Antibiotic strategies in lower respiratory tract infections

Antibiotic Strategy in Lower

Respiratory Tract Infections

Gamal Rabie Agmy, MD, FCCP Professor of Chest Diseases , Assiut University

ANTIMICROBIAL DRUGS

MECHANISMS OF ACTION OF

ANTIBACTERIAL DRUGS

Mechanism of action include: Inhibition of cell wall

synthesis

Inhibition of protein synthesis

Inhibition of nucleic acid synthesis

Inhibition of metabolic pathways

Interference with cell membrane integrity

Antibacterial spectrum—Range of activityof an antimicrobial against bacteria. Abroad-spectrum antibacterial drug caninhibit a wide variety of gram-positive andgram-negative bacteria, whereas anarrow-spectrum drug is active onlyagainst a limited variety of bacteria.

Bacteriostatic activity—-The level ofantimicro-bial activity that inhibits thegrowth of an organism. This is determinedin vitro by testing a standardizedconcentration of organisms against aseries of antimicrobial dilutions. Thelowest concentration that inhibits thegrowth of the organism is referred to asthe minimum inhibitory concentration(MIC).

Bactericidal activity—The level ofantimicrobial activity that kills the testorganism. This is determined in vitro byexposing a standardized concentration oforganisms to a series of antimicrobialdilutions. The lowest concentration thatkills 99.9% of the population is referred toas the minimum bactericidalconcentration (MBC).

Antibiotic combinations—Combinations ofantibiotics that may be used (1) to broadenthe antibacterial spectrum for empirictherapy or the treatment of polymicrobialinfections, (2) to prevent the emergence ofresistant organisms during therapy, and (3)to achieve a synergistic killing effect.

Antibiotic synergism—Combinations oftwo antibiotics that have enhancedbactericidal activity when tested togethercompared with the activity of eachantibiotic.

Antibiotic antagonism—Combination ofantibiotics in which the activity of oneantibiotic interferes With the activity of theother (e.g., the sum of the activity is lessthan the activity of the individual drugs).

Beta-lactamase—An enzyme thathydrolyzes the beta-lactam ring in thebeta-lactam class of antibiotics, thusinactivating the antibiotic. The enzymesspecific for penicillins and cephalosporinsaret he penicillinases andcephalosporinases, respectively.

32 ug/ml 16 ug/ml 8 ug/ml 4 ug/ml 2 ug/ml 1 ug/ml

Sub-culture to agar medium MIC = 8 ug/ml

MBC = 16 ug/ml

Minimal Inhibitory Concentration (MIC)

vs.

Minimal Bactericidal Concentration (MBC)

REVIEW

Patterns of Microbial Killing

Concentration dependent

– Higher concentration greater killing Aminoglycosides, Flouroquinolones, Ketolides, metronidazole, Ampho B.

Time-dependent killing

– Minimal concentration-dependent killing (4x MIC)

– More exposure more killing Beta lactams, glycopeptides, clindamycin, macrolides, tetracyclines, bactrim

EFFECTS OF

COMBINATIONS OF DRUGS

Sometimes the chemotherapeutic effects of two drugs given simultaneously is greater than the effect of either given alone.

This is called synergism. For example, penicillin and streptomycin in the treatment of bacterial endocarditis. Damage to bacterial cell walls by penicillin makes it easier for streptomycin to enter.

EFFECTS OF


Other combinations of drugs can be antagonistic.

For example, the simultaneous use of penicillin and tetracycline is often less effective than when wither drugs is used alone. By stopping the growth of the bacteria, the bacteriostatic drug tetracycline interferes with the action of penicillin, which requires bacterial growth.

EFFECTS OF


Combinations of antimicrobial drugs should be used only for:

1. To prevent or minimize the emergence of resistant strains.

2. To take advantage of the synergistic effect.

3. To lessen the toxicity of individual drugs.

Resistance

Physiological Mechanisms

1. Lack of entry – tet, fosfomycin

2. Greater exit

efflux pumps

tet (R factors)

3. Enzymatic inactivation

bla (penase) – hydrolysis

CAT – chloramphenicol acetyl transferase

Aminogylcosides & transferases REVIEW

Resistance

Physiological Mechanisms

4. Altered target

RIF – altered RNA polymerase (mutants)

NAL – altered DNA gyrase

STR – altered ribosomal proteins

ERY – methylation of 23S rRNA

5. Synthesis of resistant pathway

TMPr plasmid has gene for DHF reductase; insensitive to TMP

(cont’d)

REVIEW

Pneumonia

Scores

Each risk factor scores one point with a

maximum score of 5.

Confusion of new onset

Urea > 7 mmol/L

Respiratory rate >30/min or greater

Blood pressure <90 mmHg systolic or <65

mmHg diastolic

Age >65 years

CURB-65

The risk of death at 30 days increases as the

score increases:

0 - 0.7%

1 - 3.2%

2 - 13.0%

3 - 17.0%

4 - 41.5%

5 - 57.0%

CURB-65

Disposition recommendations based on

score:

0-1: Treat as an outpatient

2-3: Consider a short stay in hospital or watch

very closely as an outpatient

4-5: Requires hospitalization, consider ICU

admission

CURB-65

19

CURB 65 Rule – Management of CAP

CURB 65

Confusion

BUN > 30

RR > 30

BP SBP <90

DBP <60

Age > 65

CURB 0 or 1 Home Rx

CURB 2 Short Hosp

CURB 3 Medical Ward

CURB 4 or 5 ICU care


maximum score of 4.




mmHg diastolic

Age >65 years

CRB-65

21

CRB 65 Rule – Management of CAP

CRB 65

Confusion

RR > 30

BP SBP <90

DBP <60

Age > 65

CRB 0 or 1 Home Rx

CRB 2 Short Hosp

CRB 3 Medical

Ward

CRB 4 ICU care


maximum score of 8.


Urea > 7 mmol/L



mmHg diastolic

Age >65 years

LDH > 230 u/L

Albumin <3.5 g/dL

Platelet count <100 × 109/L

Expanded CURB-65

The expanded-CURB-65 score was

categorized into three classes as follows: 0–

2 as low risk, 3–4 intermediate risk, and 5–8

high risk. Accordingly, patients with one of

three tiers of scores should be treated either as

outpatient, or inpatients in hospital ward or

ICU, respectively.

Expanded CURB-65

0–2 2.57% mortality



Expanded CURB-65

This is a more complex scoring system which

stratifies patients into low, moderate or high

risk, advocating outpatient treatment for those

in the low risk group.

Pneumonia Severity Index (PSI)

A patient can only be in the low risk group if they

satisfy the following criteria:

1-Age >50,

2-No malignancy, CCF, cerebrovascular, renal or

liver disease,

3-Normal mental state,

4-Satisfactory vital signs: HR<125, RR <30, systolic

BP >90 mmHg, temp 35-40C

Pneumonia Severity Index (PSI)

27

PORT Scoring – PSI

Clinical Parameter Scoring

Age in years Example

For Men (Age in yrs) 50

For Women (Age -10) (50-10)

NH Resident 10 points

Co-morbid Illnesses

Neoplasia 30 points

Liver Disease 20 points

CHF 10 points

CVD 10 points

Renal Disease (CKD) 10 points

Clinical Parameter Scoring

Clinical Findings

Altered Sensorium 20 points

Respiratory Rate > 30 20 points

SBP < 90 mm 20 points

Temp < 350 C or > 400 C 15 points

Pulse > 125 per min 10 points

Investigation Findings

Arterial pH < 7.35 30 points

BUN > 30 20 points

Serum Na < 130 20 points

Hematocrit < 30% 10 points

Blood Glucose > 250 10 points

Pa O2 10 points

X Ray e/o Pleural Effusion 10 points

Pneumonia Patient Outcomes

Research Team (PORT)

28

Classification of Severity - PORT

Predictors Absent

Class I

70

Class II

71 – 90

Class III

91 - 130

Class IV

> 130

Class V

29

CAP – Management based on PSI Score

PORT Class PSI Score Mortality % Treatment Strategy

Class I No RF 0.1 – 0.4 Out patient

Class II 70 0.6 – 0.7 Out patient

Class III 71 - 90 0.9 – 2.8 Brief hospitalization

Class IV 91 - 130 8.5 – 9.3 Inpatient

Class V > 130 27 – 31.1 IP - ICU

Recent Australian studies have developed

severity scoring systems (eg CORB, SMART-

COP) that are based on predictors of

requirement for intensive respiratory or

inotrope support, in addition to mortality. The

CORB score is simpler and does not rely on

investigation results however it is less sensitive

than SMART-COP.

CORB and SMART-COP

Confusion (acute)

Oxygen saturation 90% or less

Respiratory rate > 30 breaths per minute

Blood pressure < 90 mm Hg (systolic) or < 60

mm Hg (diastolic)

'Severe CAP' is defined as the presence of at

least two of these features and has a sensitivity

of 81% and specificity of 68% for predicting

need for IRVS.

CORB

SMART-COP

SMART-COP

Interpretation of SMART-COP score:

0 to 2 points—low risk of needing intensive

respiratory or vasopressor support (IRVS)

3 to 4 points—moderate risk (1 in 8) of needing

IRVS

5 to 6 points—high risk (1 in 3) of needing IRVS

7 or more points—very high risk (2 in 3) of needing

IRVS

Severe CAP = a SMART-COP score of 5 or more

points

SMART-COP

0–2 5.48 % mortality



A-DROP

It was developed in Japan

Age, Dehydration, Respiratory failure, Orientation

disturbance, Systolic blood pressure.

0-1 Low risk Home treatment

2 Intermediate risk Hospitalization

3-5 High risk ICU admission

A-DROP


2 16.07 % mortality

3-5 41.77 % mortality

37

CAP – The Two Types of Presentations

Classical

• Sudden onset of CAP

• High fever, shaking chills

• Pleuritic chest pain, SOB

• Productive cough

• Rusty sputum, blood tinge

• Poor general condition

• High mortality up to 20% in

patients with bacteremia

• S.pneumoniae causative

• Gradual & insidious onset

• Low grade fever

• Dry cough, No blood tinge

• Good GC – Walking CAP

• Low mortality 1-2%; except

in cases of Legionellosis

• Mycoplasma, Chlamydiae,

Legionella, Ricketessiae,

Viruses are causative

Atypical

38

Empiric Treatment – Outpatient

Healthy and no risk factors for DR S.pneumoniae

1. Macrolide or Doxycycline

Presence of co-morbidities, use of antimicrobials

within the previous 3 months, and regions with a

high rate (>25%) of infection with Macrolide

resistant S. pneumoniae

1. Respiratory FQ – Levoflox, Gemiflox or Moxiflox

2. Beta-lactam (High dose Amoxicillin, Amoxicillin-

Clavulanate is preferred; Ceftriaxone, Cefpodoxime,

Cefuroxime) plus a Macrolide or Doxycycline

39

Empiric Treatment – Inpatient – Non ICU

1. A Respiratory Fluoroquinolone (FQ) or

2. A Beta-lactam plus a Macrolide (or Doxycycline)

(Here Beta-lactam agents are 3 Generation

Cefotaxime, Ceftriaxone, Amoxiclav)

3. If Penicillin-allergic Respiratory FQ or

Ertapenem is another option

40

Empiric Treatment: Inpatient in ICU

1. A Beta-lactam (Cefotaxime, Ceftriaxone,

or Ampicillin-Sulbactam) plus

either Azithromycin or Fluoroquinolone

2. For penicillin-allergic patients, a respiratory

Fluoroquinolone and Aztreonam

41

Empiric Rx. – Suspected Pseudomonas

1. Piperacillin-Tazobactam, Cefepime, Carbapenums

(Imipenem, or Meropenem) plus either Cipro or Levo

2. Above Beta-lactam + Aminoglycoside + Azithromycin

3. Above Beta-lactam + Aminoglycoside + an

antipseudomonal and antipneumococcal FQ

4. If Penicillin allergic - Aztreonam for the Beta-lactam

42

Empiric Rx. – CA MRSA

For Community Acquired Methicillin-Resistant

Staphylococcus aureus (CA-MRSA)

Targocid,Vancomycin or Linezolid

For Methicillin Sensitive S. aureus (MSSA)

B-lactam and sometimes a respiratory

Fluoroquinolone, (until susceptibility results).

Switching from intravenous to oral

Patients treated initially with parenteral

antibiotics should be transferred to an oral

regimen when they are hemodynamically stable

and improving clinically, are able to ingest

medications, and have a normally functioning

gastrointestinal tract.

Duration of the Treatment:

Patients with CAP should be treated for a

minimum of 5 days, should be afebrile for 48–72

h, and should have no more than 1 CAP-

associated sign of clinical instability before

discontinuation of therapy. Lengthening of

therapy to a minimum of 14 days is

recommended in some cases according to

severity.

Criteria for clinical stability

Temperature≤37.8_C

Heart rate ≤100 beats/min

Respiratory rate≤24 breaths/min

Systolic blood pressure ≥90 mm Hg

Arterial oxygen saturation ≥90% or pO2 ≥60

mm Hg on room air

Ability to maintain oral intake*

Normal mental status*

What to Do When a Patient with Community

Acquired Pneumonia Fails to improve?

Chest sonography

Chest sonography

http://radiographics.rsnajnls.org/cgi/content/full/20/3/653/F6B

Post-stenotic pneumonia Posterior intercostal scan shows a

hypoechoic consolidated area that contains

anechoic, branched tubular structures in the

bronchial tree (fluid bronchogram).

Chest sonography

Chest sonography

http://radiographics.rsnajnls.org/cgi/content/full/22/1/e1/F3A

http://radiographics.rsnajnls.org/cgi/content/full/22/1/e1/F3C

http://intl-radiographics.rsnajnls.org/cgi/content/full/20/3/653/F12A

Chest CT

Chest CT can detect pleural effusion, lung abscess, or

central airway obstruction, all of which can cause

treatment failure.

It may also detect noninfectious causes such as

bronchiolitis obliterans organizing pneumonia .

Since empyema and parapneumonic effusion can

contribute to nonresponse, thoracentesis should be

performed in all nonresponding patients with

significant pleural fluid accumulation.

Chest CT

Bronchoscopy

Bronchoscopy can evaluate the airway for

obstruction due to a foreign body or

malignancy, which can cause a postobstructive

pneumonia.

Protected brushings and bronchoalveolar lavage

(BAL) may be obtained for microbiologic and

cytologic studies; in some cases, transbronchial

biopsy may be helpful.

Bronchoscopy

In addition, BAL may reveal evidence of

noninfectious disorders or, if there is a

lymphocytic rather than neutrophilic

alveolitis, viral or Chlamydia infection

Thoracoscopic lung biopsy

Thoracoscopic or open lung biopsy may be

performed if all of these procedures are

nondiagnostic and the patient continues to be ill.

The advent of thoracoscopic procedures has

significantly reduced the need for open lung

biopsy and its associated morbidity.

AECOPD Most exacerbations of COPD are caused by

viral or bacterial infection. Approximately 50%

of exacerbations are caused by bacterial

infection. Mild to moderate exacerbations is

often caused by Haemophilus influenzae,

Streptococcus pneumoniae, Moraxella

catarrhalis,

A severe exacerbation is often caused by

Pseudomonas aeruginosa and Enterobacteriacea

AECOPD Sputum cultures should not be routinely performed

expect in patients with frequent exacerbations,

worsening clinical status or inadequate response

after 72 hours on initial empiric antibiotic, and /or

exacerbation requiring mechanical ventilation

Uncomplicated AECOPD

H. influenzae

S. pneumoniae

M. catarrhalis

• Floroquinolones

• Advanced macrolide

(azythromycin, clarithromycin)

• Cephalosporins 2nd or 3rd

generation

Complicated AECOPD

As in Uncomplicated

AECOPD plus presence

of resistant organisms (s

– lactamase producing,

penicillin-resistant S.

pneumoniae), Entero-

bacteriaceae (K.

pneumoniae, E. coli,

Proteus, Enterobacter,

etc)

ß-lactam/ß-lactamase

inhibitor (Co-amoxiclav,

ampicillin/ sulbactam)

• Fluoroquinolone

(Gemifloxacin,

Levofloxacin,

Moxifloxacin)

Complicated AECOPD

As in complicated

AECOPD plus

P. aeruginosa Fluoroquinolone

(Ciprofloxacin,

Levofloxacin –

high dose^)

• Piperacillin-

tazobactam

P. aeruginosa should be considered

in the presence of at least two of the

following [recent hospitalization, frequent

(>4 courses per year) or recent

administration of antibiotics (last 3 months),

severe disease (FEV1 < 30%), oral steroid

use (>10 mg of prednisolone daily in the last

2 weeks)].

Risk factors for poor outcome in

patients with AECOPD

presence of comorbid diseases, severe

COPD, frequent exacerbations (>3/yr), and

antimicrobial use within last 3 months.

VAP a new or progressive and persistent radiographic

abnormality developing in a patient on mechanical

ventilation (or within 48 hours of mechanical

ventilation), who must also demonstrate: one or more

systemic signs (fever, leukopenia or leukocytosis, or

altered mental status in those >70 years of age) and

selected pulmonary criteria (eg, change in respiratory

secretions, new onset of cough, dyspnea, rales,

bronchial breath sounds, or worsening oxygenation).

Additional criteria were available for reporting VAP

with laboratory evidence of infection and for VAP in

immuno-compromised patients.

Ventilator Associated Events

all the conditions that result in a significant and sustained

deterioration in oxygenation, defined as a greater than

20% increase in the daily minimum fraction of inspired

oxygen or an increase of at least 3 cm H2O in the daily

minimum positive end-expiratory pressure (PEEP) to

maintain oxygenation. It is imperative to understand that

both infectious conditions (such as tracheitis,

tracheobronchitis, and pneumonia) and noninfectious

conditions (such as atelectasis, pulmonary embolism,

pulmonary edema, ventilator-induced lung injury, and

others) may fulfill this VAE


Tier 1: ventilator-associated condition (VAC) —the

patient develops hypoxemia (as defined above) for a

sustained period of more than 2 days. The etiology of the

hypoxemia is not considered.

Tier 2: infection-related ventilator-associated complication

(IVAC) —hypoxemia develops in the setting of generalized

infection or inflammation, and antibiotics are instituted for a

minimum of 4 days.


Tier 3: probable or possible ventilator-associated

pneumonia (VAP) —additional laboratory evidence of

white blood cells on Gram stain of material from a

respiratory secretion specimen of acceptable quality, or

(=possible)/and (=probable) presence of respiratory

pathogens on quantitative cultures, in patients with IVAC.

Additional criteria are also available for use in meeting the

possible or probable VAP definitions.

Threshold values for cultured specimens used

in the diagnosis of pneumonia

Specimen collection/technique Values†

Lung tissue >104 CFU/g tissue

Bronchoscopically (B) obtained specimens

Bronchoalveolar lavage (B-BAL) >104 CFU/ml

Protected BAL (B-PBAL) >104 CFU/ml

Protected specimen brushing (B-PSB) >103 CFU/ml

Nonbronchoscopically (NB) obtained (blind)

specimens

Mini-BAL >104 CFU/ml

Sputum Mild,mod, Severe growth

CDC/NHSN Pneumonia (Ventilator-associated [VAP] and non-ventilator-associated Pneumonia [PNEU]) Event. January 2015, modified April 2015.

Clinical Pulmonary Infection Score (CPIS)

CPIS

TREATMENT OF VENTILATOR-

ASSOCIATED

TRACHEOBRONCHITIS

Should Patients With Ventilator-

Associated Tracheo-bronchitis (VAT)

Receive Antibiotic Therapy?

• Not providing antibiotic therapy (weak

recommendation, low-quality evidence).

INITIAL TREATMENT OF VAP

AND HAP

Should Selection of an Empiric Antibiotic

Regimen for VAP Be Guided by Local

Antibiotic-Resistance Data?

All hospitals regularly generate and disseminate a local antibiogram, ideally

one that is specific to their intensive care population(s) if possible

Empiric treatment regimens be informed by the local distribution of

pathogens associated with VAP and their antimicrobial susceptibilities.

Values and preferences: Targeting the specific pathogens and to assure

adequate treatment.

Remarks: The frequency with which the distribution of pathogens and their

antimicrobial susceptibilities are updated should be determined by the

institution. Considerations should include their rate of change, resources,

and the amount of data available for analysis.

What Antibiotics Are Recommended for Empiric

Treatment of Clinically Suspected VAP?

Coverage for S. aureus, Pseudomonas aeruginosa, and other gram-negative bacilli in all empiric regimens (strong recommendation, low-quality evidence).

i. We suggest including an agent active against MRSA for the empiric treatment of suspected VAP only in patients with any of the following:

a risk factor for antimicrobial resistance (Table 2),

patients being treated in units where >10%–20% of S. aureus isolates are methicillin resistant, and

patients in units where the prevalence of MRSA is not known (weak recommendation, very low-quality evidence).

ii. We suggest including an agent active against methicillin sensitive S. aureus (MSSA) (and not MRSA) for the empiric treatment of suspected VAP in patients without risk factors for antimicrobial resistance, who are being treated in ICUs where <10%–20% of S. aureus isolates are methicillin resistant (weak recommendation, very low-quality evidence).

• 2. If empiric coverage for MRSA - vancomycin or linezolid (strong recommendation, moderate-quality evidence).

• 3. Empiric coverage for MSSA (and not MRSA) - piperacillin-tazobactam, cefepime, levofloxacin, imipenem, or meropenem (weak recommendation, very low-quality evidence). Oxacillin, nafcillin, or cefazolin are preferred agents for treatment of proven MSSA, but are not necessary for the empiric treatment of VAP if one of the above agents is used.

6. In patients with suspected VAP, we suggest avoiding

Colistin / aminoglycosides if alternative agents with

adequate gram-negative activity are available (weak

recommendation, low-quality evidence).

Values and Preferences: These recommendations are a

compromise between the competing goals of providing

early appropriate antibiotic coverage and avoiding

superfluous treatment that may lead to adverse drug

effects, Clostridium difficile infections, antibiotic

resistance, and increased cost.

• If patient has structural lung disease increasing

the risk of gram-negative infection (ie,

bronchiectasis or cystic fibrosis), 2

antipseudomonal agents are recommended.

What Antibiotics Should Be Used for the

Treatment for MRSA HAP/VAP?

• Treat with either vancomycin or linezolid rather than other

antibiotics or antibiotic combinations (strong recommendation,

moderate- quality evidence).

• Remarks: The choice between vancomycin and linezolid may

be guided by patient-specific factors such as blood cell counts,

concurrent prescriptions for serotonin-reuptake inhibitors,

renal function, and cost.

LENGTH OF THERAPY

Should Patients With VAP Receive 7 Days or 8–

15 Days of Antibiotic Therapy?

• 1. For patients with VAP, we recommend a 7-day course of antimicrobial therapy rather than a longer duration (strong recommendation, moderate-quality evidence).

• Remarks: There exist situations in which a shorter or longer duration of antibiotics may be indicated, depending upon the rate of improvement of clinical, radiologic, and laboratory parameters.

What Is the Optimal Duration of Antibiotic

Therapy for HAP (Non-VAP)?

• 7-day course of antimicrobial therapy (strong recommendation, very low quality evidence).

• Remarks: There exist situations in which a shorter or longer duration of antibiotics may be indicated, depending upon the rate of improvement of clinical, radiologic, and laboratory parameters.

Should Antibiotic Therapy Be De-escalated or

Fixed in Patients With HAP/VAP?

• Antibiotic therapy be de-escalated rather than fixed (weak recommendation, very low-quality evidence).

• Remarks: De-escalation refers to changing an empiric broad-spectrum antibiotic regimen to a narrower antibiotic regimen by changing the antimicrobial agent or changing from combination therapy to monotherapy.

• In contrast, fixed antibiotic therapy refers to maintaining a broad-spectrum antibiotic regimen until therapy is completed.

Should Discontinuation of Antibiotic Therapy Be Based

Upon PCT Levels Plus Clinical Criteria or Clinical

Criteria Alone in Patients With HAP/VAP?

• Using PCT levels plus clinical criteria to guide the discontinuation of antibiotic therapy, rather than clinical criteria alone (weak recommendation, low-quality evidence).

• Remarks: It is not known if the benefits of using PCT levels to determine whether or not to discontinue antibiotic therapy exist in settings where standard antimicrobial therapy for VAP is already 7 days or less.

Should Discontinuation of Antibiotic Therapy Be

Based Upon the CPIS Plus Clinical Criteria or

Clinical Criteria Alone in Patients With

Suspected HAP/VAP?

Not using the CPIS to guide the discontinuation of antibiotic therapy (weak recommendation, low-quality evidence).

Lung Abscess Standard treatment of an anaerobic lung infection is clindamycin (600 mg

IV q8h followed by 150-300 mg PO qid).

Although metronidazole is an effective drug against anaerobic bacteria,

metronidazole in treating lung abscess has been rather disappointing

because these infections are generally polymicrobial. A failure rate of 50%

has been reported.

In hospitalized patients who have aspirated and developed a lung abscess,

antibiotic therapy should include coverage against S

aureus andEnterobacter and Pseudomonas species.

Ampicillin plus sulbactam is well tolerated and as effective as clindamycin

with or without a cephalosporin in the treatment of aspiration pneumonia

and lung abscess.

Lung Abscess Expert opinion suggests that antibiotic treatment should be continued until

the chest radiograph has shown either the resolution of lung abscess or the

presence of a small stable lesion.

Patients with lung abscesses usually show clinical improvement, with

improvement of fever, within 3-4 days after initiating the antibiotic therapy.

Defervescence is expected in 7-10 days. Persistent fever beyond this time

indicates therapeutic failure, and these patients should undergo further diagnostic

studies to determine the cause of failure.

Considerations in patients with poor response to antibiotic therapy include

bronchial obstruction with a foreign body or neoplasm or infection with a resistant

bacteria, mycobacteria, or fungi.

A nonbacterial cause of cavitary lung disease may be present, such as lung

infarction, cavitating neoplasm, and vasculitis. The infection of a preexisting

sequestration, cyst, or bulla may be the cause of delayed response to

antibiotics.

Lung Abscess Surgery is very rarely required for patients with uncomplicated lung

abscesses. The usual indications for surgery are failure to respond to medical

management, suspected neoplasm, or congenital lung malformation. The

surgical procedure performed is either lobectomy or pneumonectomy.

When conventional therapy fails, either percutaneous catheter drainage or

surgical resection is usually considered. Endoscopic lung abscess drainage is

considered if an airway connection to the cavity can be demonstrated.

Endoscopic drainage, however, is not without significant risk to the patient

Therapy has several major goals: (1) treatment of infection, particularly during acute exacerbations (2) improved clearance of tracheobronchial secretions (3) reduction of inflammation (4) treatment of an identifiable underlying problem Antibiotics are the cornerstone of bronchiectasis management antibiotics are used only during acute episodes choice of an antibiotic should be guided by Gram's stain and culture of sputum empiric coverage (amoxicillin, co-trimoxazole,levofloxacin) is often given initially Infection with P. aeruginosa is of particular concern, as it appears to be associated with greater rate of deterioration of lung function and worse quality of life There are no firm guidelines for length of therapy, but a 10–14 day course or longer is typically administered facilitate drainage : mechanical methods and devices & appropriate positioning Mucolytic agents to thin secretions and allow better clearance are controversial Aerosolized recombinant DNase, which decreases viscosity of sputum by breaking down DNA released from neutrophils, has been shown to improve

pulmonary function in CF but may be deleterious and should be avoided in bronchiectasis not associated with CF Bronchodilators to improve obstruction and aid clearance of secretions are useful in patients with airway hyperreactivity and reversible airflow obstruction surgical therapy »»»»»»»»»»»»»»»»»»» when bronchiectasis is localized and the morbidity is substantial despite adequate medical therapy massive hemoptysis, often originating from the hypertrophied bronchial circulation conservative therapy, including rest and antibiotics surgical resection bronchial arterial embolization Although resection may be successful if disease is localized, embolization is preferable with widespread disease

Health & Medicine

Antibiotic strategies in lower respiratory tract infections