Pneumonia, therapy

Pneumonia is predominantly a serious clinical picture. Treatment is only possible on an outpatient basis in the case of mild forms of the disease. All other patients should - at least initially - be treated as inpatients. Inpatient treatment is also indicated in cases of uncertain home care.

Diagnostic measures should not delay the start of therapy. Therefore, after removal of bronchial secretions and blood cultures (positive in 30-50 %!), an immediate treatment is recommended. This must be adjusted after receipt of the antibiogram.

Pneumonia is the most common infectious disease leading to death in industrialized countries. Worldwide, it ranks fourth in the statistics on causes of death.

see also acuteinterstitial pneumonia; cryptogenicallyorganizing pneumonia; desquamative interstitial pneumonia; LIP; RB-ILD; NSIP; IPF / UIP; atypical pneumonia; pneumocystis pneumonia; cheesy pneumonia; pneumococcal pneumonia; pneumonia;

An exception to the usual therapeutic measures is made for patients with severe concomitant diseases and a poor prognosis. In these patients, pneumonia often occurs additionally in the terminal phase. Here, the therapeutic goal should be based exclusively on symptomatic therapy, such as oxygen, non-invasive ventilation, morphines, and the preservation of patient autonomy (as far as possible). Anti-infectives are deliberately avoided at this stage - usually after consultation with the relatives - in order not to prolong the dying process.

Therapy for outpatients

1. For patients without concomitant diseases, who have not received antibiosis within the last 3 months, aminopenicillin e.g. amoxicillin 3x1g/d p.o. is the drug of choice. Alternatives would be macrolides such as azithromycin 1x500 mg/d p.o. on day 1, followed by 250 mg/d p.o. (10% of pneumococci, however, are resistant to macrolides) or tetracycline such as doxycycline 2x100 mg/d p.o.

2. Patients with concomitant diseases, residents of nursing homes or previous antibiosis in the last 3 months: Betalactam as the drug of choice e.g. amoxicillin/clavulanic acid 2 -3x1g/d p.o. or as an alternative fluoroquinolone of the group 3 / 4 e.g. Levofloxacin 1-2x500 mg/d p.o..

Therapy for in-patients

Patients without the risk of Pseudomonas aeruginosa infection should receive amoxicillin/clavulanic acid 3-4x2.2 g/d plus macrolide e.g. azithromycin 1x500 mg/d.

Patients with the risk of a Pseudomonas aeruginosa infection should receive a Pseudomonas effective penicillin plus beta-lactamase inhibitor piperacillin/tazobactam 3-4x4.5g plus fluoroquinolone e.g. levofloxacin 1-2x500mg/d.

In in-patients the antibiosis is usually given intravenously, with the exception of fluoroquinolones. The duration of therapy is about 5 - 7 days.

Special therapies for individual forms of pneumonia:

Therapy for interstitial pneumonia:

Acute interstitial pneumonia (AIP): In rare cases of acute interstitial pneumonia , which is associated with a high mortality rate (>60%), purely supportive measures are indicated, as there is no reliable treatment with medication. Intensive medical care is obligatory. Often patients are already ventilated at the time of diagnosis. Non-invasive ventilation is primarily recommended here, as otherwise the high ventilation pressure and the high inspiratory oxygen concentration will probably accelerate the disease. After exclusion of all important differential diagnoses, an attempt should be made to treat the disease with high-dose steroids, although a reliable therapy has not yet been found:

- 2 x 500 mg prednisolonefor 5 days

- then 1 x 500 mg for 3 days

- then 1 x 250 mg for 3 days

The further procedure should then be decided on the basis of the course of events. As a precaution, the simultaneous administration of an antimycotic is recommended under high-dose immunosuppression:

e.g. Fluconazoleand an additional antibiosis, primarily a second generation cephalosporin

z. e.g. cefuroxime 3 x 1,5 g/d i.v. plus macrolide

e.g. erythromycin 3 - 4 x 1 g/d i.v.

Cryptogenically organized pneumonia (COP): 2/3 of the patients undergo clinical recovery under glucocorticoids. However, it is also possible that the disease - despite the glucocorticoids - takes a rapidly progressive fatal course.

Prednisolone: Both the optimal dosage and the duration of treatment are not known in interstitial lung diseases. The following schemes can be found in the literature:

Initial dose 0.5 - 1 mg/kg bw/day orally, but not more than 50 mg/d. This treatment should be carried out for 4-12 weeks and the patient should then be re-examined in detail.

Initial dose 1 mg/kg bw/day, but not more than 50 mg/d. After 4 weeks halve the dose, after another 4 weeks halve it again and examine the patient in detail.

Desquamative interstitial pneumonia (DIP): The most important measure here is to stop nicotine consumption. This alone makes spontaneous remissions possible. If no remission can be achieved under nicotine withdrawal or if the symptoms are initially very pronounced, treatment with glucocorticoids should be carried out.

Prednisolone: Initial dose 1 mg/kg bw/d, but not more than 50 mg/d. After 4 weeks halve the dose, after another 4 weeks halve it again.

Lymphocytic interstitial pneumonia (LIP): Due to the rarity of the disease there are no clear therapy recommendations. Essentially, the underlying disease should be treated. A successful treatment with glucocorticoids or immunosuppressive drugs should be tried if necessary.

Prednisolone: Both the optimal dosage and the duration of treatment are not known in interstitial lung diseases. The following schemes can be found in the literature:

Initial dose 0.5 - 1 mg/kg bw/d orally, but not more than 50 mg/d. This treatment should be carried out for 4-12 weeks and the patient should then be re-examined in detail.

Initial dose 1 mg/kg bw/d, but not more than 50 mg/d. After 4 weeks halve the dose, after another 4 weeks halve it again and examine the patient in detail.

Azathioprine: 2 mg/kg bw/d, but not more than 150 mg/d. The dose should be increased in 50 mg steps weekly until the target dose is reached. Note: In case of intolerable side effects of corticosteroids or in elderly patients, prednisolone can be combined with 3 x 600 mg ACC or used as sole therapy, following the IFIGENIA study. The course of the disease does not seem to be negatively affected by this (the chronic inflammation underlying fibrosis probably reacts positively to the reduction of antioxidants). As a rule, practically all changes in the lung are reversible under treatment - apart from cysts. Note: Cysts may develop from alveolar consolidation.

Respiratory bronchiolitis with interstitial lung disease (RB-ILD):

Significant improvement of the disease by nicotine withdrawal alone, even with pronounced interstitial changes. Treatment with corticoids is usually not necessary.

Non-specific interstitial pneumonia (NSIP):

Patients with NSIP should always be treated as the disease responds well to medication. Occasionally, there are reports of patients remaining stable for years under treatment. Even complete remissions are possible under the therapy. If fibrotic changes dominate, the therapeutic effect is similar to that of idiopathic pulmonary fibrosis with the picture of usually interstitial pneumonia (IPF/UIP) (drug therapy has only a limited effect; early listing for transplantation is required). Therapeutic procedure for NSIP:

Initially, monotherapy with prednisone should be given. Azathioprine is only given additionally in case of insufficient effect or in the further course to reduce the toxicity of cortisone.

Prednisolone: Initial dose 1 mg/kg bw/d, but not more than 50 mg/d. After 4 weeks the dose is halved, after another 4 weeks it is halved again.

Azathioprine: 2 mg/kg bw/d, but not more than 150 mg/d. The dose should be increased in 50 mg steps weekly until the target dose is reached.

In case of intolerable side effects of corticosteroids or in elderly patients, prednisolone can be combined with 3 x 600 mg ACC or used as sole therapy - following the IFIGENIA study. The course of the disease does not seem to be negatively affected by this (the chronic inflammation underlying fibrosis probably reacts positively to the reduction of antioxidants).

Idiopathic pulmonary fibrosis with the picture of a usually interstitial pneumonia (IPF /UIP):

Currently, no therapy is known that could prolong survival. The most important measure is therefore the rapid detection of the disease and listing for lung transplantation.

Listing should be done at the latest when the disease is progressive both clinically and based on lung function. This is the case if, within a period of 3 months:

vital capacity and total lung capacity decrease by >10

DLCO falls by >15

Oxygen saturation drops > as 4

Note: Previously, therapies were performed with a combination of prednisolone and azathioprine or cyclophosphamide. However, it has now been shown that these therapeutic measures have no clear effect on the disease process. According to the IFIGENIA study, only the combination of prednisolone, azathioprine plus an additional 3 x 600 mg ACC showed a slower deterioration of VC and DLCO. It is therefore recommended to try this medication in patients < 70 years of age and without contraindications.

Prednisolone: Initial dose 1 mg/kg bw/d, but not more than 50 mg/d. After 4 weeks halve the dose, after another 4 weeks halve it again. After another 4 weeks the further procedure should be decided individually.

Azathioprine: 2 mg/kg bw/d, but not more than 150 mg/d. The dose should be increased in 50 mg steps weekly until the target dose is reached.

ACC: 3 x 600 mg/d. In case of intolerable side effects among glucocorticoids and in elderly people ACC may be prescribed as the sole medication. A worsening of the course of the disease was not observed among them.

Oxygenation: In hypoxemia the patient should receive oxygen, but only up to a dose at which the shortness of breath has subjectively improved. There is evidence that high oxygen delivery via radical formation accelerates the progression of pulmonary fibrosis.

Morphines: If massive dyspnea at rest occurs in the final stage, morphines in higher doses should be used additionally for symptomatic treatment.

Ventilation: Hypercapnia occurs relatively late in patients with IPF as opposed to those with COPD. In cases where hypercapnia is observed early, COPD has usually already existed before.

In this clinical picture, the ventilation of the patients is a purely palliative measure, the only exception being bridging measures until transplantation. In any case, a form of non-invasive ventilation should be chosen. Invasive ventilation would require ventilation at a very high frequency and with a low volume, as the lung has considerable stiffness and volume reduction at this stage. The only exception to invasive ventilation could be infection-related exacerbation in an otherwise early stage of IPF.

Therapy of atypical pneumonia: Depending on the pathogen, it may be effective:

- tetracyclines; are effective against mycoplasma, chlamydia, Coxiella burnetii, etc. (e.g. doxycycline 2x100 mg/d p.o.)

- Macrolides; are effective against Haemophilus, Mycoplasma, Chlamydia, Legionella and others (e.g. Azithromycin 1x1 g i.v., then reduction to 1x500 mg/d)

- Fluoroquinolones; are effective against pneumococci, Haemophilus influenzae, Legionella, mycoplasma, Chlamydia, etc. ( e.g. Levofloxacin 2 x 500 mg/d)

The highest mortality rate of atypical pneumonia is found in the disease caused by legionella (fluoroquinolones effective; e.g. levofloxacin in maximum dose, see above). It is - even with adequate therapy - about 10% and rises to > 50% in immunocompromised or pre-existing cardiovascular diseases. The mortality rate of the other pathogens is significantly lower. In the case of a severe clinical picture and the justified suspicion of atypical pathogens, dual therapy should be started immediately, as the diagnosis is sometimes time-consuming. After receipt of the pathogen proof, modification of the antibiosis.

Therapy of cheesy pneumonia:

If tuberculous genesis has been proven, there is an indication for antituberculous therapy. If a pleural effusion exists, initial pleural drainage is recommended to prevent rind formation. The drug treatment of cheesy pneumonia corresponds to the treatment of pulmonary tuberculosis and is always carried out with a combination of drugs. For this purpose, there are 4 main substances available as 1st choice agents: isoniazid, rifampicin, pyrazinamide and ethambutol. 2nd choice agent is recently - according to the WHO - streptomycin, as it cannot be administered orally and is no longer used in several countries for the treatment of uncomplicated tuberculosis.

The following dosage is recommended for daily administration:

Isoniazid (INH) 5 mg/kg KW, max. 300 mg

Rifampicin (RMP) 10 mg/kg KW, max 600 mg

Pyrazinamide (PZA) 25 mg/kg KW, max 2500 mg

Ethambutol (EMB)15 mg/kg KW, max. 1600 mg

A standard short therapy for adults is a 6-month chemotherapy. In the first 2 months, the so-called initial phase, a combination of INH, RMP, PZA and EMB is treated. In the following 4-month stabilization phase, treatment is continued with a combination of INH and RMP. The drugs should be administered orally 1 x / day as a single dose. In some countries, intermittent drug administration with 3 x weekly intake is practised during the stabilisation phase. This procedure is not recommended in Germany, as the maximum therapeutic safety is only given if the drugs are taken daily. If there are any doubts about the regular intake of the drugs, the intake must be constantly monitored. The success of the therapy should be checked regularly once a month, including the organs that are at risk from taking the medication. These include:

Liver function with INH, RMP, PZA (additive effect!)

ophthalmological controls in case of EMB

Renal function with aminoglycosides

Check audiogram for aminoglycosides

Blood glucose monitoring with additional administration of cortisone (see above)

Regular control of the patient's body weight.

Note: In >80 % of patients negative cultures are expected after 2 months of combination therapy.

Therapy of Pneumocystis Pneumonia:

Without treatment PCP is always fatal.

The drug of choice is trimethoprim-sulfamethoxazole(Cotrimoxazole). In mild to moderate cases, oral administration is possible (PaO2> 70 mmHg or PA O2 - Pa O2< 35 mmHg under ambient air). Patients with PaO2 < 60 mmHg in ambient air should receive intravenous therapy.TMP 5 mg/kg plus SMX 25 mg/kg every 6-8 hours p.o. (corresponds to 2-3 x 2 tablets of Cotrimoxazol forte per day) or as i.v. administration. Side effects: fever, hyperkalemia, cytopenia, exanthema, hepatitis

TMP plus dapsone: 5mg/kg every 6-8 hours p.o. plus dapsone 100 mg/d p.o. Side effects: haemolysis (in G6PD deficiency), methaemoglobinaemia, fever, gastrointestinal disorders, exanthema

Atovaquon: 2x750 mg/d p.o. Side effects: fever, exanthema. Hepatitis

Clindamycin plus primaquine: 300-450 mg every 6 hours p.o. or 600 mg every 6-8 h i.v. plus primaquine 15-30 mg/d p.o. Primaquine is not approved in Germany and is only available through the International Pharmacy. Side effects: Haemolysis (with G6PD), methaemoglobinaemia, exanthema, neutropenia

• Pentamidine: 3-4 mg/kg/d i.v. Side effects: hypotension, azoteemia, arrhythmias, pancreatitis, hypocalcaemia, neutropenia, hepatitis, blood sugar regulation disorders (life-threatening hypoglycaemia may occur days or weeks after the initial infusion!)

Accompanying medication:

Prednisone 2 x 40 mg/d for 5 days, then 1 x 40 mg/d for 5 days, then 1 x 20 mg/d for 11 days p.o. or i.v. (see also below).

Remark: In patients with HIV infection the therapy is only effective after > 4-5 days. The duration of therapy should be 21 days. Here, a temporary deterioration of the respiratory function often occurs shortly after the start of therapy. With simultaneous administration of glucocorticoids, this complication can be prevented - at least in HIV-infected patients with moderate to severe PCP. In mild PCP and non-HIV-infected patients, the benefit of cortisone has not yet been clarified. In patients without HIV infection we find a faster response to therapy (< 4-5 days). Here a therapy duration of 14 days is sufficient.

Therapy of pneumococcal pneumonia

Pneumococci are sensitive to penicillin. However, resistances occur more and more frequently, which vary greatly from region to region. The USA has the highest rate of resistance with > 50 %, in Spain, Hungary and France it is up to 50 % and in Germany < 10 % and is therefore negligible. The means of choice is:

Amoxicillin (3x1 g/d p.o.)

In case of known penicillin allergy

fluoroquinolone(moxifloxacin 1x400 mg/d or levofloxacin 1x500-750 mg/d), with moxifloxacin being more effective.

Clindamycin 600-1200 mg/d p.o. in single doses every 6 hours (90% effective) or azithromycin 1x500 mg/d p.o., then 250-500 mg/d p.o.) and clarithromycin 1x500-750 mg/d p.o. (both 80 % effective) are subordinate alternatives.

For patients with previous lung diseases (severe COPD, bronchiectasis etc.), betalactam is recommended as the drug of choice, e.g.

Amoxicillin/Clavulanic acid 2x2g/d p.o.

alternatively fluoroquinolone e.g. Levofloxacin 1x750 mg/d p.o..

Therapy for in-patients

Patients should receive amoxicillin/clavulanic acid 3-4x2.2 g/d plus macrolide e.g. azithromycin 1x500 mg/d.

Patients with the risk of an additional Pseudomonas aeruginosa infection should receive a pseudomonas effective penicillin plus beta-lactamase inhibitor piperacillin/tazobactam 3-4x4.5g plus fluoroquinolone e.g. levofloxacin 1-2x500mg/d

Therapy for in-patients in intensive care units:

betalactam e.g. cefotaxime 1-2 g i.v. every 8 h, ceftriaxone 1x2 g/d i.v. or ampicillin/sulbactam 2g i.v. every 8 h

PLUS

Macrolide e.g. or fluoroquinolone such as moxifloxacin 1x400 mg/d i.v.

In inpatients the antibiotic is usually given intravenously, with the exception of fluoroquinolones.

The duration of therapy varies, as the optimal duration of treatment is not known. Most recommendations speak of continuing the antibiosis for at least 3-5 days after defibrillation.

Therapy of pneumonia with immunosuppression:

Patients with congenital or acquired immune deficiencies, with therapies using biologicals, neutropenia under chemotherapy, organ transplantation or asplenia etc. can be affected by immunosuppression.

A broad potential spectrum of pathogens including fungi, opportunistic pathogens, etc. can be considered.

A careful diagnosis and, if necessary, an early consultation with infectiologists is recommended.

As far as general measures are concerned, the following should be carried out on patients, where necessary:

• physical rest
• adequate fluid intake (important in case of fever and for secretolysis)
• if necessary, heparinisation (enoxaparin sodium e.g. Clexane; dosage: body weight divided by 100 rounded = ml Clexane; e.g. 45 - 64 kg = 60 mg ready-to-use syringe or 65 - 84 kg = 80 mg ready-to-use syringe). The injection is made 1x/Tg subcutaneously.
• antithrombosis stockings if necessary
• NaCl inhalations
• in case of hypoxia oxygen by nasal probe
• Early mobilization after clinical improvement

The prognosis of pneumonia is - besides the pathogen - mainly unfavourably influenced by the following factors:

• Age of the patient (from the age of 30, mortality per decade of life increases by 2-3%)
• pre-existing illnesses, especially heart and lung diseases, diabetes mellitus, alcohol abuse, etc.
• congenital or acquired immune defects
• nosocomial pneumonia (has a lethality rate of > 20% and is therefore the most common fatal hospital infection)

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