Drugs 10: 437-450 (1975)

Treatment of Respiratory Infections M.W. Bums St. Vincent's Hospital, Sydney

A respiratory infection can be said to be present when micro-organisms act as irritants to the respiratory tract and cause an obvious host reaction - i.e. in an attempt to reject the irritant. Inflammation is the body's method of rejecting such irritation and is not seen when organisms are acting as mere commensals or innocent passengers. The respiratory tissues are resistant to bacterial invasion and even colonisation and some lowering of resistance appears to be necessary before this can occur. The main cause of such a fall in immunity is viral infection to which the respiratory tract is quite susceptible . Other phenomena such as chronic irritation, anatomical abnormalities, tissue damage or a fall in general resistance are sometimes factors which promote bacterial infection. Excluding the pharynx and nose, bacterial colonisation of the respiratory tract is unusual and, if it occurs, it may be regarded as the first stage of an infection. Sometimes, it can be difficult to determine whether a given organism is a coloniser or an invader.

1. Pathogenic Organisms Viral infections rarely necessitate any specific therapeutic intervention and most measures available are directed against bacterial infection. The bacteria which cause the great majority of respiratory infections are Streptococcus pneumoniae (the pneumococcus) and Haemophilus influenzae. The specific treatment of respiratory infections is virtually synonymous therefore with attempting to eliminate these two organisms (table I). In children, it is quite likely that Streptococcus pyogenes is also a cause of infections, particularly in the upper respiratory tract, and this organism would be eliminated by any effective therapy directed against the other two bacterial pathogens.

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Table I. Respiratory Infections

Otitis media } Sinusitis Bronchitis Pneumonia

Almost all caused by pneumococcus and/or Haemophilus

1.1 Pneumococci Streptococcus pneumoniae, also called the pneumococcus and, in the USA, Diplococcus pneumoniae, is a capsulated organism. More than 40 different serological types of capsule can be differentiated.

1.1.1 Infections Caused by Pneumococci Organisms of the lower capsular types, principally types I , II , and III , are highly virulent and can cause lobar pneumonia and bacteraemia, as well as less spectacular infections . Pneumococci of higher capsular types are less virulent and tend to cause superficial infections such as rhinitis, sinusitis, otitis media, bronchitis and bronchopneumonia (which can be regarded as severe bronchitis with local alveolar extension). Blood cultures with these higher capsular types are usually negative. The prevalence of different pneumococcal serotypes varies from time to time and hence their involvement in respiratory infections . Pneumococci mainly cause acute infections and do not seem to persist for long in vivo.

1.1.2 Sensitivity to Antibiotics Pneumococci are uniformly resistant to aminoglycoside antibiotics such as streptomycin and gentamicin but sensitive to the penicillins, cephalosporins, co-trimoxazole (trimethoprim-sulphamethoxazole), lincomycin, clindamycin and chloramphenicol. Although they are also sensitive to the sulphonamides, these agents are seldom effective in eliminating pneumococcal infection (unless combined with trimethoprim) as they are inactivated by pus. In vitro tests usually show pneumococci to be sensitive to erythromycin but it is doubtful if sufficient tissue levels are achieved to eliminate this organism readily. Some 10% of strains now show resistance to tetracycline . Some strains are also now being reported as exhibiting partial resistance to penicillin G (benzylpenicillin) but not to ampicillin. This means that although large doses of penicillin G would be effective in eliminating them, penicillin V (phenoxymethylpenicillin) might not be (since pneumococci are less sensitive to it than penicillin G) and this is a worrying trend .

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1.2 Haemophilus influenzae Only 5% of Haemophi/us injluenzae strains are capsulated and these can be subdivided into 6 serotypes , A to F. 1.2.1 Infections Caused by H. injluenzae Of the capsulated strains, only type B shows great virulence and can cause pneumonia, septicaemia , meningitis, septic arthritis, epiglottitis etc . in young children aged I to 5 years. In older subjects however, they behave just like the non-capsulated strains which are superficial invaders only, causing infections like those of the higher pneumococcal capsular types with negative blood cultures. The incidence of respiratory infections with non-capsulated Haemophilus strains is fairly constant. Infection by these organisms can be acute or chronic, and frequently they may co-exist with pneumococci. In patients with pneumonia it is common to culture both Haemophi/us and pneumococcus from the sputum but only pneumococci from the blood . Of the two organisms, it has been estimated that the majority of respiratory infections are caused by Haemophi/us, although epidemics of pneumococcal infection are seen. Haemophilus parainjluenzae has slightly different cultural characteristics to H. injluenzae but is best regarded as being of similar pathogenicity. 1.2.2 Sensitivity to Antibiotics Haemophilus shows in vivo resistance to penicillin V and G, erythromycin, lincomycin, and clindamycin but is uniformly sensitive to ampicillin, streptomycin, tetracycline , chloramphenicol and co-trimoxazole. The position with regard to the cephalosporins is not yet completely clear.

1.3 Other Pathogens 1.3.1 Staphylococcus aureus This organism does not cause minor superficial infections of the lower respiratory tract but is believed to be involved in some cases of sinusitis. Occasionally Staph . aureus causes a severe form of pneumonia, its entry to the alveoli being facilitated in some way by the influenza virus. Staphylococcal pneumonia is in fact seen principally during influenza epidemics. The organism can also cause superficial infection in patients with chronic bronchial suppuration , particularly cystic fibrosis and , to a lesser extent, bronchiectasis.

Sensitivity to Antibiotics Staph. aureus is a potential penicillinase producer and should be regarded as resistant to penicillin G and V, as well as to ampicillin. It is generally sensitive to

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cephalosporins, methicillin, cloxacillin, lincomycin, the aminoglycosides, chloramphenicol and co-trimoxazole. Oral erythromycin is risky.

1.3.2 Freidlander 's Bacillus Of the enterobacteria, only some varieties of klebsiella can be regarded as being primarily pathogenic in the respiratory tract . The genus Klebsiella has over 70 capsular serotypes. Types I to 6, which are often grouped together as Friedlander's bacillus, are virulent to animals as well as being primary respiratory pathogens in man. Types 7 to 70, which are termed Kl. aerogenes, are bowel organisms and their presence in the respiratory tract is largely accidental and of similar significance to that of Esch. coli. Pneumonia due to klebsiellae is very rare, but can be caused by type I or 2 which are sometimes called KI. edwardsii and sometimes confusingly KI. pneumoniae. Type 4, KI. ozaenae, is the most common pathogen but it usually causes chronic secondary infection in bronchiectasis, cystic fibrosis and sinusitis. The whole picture is often confused because of the use of the terms KI. pneumoniae, Kl. aerogenes and Friedlander's bacillus interchangeably and indiscriminately to depict organisms with respiratory pathogenicity as different as that of Staph. aureus and Staph. albus. Sensitivity to Antibiotics Klebsiellae are sensitive only to aminoglycosides such as gentamicin and kanamycin as far as the respiratory tract is concerned.

1.3.3 Pseudomonas aeruginosa Pseudomonas aeruginosa is not a primary respiratory pathogen. However, in patients with chronic suppuration such as bronchiectasis and cystic fibrosis, it can assume a virulent so-called mucoid form which is very difficult to eradicate. Sensitivity to Antibiotics Gentamicin is the only really effective anti-pseudomonas agent in the respiratory tract, but even gentamicin has its many failures, particularly in the treatment of cystic fibrosis.

1.3.4 Other Gram Negative Bacilli Non-mucoid pseudomonas, Esch. coli, KI. aerogenes, Proteus spp. and other less common species of enterobacteria are normally non-pathogenic in the respiratory tract. However, they are resistant to most of the orally used antibiotics and can multiply in the pharynx and thence invade the lower respiratory passages. Consequently , they can be recovered from sputum cultures and the clinician may be tempted to prescribe medication for them , even though they

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are not primarily pathogenic . They can, however, elaborate penicillinase and other enzymes believed to be capable of destroying antibiotics, and thus interfere with therapy directed against the underlying pneumococci and Haemophilus . Sometimes in states of lowered resistance they can invade the alveoli and in turn the blood stream, as can other organisms oflow virulence. 1.3.5 Mycoplasma Mycoplasma pneumoniae which is an organism somewhere between a bacterium and a virus, can cause pneumonia . As it lacks a cell wall, it does not respond to cell-wall acting antibiotics such as penicillin but it is affected by tetracycline and erythromycin. 1.3.6 Fungi Primary fungal infection in healthy patients is rare. Various fungi are being reported in the lungs in an increasing number of patients on immunosuppressive therapy but such patients are uncommon outside large hospitals. Candida albicans is an antibacterial-resistant yeast which can colonise squamous surfaces such as those of the mouth and pharynx when its competition is removed by antibacterial therapy. Hence it is frequently reported in sputum cultures but should not be regarded as of any significance.

In general, Str. pneumoniae, H. influenzae, Staph. aureus, Friedlander 's bacillus and Ps. aeruginosa are called the potential respiratory pathogens as most respiratory infections are caused by these organisms and their presence in sputum may conceivably indicate that they are playing a role. Some organisms are definitely not pathogenic and these include Staph . albus, Str. viridans, nonhaemolytic streptococci, certain non-pathogenic corynebacteria termed diphtheroids, and Neisseriae such as N. catarrhalis and N. sicca.

2. Antibiotics Used in the Treatment of Respiratory Infections

2.1 Penicillin Benzylpenicillin or penicillin G is administered parenterally and is effective for the treatment of pneumococcal infection but not for Haemophilus. Phenoxymethylpenicillin or penicillin V is also of no value for Haemophilus and in addition may not be effective in some cases of pneumococcal infection. The same also applies for phenethicillin.

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2.2 Ampicillin and Related Compounds Ampicillin is of proven value in the treatment of both Haemophilus and pneumococcal infections of the respiratory tract. It is safe in children and pregnant women, but about 5% of persons given ampicillin develop a harmless toxic morbilliform rash which is dose-related and not an allergic phenomenon it can disappear even if the ampicillin is continued and does not necessarily recur on further administration. Such a rash is more frequent in patients with viral infections, particularly infectious mononucleosis. Related compounds include epicillin and pivampicillin, the latter being an ampicillin ester which releases ampicillin in the body . Little has been published about these agents to suggest that they are superior to ampicillin. Another related compound amoxycillin appears to have some advantages over ampicillin in being more active and therefore less likely to produce the toxic rash as lower doses can be given. Although any superiority over ampicillin in clinical practice has yet to be firmly established, some authorities feel that amoxycillin should be now used in preference to ampicillin when oral therapy is required. Unfortunately no parenteral form is as yet available. Although ampicillin and its related compounds are bactericidal in vitro, their capacity to eliminate organisms in vivo is dose-related and relapses often occur after apparently successful therapy because inadequate doses have been given.

2.3 The Tetracyclines The tetracyclines are bacteriostatic and their function therefore is to suppress bacterial growth while other immune mechanisms complete their destruction . A few Haemophilus strains and some 10% of pneumococci are resistant to the tetracyclines. As their action is bacteriostatic, patients with chronic disorders such as chronic bronchitis and bronchiectasis where local immunity is low, frequently relapse when therapy is discontinued. Divalent cations such as iron, calcium and magnesium (e.g. in antacids) impair the absorption of the tetracyclines. The absorption rate is not high and if oral doses of tetracycline beyond 250mg are given gastro-intestinal .side-effeets tend to occur, without any great increase in therapeutic effect. With the exception of doxycycline, the tetracyclines can cause a rise in blood urea, particularly in older subjects. They can also cause dental staining in children and therefore should be avoided if possible in children under the age of 8 and in pregnant or possibly pregnant women. Tetracycline hydrochloride is of proven value in respiratory infections, combination with an anti-candida agent such as nystatin does no harm but

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confers little real benefit. The longer-acting tetracyclines methacycline and minocycline are probably also effective but little published evidence attesting to their efficacy against Haemophilus is available. Moreover, neither are free of the urea elevation problem, and in addition, minocycline has a tendency to produce vertigo. These agents possess no significant advantages over tetracycline hydrochloride in the treatment of respiratory infections and there is little point in using them. Another long-acting tetracycline doxycycline has been shown to be effective in the treatment of bronchitis in some published trials. However, with increasing resistance to the tetracyclines developing it is probably wiser to prefer tetracycline hydrochloride 250mg 4 times per day to maximise tissue concen trations.

2.4 Co-Trimoxazole (Trimethoprim-Sulphamethoxazole) Sulphonamides alone are inactivated by thymidine in pus and therefore are of little value in treating respiratory infections. However, the combination of a sulphonamide plus trimethoprim is not affected in this way. Co-trimoxazole, a 5: I combination of sulphamethoxazole and trimethoprim, is bactericidal and effective against both Haemophilus and pneumococci. It appears to be safe for use in children but it may be unwise at this stage to use it in pregnant women. Co-trimoxazole can cause nausea in some patients but is well absorbed if taken with food .

2.5 Chloramphenicol This agent is very effective against both pneumococcal and Haemophilus infections, but its use should be restricted to only very seriously ill patients due to its bone marrow toxicity.

2.6 Erythromycin Although Haemophilus and pneumococci exhibit in vitro sensitivity to this antibiotic, clinical trials in bronchitis have been disappointing. In general, bronchial secretion levels of erythromycin are lower than the level needed to inhibit Haemophilus. The most widely used erythromycin form is erythromycin stearate and this is safe to use, although it may cause nausea in a few patients and occasionally skin rashes. Its absorption is unpredictable however, and it is not recommended for the treatment of respiratory infections. The same also applies for erythromycin estolate despite its better absorption.

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Treatment of Respiratory Infections Table II. Sensitivity of Haemophilus and pneumococcus to antibiotics Antibiotic

Pneumococcus

Haemophilus

Penicillin G Penicillin V Ampicillin/Amoxycillin Tetracycline Co-trimoxazole Lincomycin Erythromycin

S S or R S S, some R S S

R

R

R

S' S' S' R R

S = Sensitive R = Resistant 1 Antibiotic useful

2.7 Cephalosporins These antibiotics are less effective than ampicillin in the treatment of respiratory infections. Cephalothin has little effect against Haemophilus although it is perfectly adequate for treating pneumococcal infections. Cephaloridine is very effective against both common respiratory pathogens but needs to be given by injection and is nephrotoxic in a dose of 6g per day or higher. Cephalexin is active orally and is useful in infections in other parts of the body in patients who are allergic to penicillin and who would have otherwise been given ampicillin. However, its efficacy against Haemophilus infections is dubious . 2.8 Penicillin and Streptomycin Combination This combination is time-honoured in the prophylaxis of post-operative surgical infections . Penicillin is effective against pneumococci and streptomycin against Haemophilus. However, it seems wiser practice now to use ampicillin instead . 2.9 Lincomycin and Clindamycin These antibiotics are effective against pneumococci but not Haemophilus . Some 10% of patients experience severe diarrhoea and in a few cases an acute colitis may develop. Consequently they should be used with caution . There is therefore a limited armamentarium for the satisfactory treatment of respiratory infections. Sensitivity of the common pathogens to antibiotics is summarised in table II where it can be seen that only 3 agents.namely ampicillin

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(or amoxycillin), tetracycline and co-trimoxazole, are safe and effective for the treatment of such infections .

3. Sputum Cultures Haemophilus and pneumococci are often overlooked on culturing due to technical difficulties in their isolation. Even if one of these organisms is reported, the other may still be there, and it is always best to assume that both are present in any respiratory infection, upper or lower.

4. Antibiotic Sensitivity Tests

In general, the tissue concentration of antibiotics in pneumonia is similar to that in the blood stream . However, in the bronchi the concentration of antibiotics achieved is only about 1/10 that of the serum level. There is no agreed standard battery of antibiotic disc strengths used in the assessment of antibiotic sensitivity of Haemophilus or pneumococcus if they are isolated. In fact, many of the discs used contain concentrations of antibiotics that are too high to truly represent sensitivity or resistance and, in the case of bronchial infections, reports of sensitivity (e.g. to penicillin) can be misleading. Again, for technical reasons, estimation of the sensitivity of these organisms to co-trimoxazole can be difficult and reports of resistance to this combination are seen with organisms which are really sensitive. Hence, the laboratory can be of limited value in the assessment of respiratory infections, particularly bronchial ones. It can be often regarded as wise practice to treat patients with simple infections empirically with either ampicillin (or amoxycillin) , tetracycline or co-trimoxazole without recourse to cultures , and only use cultures if the expected response to therapy does not occur . In pneumonia, the situation is different as will be discussed below.

5. Principles ofManagement

The principles of management are summarised in table III. 5.1 Pneumonia Most instances of pneumonia are due to pneumococci and it is a wise general rule that one should choose an antibiotic effective against pneumococci in treatment despite sputum culture reports.

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Table II!. Principles of therapy for respiratory infections 1.

Pneumonia a) Admit to hospital b) Confirm by x-ray c) Blood and sputum cultures important d) Assume pneumococcal e) Ampicillin treatment of choice

2.

Bronchitis and Sinusitis a) Pus in sputum b) Assume Haemophilus and pneumococci present c) Cultures not important d) Treat with ampicillin (or amoxycillin) , tetracycline or co-trimoxazole

5.1.1 Diagnosis Pneumonia is an acute infection and it is best to arrange for a chest x-ray to confirm the presence of pneumonia since a clear chest x-ray excludes it . The main problem in differential diagnosis of lobar pneumonia is pulmonary infarction . Patients with sub-acute infections and radiological opacities should be investigated for the possibility of carcinoma or tuberculosis. Patients with suspected lobar or segmental pneumonia should be admitted to hospital. There are many reasons for this: 1) Sick patients may not absorb medication orally and therefore in hospital round-the-clock parenteral therapy can be used 2) Pulmonary scans can be carried out if necessary 3) Sputum and blood cultures can be rapidly processed and further cultures done if there is an initial failure to respond to treatment 4) Blood gas measurements can be made in sick patients 5) Physiotherapy can be performed if necessary 6) Measures can be taken if complications occur. In general, patients should have sputum and blood cultures. Often the causal organism is recovered from the blood rather than from sputum . It is important to attempt to find the organism because staphylococci and other organisms can cause pneumonia, whereas they do not cause bronchitis. If such organisms are present, then the basic treatment will need to be drastically altered.

5.1.2 Treatment Analgesia may be required and in patients with normal blood gases, narcotics can be quite safe. Patients with upper lobe opacification do not need physiotherapy unless they have accompanying bronchitis . Lower lobe consolidation on the other hand may be due to severe bronchitis with inspissation of

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secretions producing a collapsed lobe, and in such cases physiotherapy will be necessary and maybe a bronchoscopy. A penicillin type of agent parenterally is necessary until the temperature has subsided. This will occur in some 24 to 72 hours. Traditionally, soluble penicillin G 500,000 to 1,000,000 units is given 4 times daily. A problem arises on day 2 or 3 when the patient improves sufficiently for a change to oral medication to be made. Penicillin V is not as potent as penicillin G and some patients may not respond to it. Moreover, an associated Haemophi/us infection will not respond to penicillin V, and it may therefore be wiser to use ampicillin (or amoxycillin) orally at this stage. In fact it may be best to use ampicillin from the start parenterally and then change to oral therapy as necessary. This will suppress or eliminate both potential pathogenic organisms. The parenteral dose of ampicillin should be limited to 500mg as higher doses may tend to cause a toxic rash. The adult dose of ampicillin orally is 500mg 4 times daily at least and this should be continued until clinical signs of inflammation have disappeared . This means I to 2 weeks of treatment. The radiological resolution may lag behind clinical recovery. Complications such as pleural effusion and empyema are usually seen in patients given oral therapy at the beginning, particularly with tetracycline. However, if oral therapy alone is contemplated then ampicillin or co-trimoxazole may be quite adequate. As 10% of strains of pneumococci are now resistant to tetracycline, this should not be regarded as first choice therapy. Erythromycin, lincomycin and clindamycin are also not recommended. If there is a history of penicillin allergy (i.e. a history of an urticarial rather than a morbilliform rash), then cephalothin may be given, followed by cephalexin at a later stage. 5.1.3 Pneumonia Due to Other Organisms If the patient fails to respond to this treatment, then the infection is not pneumococcal . Pulmonary infarction will need to be excluded and culture results will need to be looked at to determine if staphylococci have been isolated. Klebsiella pneumonia is very rare, usually occurring in older subjects accompanied by localised cavitation , high fever and delirium. The organism will be found on blood culture and will always be found in the sputum . Failure to respond to an antibiotic cover directed against pneumococci, staphylococci and Gram-negative bacilli means that the diagnosis is likely to be viral or mycoplasma infection. At this stage, tetracycline may be used with general supportive therapy .

5.2 Bronchopneumonia This will be seen in a sick patient with possibly a past history of chronic bronchitis or who is debilitated. Widespread physical and radiological signs are

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evident. In general, the cause of the infection will be pneumococcus plus Haemoph i/us but this type of patient may also have a Gram-negative infection.

Staphylococcal pneumonia usually produces large areas of radiological opacification and occurs principally during influenza epidemics. In patients with bronchopneumonia there is a high mortality and it is important for such persons to be admitted to hospital . Blood gas measurements will be necessary and it is important that there are facilities available for the management of acute exacerbations of chronic bronchitis such as IPPR with bronchodilators, physiotherapy, intubation, etc. 5.2.1 Treatment Ampicillin is the basic antibiotic which should be used and if the patient is very ill then gentamicin and cephalothin or methicillin can be added . In this type of patient it is important not to overlook sputum and blood cultures at the outset.

5.3 Bronchial Infections In general, the presence of pus in the sputum is an indication that bronchial rather than alveolar infection is present. The organisms are usually H. injluenzae or pneumococci , or both. 5.3.1 Acute Infections In acute infections ampicillin (or amoxycillin), co-trimoxazole or tetracycline should be used. The dose should be adequate - i.e. in adults 500mg ampicillin 4 times daily, 250mg tetracycline 4 times daily or two tablets of co-trimoxazole twice daily. Sputum cultures are not as important as in pneumonia because the organisms are less likely to be found . Blood cultures are negative and often there is no pyrexia ; the chest x-ray is clear. Treatment with the antibiotics should be continued until all signs of acute infection have disappeared . It is unwise to use erythromycin or penicillin V. Acute bronchitis is usually initially viral in origin and the development of bacterial infection is shown by the presence of pus in sputum . Many patients with attacks of acute asthma may also have this viral-bacterial trigger. The administration of bronchodilators, cough mixtures or cough suppressants depends on the severity of symptoms. Probably most patients with acute bronchitis have minor symptoms and need no specific treatment at all. When therapy is felt to be necessary there is little point in giving antibiotics before sputum purulence develops, except in patients with a prior history of acute attacks of bronchitis or asthma causing considerable discomfort. However, if a definite bacterial infection is present and treatment is thought to be worthwhile ,

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it is preferable to treat the cause with antibiotics rather than use cough mixtures or cough suppressants alone. There is little more than placebo value in traditional cough mixtures. 5.3.2 Acute Exacerbations of Chronic Infections In the event of an acute infection occurring on a chronic bronchitis background, the same organisms are likely to be present and the same antibiotics can be used. However, relapses after apparently successful therapy are quite frequent and it may be necessary to continue antibiotic treatment for weeks or months. Ultimate cessation of therapy usually can be determined by the patient's failing to remember to obtain more prescriptions and discovering in this way that the infection has been eliminated. 5.3.3 Chronic Infections In chronic pulmonary suppuration such as cystic fibrosis or bronchiectasis, treatment is usually effective if it is directed against Haemophilus influenzae, since pneumococci usually do not cause chronic infection. In these patients, however, pseudomonas and Friedlander's bacillus may be a problem and if this is likely it is best for the patient to be referred to a consultant as treatment of these infections is particularly difficult. The use of oral medication for the treatment of Pseudomonas or Klebsiella infections is to be deprecated, because it is not effective.

5.4 Sinusitis Here again the organisms which cause infection are usually Haemophilus and/or pneumococcus . Treatment with ampicillin (or amoxycillin), cotrimoxazole or tetracycline is usually effective whereas treatment with erythromycin or penicillin V is not. In general, the duration of therapy for sinusitis needs to be longer than for bronchitis as it seems to take longer for the antibiotics to penetrate into the secretions. It is important in patients with sinusitis for adequate analgesia to be given and steam inhalation may help drain the secretions. It is important also to look for underlying allergic rhinitis or nasal polyposis which might be predisposing to the sinusitis. Long-term antibiotic therapy may also be necessary.

5.5 Otitis Media It has been shown that Haemophilus and pneumococcus are the main causes of bacterial infection in otitis media. However, erythematous drums may also be

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caused by allergic reactions and viral infections. Analgesics are important and, in general, either ampicillin or amoxycillin is the treatment of choice since most otitis media occurs in children and in young children at least Haemophilus infection is more common. 5.6 Failure to Respond to Treatment Generally, superficial purulent respiratory infections of the upper or lower respiratory tract respond well to ampicillin, co-trimoxazole or tetracycline . Failure to respond may mean that the pneumococcus or Haemophilus strain is resistant to the agent used, although this is uncommon . Under these circumstances one should switch to another of the three agents, and if this is not effective then sputum or sinus fluid culture will be necessary. If a heavy growth of coliform bacilli or Pseudomonas is forthcoming then it may be assumed that these organisms are destroying the antibiotics administered. In the case of coliform bacilli, co-trimoxazole may be worth trying (if it has not already been used) because they often respond together with the underlying pathogen, although Friedlander's bacillus does not. If the infection does not respond to co-trimoxazole or if Pseudomonas is present, then a decision must be made. Either therapy should be suspended, in which case the Gram-negative bacillus may, in time, disappear spontaneously, or if the patient's condition does not justify this, then topical gentamicin therapy is advised. Gentamicin by injection does not satisfactorily eliminate coliform bacilli or Pseudomonas from the bronchi or sinuses, but if administered by inhalation, it does suppress them and allow the other antibiotics to eliminate the underlying pathogens. Gentamicin is best given in this way in hospital, either as an in-patient or as an out-patient, using a Bird or Bennett respirator. A dose of 20 to 60mg is used without dilution depending on the ability of the patient to tolerate the therapy . A 60mg dose requires more breaths than 40 or 20mg. This treatment is administered 3 times daily for a few days by using a mask if there is a nasal or sinus infection. When gentamicin is administered in this way, serum level monitoring is not necessary as no significant systemic absorption takes place.

Author's address: Dr M.W. Bums, 229 Macquarie Street, Sydney, NSW 2000 (Australia).

Treatment of respiratory infections.

Drugs 10: 437-450 (1975) Treatment of Respiratory Infections M.W. Bums St. Vincent's Hospital, Sydney A respiratory infection can be said to be pres...
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