4.08 - Respiratory Tract Infections

A) Adults

Disease / Etiology

Preferred

Alternative

Comments

Community Acquired Pneumonia

S. pneumoniae, Klebsiella pneumonia, H. influenzae, Moraxella catarrhalis, Legionella sp., Mycoplasma pneumoniae, Chlamydophila (pneumoniae & psittaci), respiratory viruses.

Staph aureus can also cause CAP, but is uncommon.


Low Severity:
CURB 65 = 0 – 1
or
CRB 65 score = 0

 
*No risk of Drug Resistant Streptococcus Pneumoniae (DRSP)
Amoxycillin 1 g PO q8H
+
Doxycycline 200 mg PO stat, then 100mg PO q12H

*With risk of DRSP
Co-amoxiclav 625 mg PO q12H
+
Doxycycline 200 mg PO stat then 100 mg PO q12H

 
Azithromycin 500 mg PO q24H

for 3 days

Hospitalisation usually is not required.

Penicillin allergy: 
Refer to Respiratory team to start
Moxifloxacin 400 mg PO q24H

Moderate severity:
CURB 65 = 2, ( 9% mortality
or

CRB 65 = 1 - 2


Co-amoxiclav 1.2 gm IV q8H
+
Azithromycin 500 mg IV q24H

Ceftriaxone 2 gm IV q24H
+
Azithromycin 500 mg IV q24H

Hospitalisation is recommended.

High Severity:
CURB 65 = 3–5, 15–40% mortality)
or
CRB = 3 - 4

 
Piperacillin / Tazobactam 4.5 gm IV q8H
+
Azithromycin 500 mg IV q24H


Cefepime 2 gm IV q12
H
+
Azithromycin 500 mg IV q24
H

Patients should be managed in HDU or ICU.

For those with septicaemia, consider aminoglycoside.

Healthcare Associated Pneumonia

Algorithm for assessment of healthcare-associated pneumonia (HCAP) is dependent on the disease severity and presence of multidrug resistant (MDR) risks.

MDR Risk Factors:

  1. Recent (within last 90 days) antibiotic therapy
  2. Recent (within last 90 days) hospitalisation
  3. Presence of immunosuppression or on immune suppressant
  4. Presence of poor functional status
 
Group 1
Not severe
0 - 1 risk

Co-amoxiclav 625 mg PO q12H
+
Doxycycline 200 mg PO stat then 100 mg PO q12H

   
Penicillin allergy:
Refer to Respiratory team to start
Moxifloxacin 400 mg PO q24H.
 
Group 2
Not severe
≥ 2 risks
and
Group 3
Severe 0 - 1 risk

 
Piperacillin / Tazobactam 4.5 gm IV q8H
+
Azithromycin 500 mg IV q24H
 
Cefepime 2 gm IV q8H + Azithromycin 500 mg IV q24H
 

Group 4
Severe ≥ 2 risks

 
Piperacillin / Tazobactam
4.5 gm IV q8H
±
Gentamicin 3 - 5 mg/kg IV q24H OR Amikacin 15 mg/kg IV q24H
+
Azithromycin 500 mg IV q24H

 
Cefepime 2 gm IV q8H
±
Gentamicin 3 - 5 mg/kg IV q24H OR Amikacin 15 mg/kg IV q24H
+
Azithromycin 500 mg IV q24H
 
If CrCl < 50 mL/min, substitute Aminoglycoside with Ciprofloxacin.

Monitor Aminoglycoside therapeutic level on the 3rd dose of Aminoglycoside.

Hospital Acquired Pneumonia

Pseudomonas aeruginosa, Acinetobacter baumannii, various gram negative organisms and MRSA.

Many of these are multi-drug-resistant organisms.

Atypical organisms, e.g. Mycoplasma sp, Chlamydophila sp or Legionella are rare. 

Most pneumonia can be treated for 7 - 8 days. MROs (acinetobacter, pseudomonas), Staph aureus & Legionella usually require 10 - 14 days of treatment.


Mild to Moderate
< 5 days in hospital
0 - 1 MDR Risk

Co-amoxiclav 1.2 gm IV q8H
+
Azithromycin 500 mg PO q24H


Ceftriaxone 2 gm IV q24H
+
Azithromycin 500 mg PO q24H

Penicillin allergy:
Refer to Respiratory team to start
Moxifloxacin 400 mg PO q24H.

Severe
 
Piperacillin / Tazobactam 4.5 gm IV q8H
±
Gentamicin 3 - 5 mg/kg IV q24H OR Amikacin 15 mg/kg IV q24H

Imipenem 500 mg IV q6H
 
If patient suspected to be colonized with MRSA, add vancomycin 20 mg/kg IV single dose then 15 mg/kg IV q12H.

If patient is colonized with extreme drug resistant Acinetobacter baumaunii, start Colistin 3 MU IV q8H.

If CrCl < 50 mL/min, substitute Aminoglycoside with Ciprofloxacin.

Aspiration Pneumonia

Most aspiration is sterile & requires physiotherapy, not antibiotics.

If infection develops, anaerobes & mouth streptococci (e.g. Milleri/anginosus) should be treated.

 
Community Acquired
 
Co-amoxiclav 625 mg PO q12H OR Co-amoxiclav 1.2 gm IV q8H
 
Ceftriaxone 2 gm IV q24H
Minor degree of aspiration does not require antibiotics.

With acute intestinal obstruction:
Add Metronidazole 500 mg IV q8H.

 
Hospital Acquired
 
Piperacillin / Tazobactam 4.5 gm IV q8H

   

Other Lower Respiratory Tract Infections

Lung Abscess

  • Those with cavities < 2 cm is also known as necrotising pneumonia or lung gangrene.
  • It is often secondary to aspiration - hence, anaerobes are important. 
  • Other causes include Gram positive cocci, Klebsiella pneumonia, S. milleri / anginosus and rarely, Norcardia sp..

In the dependent part of the lung (posterior segment & lower lobe)


Community acquired:
Co-amoxiclav 1.2 gm IV q8H

 
Ceftriaxone 2 gm IV q24H

Duration: 3 - 6 weeks.

Initially IV, then could be switched to oral treatment after 1-2 weeks if defervescence & clinical improvement observed.

Hospital acquired:
Piperacillin / Tazobactam 4.5 gm IV q8H

 
Cefepime 2 gm IV q8H

Multiple cavities and critically ill:
Staph aureus 
Klebsiella pneumoniae
Burkholderia pseudomallei (Melioidosis)

 
Cloxacillin 2 gm IV q6H
+
Ceftazidime 2 gm IV q6H
   

Acute Exacerbation of Bronchiectasis

Pseudomonas aeruginosa, Haemophilus influenza, Streptococcus pneumoniae, Moraxella, Catarrhalis, Staph aureus.

 
Mild

 
Co-amoxiclav 625 mg PO q8H

 
Moxifloxacin 400 mg PO q24H
OR Cefuroxime 500 mg PO q12H

 
 
Moderate

 
Co-amoxiclav 1.2 gm IV q8H

 
Ceftriaxone 2 gm IV q24H
 
 
Severe
or
Failed Oral Therapy


 
Ceftazidime 2 gm IV q8H
±
Gentamicin 3 - 5 mg/kg IV q24H OR Amikacin 15 mg/kg IV q24H
(if resistant organism is suspected)

 
Ciprofloxacin 400 mg IV q12H OR Cefepime 2 gm IV q8H
 

Bronchiectasis (chronic suppressive treatment)

Antibiotic treatment may only be justified for patients with frequent exacerbations (≥ 3 per last 12 months; or ≥ 2 per last 12 months with significant comorbidities), antibiotic treatment may be justified


Regular maintenance treatment


Azithromycin 500 mg PO
3 times/week

 
Erythromycin Ethyl Succinate (EES) 400 mg PO q12H

 

 Cyclical antibiotic


Ceftazidime 2 gm IV q8H
± Gentamicin 3 - 5 mg/kg IV q24H OR Amikacin 15 mg/kg IV q24H

 
Cefepime 2 gm IV q8H OR Ciprofloxacin 750 mg PO q12H 
 
Duration: every 12 weeks.

Bronchiectasis Eradication Treatment


Pseudomonas with NO MDR risk

 
Ciprofloxacin 750 mg PO q12H

   
 
Pseudomonas with MDR risk


Antibiotics (subject to sensitivity result) for 2 weeks

   
Consider nebulised colistin.

Acute Exacerbation of COPD 

 
Mild

 
Amoxycillin 1 gm PO q8H
 
Azithromycin 500 mg PO q24H


Not all COPD exacerbations require antibiotic therapy.

Antibiotic may be considered if the patient has one or more of the following symptoms or scenario:
· purulent sputum production
· fever
· exacerbation which requires hospitalisation
 
Moderate

 
Co-amoxiclav 625 mg PO q8H


Moxifloxacin 400 mg PO q24H
 
Severe
(0 - 1 MDR risk*) and (No recent hospitalization)

 
Co-amoxiclav 1.2 gm IV q8H
 
Ceftriaxone 2 gm IV q24H
 
Severe
(≥ 2 MDR risks*) or (Recent hospitalisation)

 
Piperacillin / Tazobactam 4.5 gm IV q8H
 
Cefepime 2 gm IV q8H


B) Paediatrics

Disease / Etiology

Preferred

Alternative

Comments

Community Acquired Bacterial Pneumonia, Pleural Effusion and Empyema

 
1 - 3 months
Staphylococcus aureus
Streptococcal pneumoniae
Haemophilus influenza


 

Cloxacillin 50 mg/kg IV q6H
+
Ampicillin 50 mg/kg IV q6H
 

Co-amoxiclav 25 mg/kg (Amoxicillin component) IV q8H
OR
Cefuroxime 25 - 50 mg/kg IV q6-8H
 

Use Cloxacillin if one suspects Staphylococcus aureus (MSSA) pneumoniae / sepsis in critically ill infants, children < 1 year of age or in the presence of pneumatocoeles.

For patients with significant beta-lactam allergy, macrolides are alternatives.

Add IV Metronidazole or change Amoxicillin to Co-amoxiclav if aspiration of anaerobes is a possibility.
 
Chlamydia trachomatis
Bordetella pertussis

 
Erythromycin 15 mg/kg PO q6H OR Azithromycin 15 mg/kg PO on Day 1 then 7.5 mg/kg PO Day 2 - 5; OR 15 mg/kg PO q24H for 3 days


3 months to 5 years
Streptococcal pneumoniae
Staphylococcus aureus
Haemophilus influenza


 

Ampicillin 50 mg/kg IV q6H
 

Co-amoxiclav 25 mg/kg (Amoxicillin component) IV q8H
OR
Cefuroxime 25 - 50 mg/kg IV q6 - 8H
 

Chlamydia pneumoniae
Mycoplasma pneumoniae

 
Erythromycin 15 mg/kg PO q6H OR Azithromycin 15 mg/kg PO on Day 1, then 7.5 mg/kg PO Day 2 - 5; OR 15 mg/kg PO q24H for 3 days

 
More than 5 years
Streptococcal pneumoniae
Mycoplasma pneumoniae
Moraxella cattarhalis
Staphylococcus aureus
Haemophilus influenza
 

 

Ampicillin 50 mg/kg IV q6H
OR
Benzylpenicillin 50,000 - 100,000 units/kg IV q6H
(Macrolide for Mycoplasma)
 

Co-amoxiclav 25 mg/kg (Amoxicillin component) IV q8H
OR
Cefuroxime 25 - 50 mg/kg IV q6 - 8H
 

Chlamydia pneumoniae

 
Erythromycin 15 mg/kg PO q6H OR Azithromycin 15 mg/kg PO on Day 1, then 7.5 mg/kg PO Day 2-5; OR 15 mg/kg PO q24H for 3 days

Non Cystic Fibrosis Bronchiectasis

 
Patient with no previous bacteriology result.

 
Co-amoxiclav 25 mg/kg (Amoxicillin component) IV q8H

 
Cefuroxime 25 - 50 mg/kg IV q6 - 8H
OR
Ceftriaxone 25 - 50 mg/kg IV q12 - 24H
 
Follow the most recent sputum bacteriology result in deciding which antibiotics to use.

The total duration of antibiotics should be for 14 days.

Azithromycin 5 mg/kg EOD is also used in these patient groups especially when there are frequent exacerbations and decline in lung function.








 
In patients chronically colonized with Pseudomonas aeruginosa (2 consecutive positive cultures or 3 positive cultures in 1 year)

 
Addition of nebulized Amikacin for 1 to 3 months should be considered:
Age
Dose
< 1 year 62.5 mg BD
< 6 years 125 mg BD
6 - 12 years 250 mg BD
> 12 years 500 mg BD

Cystic Fibrosis Antibiotic Prophylaxis

 
Oral Antibiotic Prophylaxis


Cloxacillin:
< 10 kg: 125 mg BD
10 - 15 kg: 250 mg BD
> 15 kg: 25 mg/kg BD

Azithromycin:
< 15 kg: 10 mg/kg OD (M,W,F)
15 - 40 kg: 250 mg OD (M,W,F)
> 40 kg: 500 mg OD (M,W,F)

   
The aim of prophylactic Cloxacillin is to reduce Staphylococcus aureus infection and subsequent inflammation during the time of lung development when the lung is most vulnerable. It is used in ALL children below 5 years old or in children > 5 years when there are more than 2 isolates of Staphylococcus aureus in a year.
 
Nebulized antibiotic as prophylactic treatment
P. aeruginosa
B cepacia



















P.aeruginosa only


 
Nebulized Amikacin:
Age Dose
< 1 year 62.5 mg BD
1 - 5 years 125 mg BD
6 - 12 years 250 mg BD
> 12 years 500 mg BD

OR

Nebulized Colomycin (Colistin):
Age Dose
< 2 years 500,000
units BD
2 - 8 years 1,000,000 units BD
> 8 years 2,000,000 units BD
1,000,000 units = 1 Mega units



Nebulized Gentamicin:
Age Dose
< 2 years 20 mg BD
2 - 8 years 40 mg BD
> 8 years 80 mg BD
1,000,000 units = 1 Mega units

OR

Nebulized Tobramycin
150 mg BD
Licensed > 6 years only

   
To be used for 3 months









However, use half these Colistin doses if still combined with Gentamicin.

Bronchospasm can be reduced by:
i) Diluting with water
ii) Pre-dose with bronchodilator. First dose in hospital 








To be used for 3 months







Tobramycin is not available in UMMC

Infective Pulmonary Cystic Fibrosis Exacerbation


Staph aureus


If patient is on prophylaxis dosing, then double the dose of Cloxacillin for 2 weeks (out-patient).

If patient is unwell and requires admission to hospital, then use Cloxacillin 15 - 50 mg/kg IV q6H.

   

Streptococcus pneumonia
Haemophilus Influenza

 
Inpatient:
Co-amoxiclav 25 mg/kg (Amoxicillin component) IV q8H for 2 weeks


Outpatient:
Co-amoxiclav 15 - 25 mg/kg (Amoxicillin component) PO q12H
OR
Cefuroxime 10 - 15 mg/kg PO q12H for 2 weeks

 
 
Pseudomonas aeruginosa

1st isolate:
Ciprofloxacin:
<1 month old: 15 mg/kg BD
>1 month old: 20 mg/kg BD
(max dose 750 mg BD)
+
Nebulised Gentamicin / Amikacin / Tobramycin for 3 months

Re-culture the sputum after 3 weeks. If positive, admit for a 2 week course of dual therapy intravenous antibiotics:
Ceftazidime 50 mg/kg IV q8H (max 9 gm/day)
+
Amikacin 30 mg/kg (max 2 gm) IV q24H

 
High strength sunblock is recommended as photosensitization can occur. Joint pains are seen occasionally due to tendonitis and tendon rupture






If the repeat sputum is negative for PA, then stop the oral Ciprofloxacin and continue nebulized Amikacin / Gentamicin / Tobramycin for a total of 3 months.

If eradication therapy fails, consider nebulized tobramycin as an alternative. 
For Amikacin, send sample for TDM at 3rd dose

If there is a substantial pseudomonal free period (> 3 months), the patient is treated in same manner as 1st isolate.

 
Chronic Pseudomonas Infection (Defined as 3 positive cultures at least 2 months apart and within 1 year)

 
During minor pulmonary exacerbations, 
Ciprofloxacin
< 1 month: 15 mg/kg q12H
> 1 month: 20 mg/kg q12H
(max 750 mg q12H) for 2 weeks

During a severe pulmonary exacerbation or if the patient is admitted for tuning,
intravenous antibiotics: Ceftazidime and Gentamicin / Amikacin / Tobramycin
for 2 weeks.
Followed by nebulized Amikacin / Gentamicin / Tobramycin for 3 months.

If the patient does not improve with Ceftazidime, consider Meropenem, Colistin or Aztreonam.

Colistin 20,000 - 25,000 units/kg IV q8H

 



















Aztreonam 75 mg/kg IV q8H (max 8 gm/day)

Tobramycin 10 mg/kg/day IV q24H (max 600 mg/day).
 
Once chronic infection is established, there is a trend for the pseudomonas to become mucoid and more resistant to antibiotics. The aim of further treatment is to reduce the colony numbers in order to suppress the inflammatory response.

For chronically colonized patient, alternating treatment of nebulized antibiotics (Gentamicin / Amikacin / Tobramycin / Colistin / Aztreonam lysine) can be used.
 








Nebulised Azteronam licensed > 6 years old with dose 75 mg q8H (alternate month).

Aztreonam & Tobramycin are not available in UMMC.
 
Burkholderia Capecia

 
Dual intravenous antibiotics for 2 weeks:
Ceftazidime 50 mg/kg IV q8H (max 9 gm/day)
AND
Meropenem 20 - 40 mg/kg q8H (max 2 gm TDS)
OR  
Timentin 80 - 100 mg/kg q6H (max 3.2 gm q6H) (Ticarcillin / Clavulanic acid)

   
If this is isolated, a further sample is taken to ensure correct result.






Timentin is not available in UMMC.

Stenotrophomonas maltophilia

Co-trimoxazole 5 mg/kg (as Trimethoprim) (max 160 mg) PO q6H for 4 weeks as outpatient.

During acute exacerbation phase:
Co-trimoxazole 5 mg/kg (as Trimethoprim) (max 160 mg) IV q6H
OR Levofloxacin 5 - 10 mg/kg IV q12 - 24H

   





Ideally, combination of 2 antibiotic is needed. 

IV Levofloxacin is not available in UMMC.
 
MRSA

 
Stable patient:
Sodium Fusidate 10 - 15 mg/kg (250 - 500 mg) PO q8H
+ Rifampicin 10 mg/kg PO q12H (max 600 mg/day)
for 2 weeks

 
Linezolid may be used in isolation for 2 weeks.
< 12 years: 10 mg/kg (max 600 mg) q8H
> 12 years: 600 mg q12H
 
Surface swabs are taken for surveillance which includes right and left nostril, perineum and sputum

If the patient has MRSA in the nasal carriage, it is treated with topical Mupirocin / Bactroban to anterior nares. Patients will have to use Chlorhexidine wash on the skin once daily for 5 days.

Following treatment, sputum samples are obtained and repeated bi-monthly.
If positive on 2nd screen, oral treatment is repeated.
If remains positive following 2 full courses of oral treatment or during an infective exacerbation, then consider admission IV Vancomycin for 14 days.


Allergy Bronchopulmonary Aspergilosis


Oral Corticosteroids:
Prednisolone 2 mg/kg/day for 2 weeks, reduced to 1 mg/kg/day for 2 weeks, then alternate 1 mg/kg/day for 2 weeks.
Wean slowly over next 4 months reducing dose by 2.5 mg / 5 mg every 2 weeks.

May need a slow wean to allow adrenal function to return

PLUS
Itraconazole
1 month - 12 years: 5 mg/kg PO q12H (max 200 mg q12H)
> 12 years: 200 mg PO q12H

Nebulised Amphotericin B (non-liposomal) may be used in difficult cases at a dose of 5 - 10 mg q12H after physiotherapy
< 10 years: 5 mg q12H
> 10 years: 10 mg q12H


Pulsed Methylprednisolone 

Methylprednisolone
10 - 15 mg/kg (max 1 gm/dose) IV q24H for 3 days every month.









Voriconazole as a 2nd line agent for patients who have not responded to or cannot tolerate twice daily Itraconazole.

2 - 11 years: 9 mg/kg (max 350 mg) q12H
12-14 years:
< 50 kg – 9 mg/kg (max 350 mg) q12H
> 50 kg – 400 mg q12H for 2 doses then 200 mg q12H (max 300 mg q12H)
15 years and above:
< 40 kg – 200 mg q12H for 2 doses then 100 mg q12H (max 150 mg q12H)
> 40kg – 400 mg q12H for 2 doses then 200 mg q12H (max 300 mg q12H)


The response to treatment is monitored by checking pulmonary function tests, CXRs and watching IgE titre as this should fall over time to more normal levels.











Monitor liver function and continue Itraconazole while they remain on steroids. Monitor Itraconazole levels after 14 days of treatment (range: 5 - 15 mg/L)
 
Invasive Aspergillus


IV Caspofungin
<3 months: 25 mg/m2 q24H
3 months - 1 year: 50 mg/m2 q24H
>1 year: 70 mg/m2 q24H (max 70 mg) Day 1, then 50 mg/m2 q24H (max 50 mg).

This can be increased to 70 mg/m2 q24H (max 70 mg) if lower dose is tolerated but inadequate response.