• 2.1.9 Bordetella pertussis

• Preferred Regimen:Azithromycin 500 mg PO on day 1 followed by 250 mg q24h
• Alternative Regimen: Trimethoprim-Sulfamethoxazole 1-2 double-strength tablets (800/160 mg) q12-24h

• 2.1.10 Anaerobes (aspiration pneumonia)

• Preferred Regimen: Piperacillin-Tazobactam 3.375 g IV q6h for 7-10 days (For gram-negative bacilli) OR Ticarcillin Clavulanate 200-300 mg/kg/day IV divided q4-6h (max: 18 g/day) OR Ampicillin-Sulbactam 1500-3000 mg IV q6h OR Amoxicillin-Clavulanate 250-500 mg PO q8h or 875 mg q12h OR Clindamycin 150-450 mg PO q6-8h (max: 1800 mg/day)
• Alternative Regimen: Carbapenem -(Imipenem-Cilastatin, OR Meropenem, OR Ertapenem)

• 2.1.11 Mycobacterium tuberculosis

• 2.1.11.1 Intensive phase

• Preferred Regimen: Isoniazid 5 mg/kg/day q24h daily for 2 months (usual dose: 300 mg/day) AND Rifampin 10 mg/kg/day daily for 2 months (maximum: 600 mg / day) AND Ethambutol 5-25 mg/kg daily for 2 months (maximum dose: 1.6 g) AND Pyrazinamide 1000 - 2000 mg / day daily for 2 months.
• Alternative regimen (1): Isoniazid 5 mg/kg/day q24h daily for 2 months (usual dose: 300 mg/day) AND Rifampin 10 mg/kg/day daily for 2 months (maximum: 600 mg / day) AND Ethambutol 5-25 mg/kg daily for 2 months (maximum dose: 1.6 g) AND Pyrazinamide 1000 - 2000 mg / day daily for 2 months.
• Alternative regimen (2): Isoniazid 5 mg/kg/day q24h 3 times per week for 2 months (usual dose: 300 mg/day) AND Rifampin 10 mg/kg/day 3 times per week for 2 months (maximum: 600 mg / day) s AND Ethambutol 5-25 mg/kg (maximum dose: 1.6 g) 3 times per week for 2 months AND Pyrazinamide 1000 - 2000 mg / day 3 times per week for 2 months.

• 2.1.11.2 Continuation phase

• Preferred Regimen:Isoniazid 300 mg/day PO daily for 4 months (5 mg/kg/day) AND Rifampicin 600 mg/day PO daily for 4 months (10 mg/kg/day)
• Alternative regimen (1): Isoniazid 300 mg/day PO 3 times per week for 4 months (5 mg/kg/day) AND Rifampicin 600 mg/day PO 3 times per week for 4 months (10 mg/kg/day)

• 2.1.12 Yersinisa pestis

• Preferred Regimen: Streptomycin 15 mg/kg/day (max 1 g/day) OR Gentamicin 7 mg/kg/day
• Alternate Regimen: Doxycycline 100 mg PO/IV q12h OR Levofloxacin 750 mg IV q24h OR Moxifloxacin 400 mg IV q24h

• 2.1.13 Atypical bacteria

• 2.1.13.1 Mycoplasma pneumoniae

• Preferred Regimen:Azithromycin 500 mg PO on day 1 followed by 250 mg q24h OR Tetracycline Oral: 250-500 mg q6h
• Alternate Regimen: Levofloxacin 750 mg IV q24h OR Moxifloxacin 400 mg IV q24h

• 2.1.13.2 Chlamydophila pneumoniae

• Preferred Regimen: Azithromycin 500 mg PO on day 1 followed by 250 mg q24h OR Tetracycline 250-500 mg PO q6h
• Alternate Regimen: Levofloxacin 750 mg IV q24h OR Moxifloxacin 400 mg IV q24h

• 2.1.13.3 Legionella spp.

• Preferred Regimen: Levofloxacin 750 mg IV q24h OR Moxifloxacin 400 mg IV q24h OR Azithromycin 500 mg PO on day 1 followed by 250 mg q24h
• Alternate Regimen: Doxycycline 100 mg PO/IV q12h

• 2.1.13.4 Chlamydophila psittaci

• Preferred Regimen: Tetracycline 250-500 mg PO q6h
• Alternate Regimen: Azithromycin 500 mg PO on day 1 followed by 250 mg q24h

• 2.1.13.5 Coxiella burnetii

• Preferred Regimen: Tetracycline 250-500 mg PO q6h
• Alternate Regimen: Azithromycin 500 mg PO on day 1 followed by 250 mg q24h

• 2.1.13.6 Francisella tularensis

• Preferred Regimen: Doxycycline 100 mg PO/IV q12h
• Alternate Regimen: Gentamicin 7 mg/kg/day OR Streptomycin 15 mg/kg/day (maximum: 1 g)

• 2.1.13.7 Burkholderia pseudomallei

• Preferred Regimen : Carbapenem -(Imipenem-Cilastatin, OR Meropenem, OR Ertapenem) OR Ceftazidime 0.5-1 g q8h
• Alternate Regimen: Levofloxacin 750 mg IV q24h OR Moxifloxacin 400 mg IV q24h OR Trimethoprim-Sulfamethoxazole 1-2 double-strength tablets (800/160 mg) q12-24h

• 2.1.13.8 Acinetobacter species

• Preferred Regimen : Carbapenem-(Imipenem-Cilastatin, OR Meropenem, OR Ertapenem)
• Alternate Regimen: Cephalosporin-Aminoglycoside OR Ampicillin-Sulbactam OR Colistin 2.5-5 mg/kg/day IM/IV divided q6-12h (maximum: 5 mg/kg/day)

• 2.1.14 Gram-positive filamentous bacteria

• 2.1.14.1 Actinomyces spp.

• Preferred regimen: Penicillin V 1 g po qid 2-6 wk
• Alternative regimen: Tetracycline 500 mg po q 6 h OR Doxycycline 100 mg q 12 h
• Note: Minocycline, Clindamycin, and Erythromycin have also been successful.

• 2.1.14.2 Nocardia spp., ,

• 2.1.14.2.1 Initial intravenous therapy (induction therapy)

• Preferred regimen: Trimethoprim-Sulfamethoxazole (15 mg/kg/day IV of the trimethoprim component in 2 to 4 divided doses) for at least three to six weeks AND Amikacin (7.5 mg/kg IV q12h) for at least three to six weeks
• Alternative regimen: Imipenem (500 mg IV q6h) AND Amikacin (7.5 mg/kg IV q12h)
• Note (1): If the patient is allergic to Sulfonamides, desensitization should be performed when possible.
• Note (2): If the isolate is susceptible to the third-generation cephalosporins (Ceftriaxone, Cefotaxime), Imipenem can be switched to one of these agents.
• Note (3): Selected patients who clinically improve with induction intravenous therapy and do not have CNS disease may be switched to oral monotherapy (usually after three to six weeks) based upon susceptibility results.

• 2.1.14.2.2 Oral maintenence therapy

• Preferred regimen: A sulfonamide (eg,Trimethoprim-Sulfamethoxazole 10 mg/kg/day of the trimethoprim component in 2 or 3 divided doses) AND / OR Minocycline (100 mg bd) AND / OR Amoxicillin-Clavulanate (875 mg bd)
• Note (1): Selected patients who clinically improve with induction intravenous therapy and do not have CNS disease may be switched to oral monotherapy (usually after three to six weeks) based upon susceptibility results.
• Note (2): The duration of intravenous therapy varies with the patient's immune status. In immunocompromised patients, maximal tolerated doses should be given intravenously for at least six weeks and until clinical improvement has occurred; in contrast, immunocompetent patients may be successfully treated with a shorter duration of intravenous therapy. Following the intravenous induction phase, patients may be stepped down to oral antibiotics based upon susceptibility studies
• Note (3): Serious pulmonary infection is treated for 6 to 12 months or longer.

• 2.2 Viral pathogens

• 2.2.1 Influenza virus

• Preferred Regimen: Oseltamivir 75 mg PO q12h for 5 days (initiated within 48 hours of onset of symptoms) OR Zanamivir Two inhalations (10 mg total) q12h for 5 days (Doses on first day should be separated by at least 2 hours; on subsequent days, doses should be spaced by ~12 hours)

• 2.2.2 Cytomegalovirus

• Preferred regimen (1): Ganciclovir Induction therapy 5 mg/ kg IV every 12 h for normal GFR; maintenance therapy 5 mg/kg IV daily; 1 g orally every 8 h with food.
• Preferred regimen (2): Valganciclovir Induction therapy 900 mg orally every 12 h; maintenance therapy 900 mg daily.
• Alternative regimen (1): Foscarnet Induction therapy 60 mg/ kg every 8 h for 14–21 days or 90 mg/kg every 12 h for 14–21 days; maintenance therapy 90–120 mg/kg per day as a single infusion.
• Alternative regimen (2): Cidofovir Induction therapy 5 mg/ kg per week for 2 weeks, followed by maintenance therapy every 2 weeks.

• 2.3 Fungal pathogens

• 2.3.1 Coccidioides species

• Preferred Regimen: Itraconazole 200 mg q12h OR Fluconazole 200-400 mg daily for 3-6 month
• Alternative Regimen: Amphotericin B 0.5-0.7 mg/kg/day
• Note: No therapy is indicated for uncomplicated infection, treat only if complicated infection

• 2.3.2 Histoplasmosis

• Preferred Regimen: Itraconazole 200 mg q12h
• Alternative Regimen: Amphotericin B 0.5-0.7 mg/kg/day

• 2.3.3 Blastomycosis

• Preferred Regimen: Itraconazole 200 mg q12h
• Alternate Regimen: Amphotericin B 0.5-0.7 mg/kg/day

Corticosteroids

Clinical practice guidelines from 2017 recommend restricting steroids to patients with refractory septic shock.

Steriods have been studied in various populations of patients with community-acquired pneumonia CAP):

• Ambulatory outpatients with CAP
• Inpatients with CAP.
  • Benefit of steroids: one study found a relative risk ratio of prednisone 50 mg daily for 7 days, as compared to placebo, reduced the time to median time to clinical stability from 4.4 to to 1.3 days. In another randomized controlled trial of adults with community-acquired pneumonia, dexamethasone can reduce length of hospital stay.
  • Harm from steroids: ne trial found harm due to increased GI bleeding. An older randomized controlled trial found harm from late-failures..
• Inpatients with severe CAP.
  • Benefit of steroids:

Management of Pneumonia with Parapneumonic Effusion

Shown below is an algorithm for the management of parapneumonic effusion in pediatric patients based on the 2011 Clinical Practice Guidelines by the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America.
Abbreviations:

Confirm pleural effusion with chest X-ray. If not conclusive, order chest ultrasound or CT

Determine the size of the effusion

Small < 25% opacification of the thorax

Moderate Between 25-50% opacification of the thorax

Large > 50% opacification of the thorax

Give antibiotic treatment. Pleural drainage is not recommended. Is the patient improving?

Does the patient has respiratory distress?

Order a ultrasound or CT to assess effusion size and loculation Pleural drainage is indicated to drain fluid and send sample for culture Is the pleural effusion loculated?

Yes

No

Yes

No

Yes "Complicated"

No "Simple"

Continue antibiotic therapy

Reassess the size of the effusion and follow the algorithm according to the size of effusion.

Follow algorithm for large effusion

Administer IV antibiotics Obtain chest ultrasound Do thoracocentesis to obtain a fluid sample for culture

Chest tube drain with fibrinolytics If there is no improvement, do a video-assisted thoracoscopic surgery

3 options for drainage: Chest tube Chest tube + fibrinolytics Video-assisted thoracoscopic surgery

Management of Non-responding Pneumonia

Definition

A failure to response even after 7 days of antibiotic treatment is categorized into non responding pneumonia. A progressive or deterioration causing respiratory faiure as septic shock within 72 hrs of hospital admission.

Management

The following steps should be taken as soon as the patient doesn't respond to treatment

1. Transfer to a higher centre
2. Order further diagnostic tests
3. Change treatment

After a failure of treatment the following causes should be considered before proceeding further.

• Resistant microorganism
• Uncovered pathogen
• Nosocomial superinfection/Pneumonia
• Complication of pneumonia (e.g., BOOP)
• Misdiagnosis:

1. Pulmonary Embolism
2. CHF
3. Vasculitis

• Inaccurate diagnosis

The following actions are performed to find out the cause of a non responding pneumonia.

Cultures

A repeat blood culture should be performed if the pneumonia deteriorates .Inspite of treatment with prior antibiotic therapy blood cultures might still show high colonies.

Rapid urinary antigens

S. pneumoniae and L. pneumophila may remain positive inspite of starting antibiotic therapy.

Stopping B-Lactam

Stopping B-Lactam component of the combination may be important to rule out drug fever.

Pneumococcal Antigen test

Some host may be have poor immunity and hence a pneumococcal antigen test should be scheduled to rule out that the cause was not incorrect antibiotics.

Obtain cultures from catheters

Extrapulmonary infection in ICU patients should be ruled out by obtaining cultures from intravascular catheter. A culture must also be obtained to rule out urinary, abdominal and skin infections which may be the result of the non response to treatment.

Infectious Diseases Society of America/American Thoracic Society Consensus Recommendation on Empiric Antibiotic Treatment of Community-acquired Pneumonia in Adults

“

Previously Healthy and No Risk Factors for Drug Resistant Streptococcus Pneumoniae A macrolide (azithromycin, clarithromycin, or erythromycin (Strong recommendation; level I evidence) Doxycycline (Weak recommendation; level III evidence) Presence of Comorbidities or Other Risks for Drug Resistant Streptococcus Pneumoniae 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: A respiratory fluoroquinolone (moxifloxacin, gemifloxacin, or levofloxacin [750 mg]) (Strong recommendation; level I evidence) A beta-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.) In Regions With a High Rate (>25%) of Infection In regions with a high rate (>25%) of infection with high-level (minimal inhibitory concentration [MIC], >16 micrograms/mL) macrolide-resistant S. pneumoniae, consider the use of alternative agents for any patient, including those without comorbidities. (Moderate recommendation; level III evidence) Inpatient, Non-ICU Treatment The following regimens are recommended for hospital ward treatment. A respiratory fluoroquinolone (Strong recommendation; level I evidence) A beta-lactam plus a macrolide (Strong recommendation; level I evidence) (Preferred beta-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.) Inpatient, ICU Treatment The following regimen is the minimal recommended treatment for patients admitted to the ICU. A beta-lactam (cefotaxime, ceftriaxone, or ampicillin-sulbactam) plus either azithromycin (level II evidence) or a fluoroquinolone (Strong recommendation; level I evidence) (For penicillin-allergic patients, a respiratory fluoroquinolone and aztreonam are recommended.) For Pseudomonas infection, use an antipneumococcal, antipseudomonal beta-lactam (piperacillin-tazobactam, cefepime, imipenem, or meropenem) plus either ciprofloxacin or levofloxacin (750-mg dose) or the above beta-lactam plus an aminoglycoside and azithromycin or the above beta-lactam plus an aminoglycoside and an antipneumococcal fluoroquinolone (for penicillin-allergic patients, substitute aztreonam for the above beta-lactam). (Moderate recommendation; level III evidence) For community-acquired methicillin resistant Staphylococcus aureus (CA-MRSA) infection, add vancomycin or linezolid. (Moderate recommendation; level III evidence)

”

For Level of evidence classification click here.

Infectious Diseases Society of America/American Thoracic Society Consensus Recommendation on Pandemic Influenza Community-acquired pneumonia in Adults

“

Pathogen Directed Therapy Once the etiology of CAP has been identified on the basis of reliable microbiological methods, antimicrobial therapy should be directed at that pathogen (Moderate recommendation; level III evidence) Early treatment (within 48 h of the onset of symptoms) with oseltamivir or zanamivir is recommended for influenza A. (Strong recommendation; level I evidence) Use of oseltamivir and zanamivir is not recommended for patients with uncomplicated influenza with symptoms for >48 h (level I evidence), but these drugs may be used to reduce viral shedding in hospitalized patients or for influenza pneumonia. (Moderate recommendation; level III evidence) Pandemic Influenza Patients with an illness compatible with influenza and with known exposure to poultry in areas with previous H5N1 infection should be tested for H5N1 infection. (Moderate recommendation; level III evidence) In patients with suspected H5N1 infection, droplet precautions and careful routine infection control measures should be used until an H5N1 infection is ruled out. (Moderate recommendation; level III evidence) Patients with suspected H5N1 infection should be treated with oseltamivir (level II evidence) and antibacterial agents targeting S. pneumoniae and S. aureus, the most common causes of secondary bacterial pneumonia in patients with influenza. (Moderate recommendation; level III evidence)

”

For Level of evidence classification click here.

Infectious Diseases Society of America/American Thoracic Society Consensus Recommendation on Time, Route, and Duration of Community-acquired pneumonia in Adults (DO NOT EDIT)

“

Time to First Antibiotic Dose For patients admitted through the emergency department (ED), the first antibiotic dose should be administered while still in the ED. (Moderate recommendation; level III evidence) Switch from Intravenous to Oral Therapy Patients should be switched from intravenous to oral therapy when they are hemodynamically stable and improving clinically, are able to ingest medications, and have a normally functioning gastrointestinal tract. (Strong recommendation; level II evidence). Patients should be discharged as soon as they are clinically stable, have no other active medical problems, and have a safe environment for continued care. Inpatient observation while receiving oral therapy is not necessary. (Moderate recommendation; level II evidence) Duration of Antibiotic Therapy Patients with CAP should be treated for a minimum of 5 days (level I evidence), should be afebrile for 48 to 72 h, and should have no more than 1 CAP-associated sign of clinical instability before discontinuation of therapy. (level II evidence) (Moderate recommendation) A longer duration of therapy may be needed if initial therapy was not active against the identified pathogen or if it was complicated by extrapulmonary infection, such as meningitis or endocarditis. (Weak recommendation; level III evidence)

”

For Level of evidence and classes click here.

Infectious Diseases Society of America/American Thoracic Society Consensus Recommendation on Other Treatments Considerations for Acquired Pneumonia in Adults (DO NOT EDIT)

“

This recommendation has been removed due to the market withdrawal of drotrecogin alfa. Hypotensive, fluid-resuscitated patients with severe CAP should be screened for occult adrenal insufficiency. (Moderate recommendation; level II evidence) Patients with hypoxemia or respiratory distress should receive a cautious trial of noninvasive ventilation (NIV) unless they require immediate intubation because of severe hypoxemia (arterial oxygen pressure/fraction of inspired oxygen [PaO2/FiO2] ratio <150) and bilateral alveolar infiltrates. (Moderate recommendation; level I evidence) Low-tidal-volume ventilation (6 cm3/kg of ideal body weight) should be used for patients undergoing ventilation who have diffuse bilateral pneumonia or acute respiratory distress syndrome. (Strong recommendation; level I evidence)

”

For Level of evidence and classes click here.

Infectious Diseases Society of America/American Thoracic Society Consensus Recommendation on Non Responding Acquired Pneumonia in Adults (DO NOT EDIT)

“

Because of the limitations of diagnostic testing, the majority of CAP is still treated empirically. Critical to empirical therapy is an understanding of the management of patients who do not follow the normal response pattern.

”

For Level of evidence and classes click here.