Antibiotics for community acquired pneumonia in adult outpatients

Authors

  • T Verheij,

    Chairman, Corresponding author
    1. University Medical Centre Utrecht, Department of General Practice, Utrecht, NETHERLANDS
    • T Verheij, Chairman, Department of General Practice, University Medical Centre Utrecht, Universiteitsweg 100, Utrecht, 3584 CG, NETHERLANDS. t.j.m.verheij@med.uu.nl.

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  • M Kochen,

  • IM Hoepelman,

  • JW Lammers,

  • J Macfarlane,

  • M Woodhead


Background

Studies on the aetiology of community-acquired pneumonia (CAP) show that on average 35% is caused by Streptococcus pneumoniae, 10% by Haemophilus influenza and variable percentages by other pathogens like Mycoplasma pneumoniae, Chlamydia pneumoniae, Legionella species and viruses.ERS Task Force There is no discussion about the question whether a patient with a CAP should be given antibiotic treatment, but there are different views on which antimicrobial therapy is indicated for the different subgroups of patients.British Thoracic Soc, Niederman Based on the differences in prognosis the American Thoracic Society mentioned four subgroups of patients with CAP in their guidelines on the management of CAP:
·.Outpatient pneumonia without comorbidity and younger than 60 years of age.
·.Outpatient pneumonia with comorbidity and/or older than 60 years of age.
·.Hospitalised patients with CAP.
·.Severe hospitalised CAP.
Several studies have shown that besides old age, comorbidity like chronic obstructive lung disease, diabetes mellitus and congestive heart failure are important factors with regard to the occurrence of complications and mortality.Fine, Torres Whether the etiology of CAP in these high-risk patients differs from the first subgroup mentioned above, in so far that the chance of finding gram-negative bacilli. Moraxella catharralis and Mycobacterium tuberculosis is higher, is under discussion. Patients in subgroup 3 are usually above 60 years of age and have comorbidity. In this subgroup the chance that aerobic gram-negatives, Legionella species and polymicrobial infections have caused the respiratory infection is probably clinically relevant. The etiology in the fourth subgroup is probably more or less the same as in the third but because of the severity of the clinical symptoms antimicrobial therapy should be more intensive. This review will be on treatment of adult outpatients only. The discussion on the choice of antimicrobial agents in adults with CAP is partially due to the occurrence of resistance in the different countries. In this review effectiveness of the different antimicrobial therapies will be discussed in relation with possible absence and presence of resistance of the possible pathogens.

Objectives

The aim of this review is to assess the effectiveness of the different antimicrobial therapies in adult outpatients with CAP.

Criteria for considering studies for this review

Types of studies

All randomised trials on the effectiveness of antibiotics in adult outpatients with CAP on improvement on clinical parameters, cure rates and mortality.

Types of participants

Outpatients over 17 years of age. We will consider studies in which outpatients meet pre-defined criteria for CAP as defined by the British Thoracic Society. They defined CAP in outpatients as follows:

Clinical definition, in the absence of a chest X-ray
· Symptoms of an acute LRT infection including both (a) cough and at least one other LRT symptom and (b) at least one systemic feature; either a symptom complex of sweating, fevers, shivers, aches and pains and/or temperature D38°C.
· New focal chest signs on examination
· No other explanation for the illness, which is treated as pneumonia with antibiotics.

Definition when a chest X-ray is available
· Symptoms and signs consistent with an acute lower respiratory tract infection
· Associated with new radiographic shadowing for which there is no other explanation (e.g. not pulmonary oedema or infarction)
· The illness is the primary clinical problem and is managed as pneumonia

Studies on patients initially hospitalised will be excluded.

Types of intervention

Although there may be some older placebo-controlled studies, the perceived efficacy of antibiotics in pneumonia means that most of the available research deals with comparisons of one antibiotic with another. Most comparisons of intravenous versus intravenous and intravenous versus oral application of drugs are done in a hospital setting. However the latter approach might occasionally be performed in an ambulatory setting. Therefore we will include trials of antibiotic versus placebo, oral antibiotic versus different oral antibiotics, parenteral versus oral and single drug vs. combinations of oral antbiotic regimens in outpatients. We will also search for trials that compare outcomes in outpatients treated empirically with those guided by radiological and/or microbiological investigations.

Trials which allow concurrent use of other medications such as antitussives, antipyretics, bronchodilators, or mucolytics will be included if they allowed equal access to such medications for patients in both arms of the trial.

Antimicrobial agents are classified according to the British National Formulary (BNF 9/99)
1. Penicillins
2. Cephalosporins and other beta-lactam antibiotics
3. Tetracyclines
4. Aminoglycosides
5. Macrolides
6. Clindamycin
7. Some other antibiotics
8. Sulphonamides and trimethoprim
9. Metronidazole and tinidazole
10. Quinolones

Types of outcome measures

1. Clinical response. Where possible, duration of clinical parameters will be used as outcome measures. Also, where possible, continuous data such as time to recovery will be converted to dichotomous outcomes (cured or not cured at a specified time point). Since pneumonia-related hospitalization usually occurs within 10 days of initial presentation (Minogue) and mean duration of antimicrobial therapy ranged from 11 to 13 days for outpatients in a large study (Gilbert) e.g. 14 days after initial presentation might be an appropriate point in time. We will use a clinical definition of cure since radiographic resolution lags behind clinical improvement (Macfarlane).
2. Frequency of hospitalization.
3. Mortality

Search strategy for identification of studies

See: Unavailable search strategy

The Cochrane Acute Respiratory Infections Group's trial register, The
Cochrane Library, and MEDLINE (1998-1999) will be searched using the
following terms: exploded MeSH headings COMMUNITY ACQUIRED INFECTION,
PNEUMONIA, RESPIRATORY TRACT INFECTION, ANTIBIOTICS.
Studies will also be identified by checking the bibliographies of all
studies and review articles retrieved, and by contacting the first or
corresponding authors of all included studies. To identify any aditional
published or unpublished studies we will contact the following
manufacturers: SmithKline Beecham, Pfizer, Yamanouchi, Bristol-Myers
Squibb, Lilly, Merck, Sharp & Dohme.

Methods of the review

Data to be extracted from each study if possible):

· description of participants (al outpatients over 17 years)
·.description of potential pathogens found and their antimicrobial resistance
-description of intervention
· description of control therapy
· total number of participants in each arm of the trial
·.study setting
·.mean duration of symptoms in each arm of the trial
· cure rates in each arm of the trial
· proportion of patients admitted to hospital in each arm of th trial
· mortality rates in each arm of the trial

Analysis: Homogeneity will be tested using RevMan. For the dichotomous data an estimate of the common odds ratios with approximate 95% confidence intervals will be estimated using the Mantel-Haenzel approach. When this is not possible a weighted average of median survival duration across studies will be calculated. Sensitivity analysis will be performed excluding studies of low methodological quality, excluding unpublished studies, excluding or including studies where there id some ambiguity as to whether they meet the inclusion criteria. Publication bias will be assessed by using a "funnel plot". Subgroup analyses will be done for different age categories, for patients with different chronic diseases, and, if possible, according to bacterial etiology and antimicrobial resistance rates.

Methodological quality of included studies
Table 1 shows the specific criteria for methodological quality assessment, consisting of internal validity criteria, descriptive criteria and statistical criteria. The descriptive and statistical criteria refer to the external validity of the study and are necessary for subgroup and sensitivity analyses. This criteria list is a modified version of a list that already has been used in a number of systematic reviews in the field of physiotherapy Windt, Heijden, Tulder, Vet and includes all criteria of the list of Jadad et al. Jadad, Schulz et al.Schulz and Verhagen et al. Verhagen.

Table 1:

MAASTRICHT - AMSTERDAM CONSENSUS LIST

PATIENT SELECTION
a. Were the eligibility criteria specified?
b. Treatment allocation
1) Was a method of randomisation performed?
2) Was the treatment allocation concealed?
c. Were the group similar at baseline regarding the most important prognostic indicators?

INTERVENTION
d. Were therapeutic and control interventions operationalized?
e. Was the careprovider blinded?
f. Was controlled for co-interventions which could explain the results?
g. Was the compliance rate (in each group) unlikely to cause bias?
h. Was the patient blinded?

OUTCOME MEASUREMENTS
i. Was the outcome assessor blinded?
j. Were the most important outcome parameters applied?
k. Was there a description of adverse effects?
l. Was the withdrawal/drop-out rate unlikely to cause bias?
m. Timing follow-up measurements
1) Was a short-term follow-up measurement performed?
2) Was a long-term follow-up measurement performed?
n. Was the timing of outcome assessment in both groups comparable?

STATISTICS
o. Was the sample size for each group described?
p. Did the analysis include an intention-to-treat analysis?
q. Were the points estimates and measures of variability presented for the primary outcome measures?

The studies will be assessed by 4 reviewers. Disagreement will be resolved by discussion. Studies will not be blinded.

Potential conflict of interest

No potential conflicts of interest to declare.

Sources of support

External sources of support

  • No sources of support supplied

Internal sources of support

  • No sources of support supplied

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