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 MERKACIN IN TREATMENT OF SEVERE COMMUNITY-ACQUIRED PNEUMONIAS 
TAMAZ MAGLAKELIDZE, Doctor of Medicine, Professor
Georgian Respiratory Association, President.
 
Pneumonia is one of the widespread disorders and in the developed countries it takes fourth /fifth place in mortality rates. Despite wide array of antimicrobial medications lethal causes are still high. According to the published data pneumonias have general mortality rates of 11.8%, but it is highly variable depending on the causative agent. The highest mortality rates have those pneumonias which are caused by blue-green rods (Pseudomonads) 61.11%, Klebsiella (35.7%), Staphilococcus aureus (31.8%), mixed bacterial flora (23.6%). The lower mortality rates have those pneumonias, that are caused by Legionella spp (14.7%), Pneumococci (12.3%), Chlamidiae (9.8%), Hemophilus (7.4%), and Mycoplasma (1.4%). Etiologic classification of pneumonias on which international statistical classification is based is principally most appropriate but it is worth mentioning that in XXI century etiologic identification of pneumonias during the first patient encounter is impossible. That’s why highly pragmatic classification of pneumonias as Community-acquired and nosocomial or hospital acquired pneumonias is widely used. Such general classification is acceptable for only one practical use when choosing first-line antibacterial medications according to the causative agent of pneumonia. During history taking this classification aids physician in determining probable cause of pneumonia and contributes to be more selective and specific in choosing right antibacterial medication.
 
Community-acquired pneumonias are generally caused by: Streptococcus pneumoniae (Pneumococci), other Streptococci and Haemophilus. Pneumonias caused by Mycoplasma, Chlamidiae, Legionella spp. and Pneumocystis have increased during last periods. In youngsters pneumonia usually has single causative agent but in people older than 60 years it is mixed bacterial, from which ¾ is gram positive and gram negative flora. People in geriatric buildings and just discharged outpatients are at increased risk of developing pneumonias caused by Staphilococci and gram negative rods. Klebsiella is common cause of aspiration pneumonia in alcoholics.
 
In various publications about treatment methods of pneumonia, the most attention is paid at antimicrobial therapy. This is crucial because it is the correct antimicrobial therapy that determines the course and the result of pneumonia. On the other hand the sole target of antimicrobial therapy is inflammation suppression and eradication of the causative agent. Complete treatment of pneumonia should be etiologic and pathogenetic too, because the initial phase of the disease process is accompanied by deranged immune (inflammatory) functions.
 
Community-acquired pneumonias can be divided in to the three groups:
1. Pneumonias, that don’t require hospitalization.
2. Pneumonias, that require hospitalization.
3. Pneumonias, that require hospitalization and management in intensive care unit (ICU).
 
Pneumonias not requiring inpatient care are most numerous and comprise 80% of all pneumonias. The patients have mild forms of pneumonia, treatment is outpatient and mortality doesn’t exceed 1%.
 
Pneumonias, requiring inpatient care comprise 20%, such patients often have other chronic co-morbidities and have marked clinical symptoms, mortality rate approximates 10%.
 
The main criteria for hospitalization of the patients with community-acquired pneumonia are:
·    Age>70 years
·    Presence of various chronic disorders causing disabilities, such as: chronic obstructive pulmonary disease, congestive heart disease, chronic renal and liver insufficiency, diabetes, alcoholism or intravenous drug abuse, immunodeficiency states including AIDS.
·    Ineffective 3 days course of antibacterial treatment.
·    Altered level of consciousness
·    Probability of aspiration
·    Respiratory rate >30 min
·    Unstable hemodynamic parameters
·    Sepsis or disseminated infection
·    Inclusion of other viable lobes of the lung in the disease process
·    Significant pleural effusion
·    Cavity formation
·    Leucopenia (<4000 cells/ml) or marked leukocytosis (>20000)
·    Anemia (Hb < 90g/L)
·    Acute renal failure (blood urea nitrogen (BUN) >7mmol/L)
·    Lower social economic status
·    Criteria for placing patients with community-acquired pneumonias, in intensive care units (ICU) are:
·    Acute respiratory insufficiency: Hypoxemia (PaO2/FiO2<250 mmHg or <200 mmHg in chronic obstructive pulmonary disease), signs of diaphragmatic fatigue, need for mechanical ventilation.
·    Unstable hemodynamic parameters, shock (systolic pressure <90 mmHg or diastolic pressure <60 mmHg); need of vasopressors for more than 4 hours, urine output <20 ml/h (without hypovolemia).
·    Acute renal failure requiring dialysis
·    Acute thrombohemorrhagic syndrome, disseminated intravascular coagulation ( DIC)
·    Meningitis
·    Coma.
 
Patients who meet these criteria are considered having severe form of community-acquired pneumonia and are requiring management in intensive care unit.
 
Severe forms of pneumonias take significant place in overall pneumonias because they require qualitatively different diagnostic and treatment managements. Severe forms are frequently associated with bacteremia, special attention is paied at such agents as are Legionella spp., gram negative organisms including Pseudomonas aeruginosa. Mortality rates in such cases can attain 25-50%.
 
These last years antibacterial resistance of the organisms causing pneumonias has been increasing. Pneumonias caused by penicillin and cephalosporin resistant strains of Streptococcus pneumoniae has markedly increased. Global research about resistant respiratory pathogens (Alexander Project) has revealed penicillin resistant S. pneumoniae in different regions of the world (France, Spain) to be 51.4% of cases, and resistance against macrolides and co-trimoxasole to be 45.9% and 60.6% respectively.
 
In clinical practice it is important to separate those severe forms which have the following clinical signs:
-   Bilateral, patchy or abscessed pneumonias;
-   Rapidly progressive forms (infiltration zones increasing by 50% and more during 48 hours of observation);
-   Severe respiratory insufficiency;
-   Severe circulatory insufficiency, requiring vasopressor amine use;
-   Leukopenia (below 4.0) or leukocytosis more than 20.0X1000/mcL with neutrophil blasts >10% ;
-   Oliguria or other manifestations of acute renal failure.
 
During the course of severe pneumonia toxic shock syndrome (TSS), respiratory distress syndrome, disseminated intravascular coagulation (DIC), multi-organ failure and other lethal complications are often encountered.
 
After the diagnosing severe pneumonia promptly starting intravenous antibiotic therapy is considered to be mandatory. In the initial period of treatment (most challenging period) de-escalation therapy has been widely established, when the patients are treated with the wide spectrum antibiotic combinations to cover all the probable etiologic agents , before concrete diagnosis is being established.
 
In hospitals there are special regimens that can be used in treatment of community-acquired pneumonias, these regimens can be solely beta-lactam antibiotics (Ampicillin/Sulbactam, Amoxicillin/Clavulanic acid, Ceftriaxone) or their combination with Macrolides (Azitromicin , Spiramicin) in the case if suspicion is made about intracellular agents, respiratory flouroquinolones are also used. It is recommended to use β-lactams, and aminoglycosides and/or fluoroquinolones (Levofloxacine) combinations in very severe or abscessing pneumonias. In case of aspiration induced pneumonia suspicion, β -lactam antibiotic effective against gram negative organisms in combination with Amikacin (MERKACIN) and/or fluoroquinolones (Ciprofloxacine, Levofloxacine) and/or Metronidazole is given.
 
Aminoglycoside medications have been widely used in treatment of various forms of pneumonias, especially of the severe forms, since many years. The third generation aminoglycoside – MERKACIN (WORLD MEDICINE, England) – is well known among physicians and is widely used in treatment of respiratory infections (pneumonia, pleural empyema, the lung abscess). High sensitivity of the causative organisms toward MERKACIN makes it useful in the initial empiric therapy before complete microbial cultivation and sensitivity tests results are ready.
 
Today treatment of non-hospital acquired pneumonia is still problematic. Roughly gram negative causative agents are blue-green rods (Pseudomonads), E.coli, Klebsiella, Proteus spp., Enterobacter spp. and others against which MERKACIN is effective. It well penetrates and distributes in the tissues and fluids, including in pleural exudates and bronchial secretes, it has marked synergic action with β-lactam antibiotics, which increases its bactericidal action. MERKACIN has marked resistance against bacterial inactivating enzymes (apart from other Aminoglycosides) and is effective against resistant strains. In the zone of infection it maintains therapeutic concentration for 10-12 hours, and has marked post-antibiotic effect. Once a daily dosing increases its effectiveness and lowers risk of the side effects. There are two release forms of MERKACIN (500mg/2ml; 100 mg/2ml), which makes it easy to use in any age-group of the patients.
 
Reference:
 
1. Felmingham D., Gruneberg R. N., and the Alexander Project Group. The Alexander Project 1996- 1997: latest susceptibility data from this international study of bacterial patogens from community-aquired lower respiratory tract infections. Antimicrob Chemotherapy 2000;
2. Антибактериальная терапия. Практическое руководство. Под ред. Л. С. Страчунского, Ю. Б. Белоусова, С. Н. Козлова. Москва 2000.
3. Яковлев С.В. А.Г.Чучалин, А.И.Синопальников, Н.Е.Чернеховская; Тяжелая внебольничная пневмония; Москва – 2002.