ANTIBIOTICS IN THERAPY GROUP BETALAKTAM perforated acute suppurative otitis media

ANTIBIOTICS IN THERAPY GROUP BETALAKTAM 

perforated acute suppurative otitis media 

By: 

Tutut SRIWILUDJENG T. 

Dr. Wahidin Sudiro Husodo Mojokerto 

INTRODUCTION 

Acute suppurative otitis media (OMSA) is an acute infection of the tympanic cavity mukopiriosteum accompanied by the formation of purulent secretions (Harmadji, Soepriyadi, Wisnubroto, 2005). Bacterium Streptococcus pneumoniae causes common and Haemophilus influenzae, other, more rare bacteria Staphylococcus aureus, Streptococcus pyogenes, Branhamella Catarhalis (Harmadji, Soepriyadi, Wisnubroto, 2005). In culture isolates OMSA tympanic cavity 24 patients obtained 54% of Streptococcus pneumoniae, Haemophilus influenzae and Branhamella Catarhalis 25% 12.5% ​​(Rodique, et al, 1995). At OMSA Perforate obtained tympanic membrane is perforated parasintesis spontaneous or due to the action, accompanied mukopurulen discharge, perforation of tympanic membrane in pars always Tensa and small to large enough to discharge secretions (Shambough, Girgis, 1991). 

OMSA is the most common diseases due to respiratory complications at the age of the children. Based on research from the years 1977-1983 found 16 611 children born in Malmo, Sweden as much as 79% of male fund 77% of women experience episodes of OMSA. Various experienced the highest annual incidence of children aged 1 year (Ingvarsson, Lungdren, Stenström, 1990). At ENT-TOS URJ Dr Soetomo in 2003 there are 836 (8.29%) patients with OMSA, and in 2004 as many as 947 (10.6%) patients OMSA (Annual Report Unit Outpatient ENT Dr. Soetomo, 2003). 

Amoxicillin is an antibiotic choice for OMSA appropriate therapy and treatment guidelines at URJ TOS ENT-Dr. Soetomo. Provision of amoxicillin on perforated OMSA is still the standard therapy (Harmadji, Soepriyadi, Wisnubroto, 2005). Amoxicillin is effective against gram positive and gram negative. This antibiotic has bakteriosid effect on bacteria that are actively dividing. But now many reports of bacteria that are resistant to amoxicillin. effectiveness of amoxicillin against OMSA porforata been investigated in the year 2007 showed the recovery of about 55 (Rusbiantoro, 2007). Who in 1996 had reported healing OMSA porforata treated with amoxicillin at day 6 did not get as much as 74.3% otorrhoea (Djokosasono, Jogjohartono, Suprihati, 1996). In the United States based research OMSA 250 patients who were given amoxicillin for 10 days were evaluated on the 14th got ahri cure rate 92.8% (Saux, at al, 2005). 

Giving antibiotics in OMSA sanagt important to speed healing and prevent complications. Many kinds of antibiotics that can be used one of them is sefadroksil.Sefadroksil as first-generation cephalosporins are still rarely used. Research on the effectiveness of OMSA sefadroksil not been found, both at home and abroad. In vitro work Sefadroksil active against gram-positive bacteria but kuarang effective against gram negative. Anti-bacterial spectrum resembles a broad spectrum pinisilin, but sefadroksil more resistant to common antibiotics pinisilinase.secara is indicated for ear infections, OMSA, lower respiratory infections and above (Snyder, 1982). Sefadroksil is bactericidal, with mengahambat bacterial cell wall synthesis and sefadroksil peoral given twice daily. 

1. Anatomy of the tympanic cavity 

Tympanic cavity (middle ear cavity) is a six-walled air spaces but irregular in shape, elongated towards the anterior - posterior 15 mm and 15mm vertical, has a volume of approximately 0.25 cc. divided into three sections based on the limit superior and inferior tympanic membrane that is epitimpani or tweaking, mesotimpani and hipotimpani (Austin, 1991). 

a. Epitimpani 

Inside there epitimpani incus and malleus. In the section bounded by the superior tympanic tegmen, the medial wall formed by the capsule atik atik characterized by a bulge of the lateral semicircular canal. In the anterior part contained the superior canal ampulla, and more anterior ganglion genikulatum there. Lateral wall formed by the Os Skuama. In the posterior part narrows into the driveway tweaking (aditus ad antrum) to the mastoid (Austin, 1991). 

b. Mesotimpani 

Mesotimpani medial capsule is limited by tweaking. Right next to the tympanic membrane is seuatu medial protrusion of a curved at the basal cochlear called promontorium. Next to the superior posterior promontium on there at the foramen ovale and foramen rotundum are inferior. At the foramen ovale are located at the base of the stapes sagittal field. Mesotimpani posterior wall formed by the bones that covered the pars descending facial nerve, the superior side of this wall there is a cone-shaped protrusion called eminesia pyramid, protect and muskulus stapedius tendon (Austin, 1991). 

A space that is clinically very important is the posterior sinus or facial resesus, located on the lateral canal and the facial process of the pyramidal, this space extends from the middle ear space postero superior to aditus ad antrum and diseases are often hidden here (Austin, 1991). 

On the wall there are mesotimpanum anterior tympanic orifice Eustachius tuba in the superior and form part of the bone wall of the carotid canal on the ascending inferior (Austin, 1991). 

c. Hipotimpani 

A shallow space which lies lower than the tympanic membrane. Bone surface in this part looks like a picture of shellfish because of the air cells form a cup. This wall covering the jugular bulb (Austin, 1991). 

2. Acute suppurative otitis media 

2.1 Limitation 

Acute suppurative otitis media (OMSA) is an acute infection of mukoperiosteum cavity with accompanying formation of purulent secretions (Harmadji, Soepriyadi, Wisnubroto, 2005). Based on reports from the third research conference on Recent advences in otitis media, acute otitis media purulenta called acute otitis media or acute suppurative otitis media (paparella et al, 1985). 

In 1980 an ad hoc comitte on definition and classification of otitis media and otitis media with effusion announced about the limitations of the duration of acute pain from the beginning until the first 3 weeks, 0-21 days (Senturia et al, 1980). 

2.2 Incidence 

OMSA is the most common illness from complications of upper respiratory tract infection at the age child. Based on research from 1977 to 1983, found 16,611 children born in Malmo, Sweden, as many as 79% of boys and 77% of the daughters was recorded as having 13 990 and 11 921 episodes of OMSA. Experienced the highest annual incidence of children aged 1 year (Ingvarson, Lungdrem, Stenström, 1990) 

In poly-ENT clinic of Dr KL Soetomo, OMSA is still one of the most infectious diseases.In 2003 a new visitor at the clinic of ENT-TOS, totaling 10,083 patients, a total of 863 (8.29%) are people with OMSA and have ranked the 3rd most diseases in the clinic of ENT-TOS. Who's new visitors in 2004 amounted to 8937 patients, a total of 947 (10.6%) patients with OMSA and ranked 2nd highest in the URJ ENT disease-KL (URJ Report, 2003). 

2.4 Etiology 

OMSA occur because of expansion of infection from the nasopharynx and pouch of rice into the tympanic cavity through the fallopian Eustachius. Bacterium Streptococcus pneumoniae causes common and Haemophilus influenzae, other, more rare bacteria Staphylococcus aureus, Streptococcus pyogenes, Branhamella Catarrhalis (Harmadji, Soepriyadi, Wisnubroto, 2005). By Rodrique et al (1995) from culture isolates OMSA tympanic cavity in 24 patients found 54% of Streptococcus pneumoniae, Haemophilus influenzae and Branhamella Catarrhalis 25% 12.5% ​​Siguntang (1996) on research to get OMSA causing bacteria Pseudomonas aeruginosa that is perforated by 29 , 41%, 9.8% Streptococcus pyogenes, Staphylococcus aureus 7.8%. Pseudomonas aeruginosa and Staphylococcus aureus is a cause of secondary bacterial OMSA originating from outside the ear canal (Wlad, 1990). Type virus is the major cause of respiratory syncytial virus, Parainfluenzae virus, Influenza virus, entero virus and adeno virus (Heikkinen Thint, Chonmaitree, 1999). 

2.4 Pathophysiology 

The middle ear is usually sterile, although there are bacteria in the nasopharynx and pharynx. The physiological activity of cilia, enzyme and antibody serves as a defense mechanism when the middle ear are exposed to this contaminant bacteria during swallowing (Paparella, Adams, Levine, 1989). 

Disorders of the fallopian Eustachius a factor main cause of OMSA, generally preceded by upper respiratory tract infections because the virus through the formation of cytokines and inflammatory mediators, so that the mucosa became udim, including tubal Eustachius. Tubal mucosa Udim Eustachius cause obstruction of the fallopian mainly narrowest isthmus, which is part causing ventilation problems (Paparella, Adams, Levine, 1989; bluestone, 2001; Harmadji, Soepriyadi, Wisnubroto, 2005). Under normal circumstances, the middle ear is an enclosed space and filled with air. Middle ear mucosa gradually will absorb air and nitrogen from the middle ear so that eventually the air pressure in the ear will decrease. With the opening of the fallopian Eustachius periodically, then the air will come to balance again in the middle ear pressure. Tuba Eustachius a dead end cause negative pressure in the middle ear and place vacuum (bluestone, 1993). This will lead to changes in the mucosa of the tympanic cavity of the increased permeability of capillaries and lymph vessels, miningkatnya permeability of cell walls and cell proliferation, mucous gland cells. These changes cause fluid to enter the tympanic cavity (transudation) called hydrops ex vacuo, resulting in the middle ear is very susceptible to bacterial infections that come directly from the nasopharynx (Austin, 1991; Shambough, Girgis, 1991). ARI infection by the virus also plays a decline in defense capabilities upper respiratory tract mucosa in preventing displacement and settlement of bacteria, especially in the nasopharynx into the middle ear through the mucosa, giving rise occurred supurasi and OMA (Kentjono, 2006). 

2.5 Clinical Symptoms 

Symptoms of acute suppurative otitis media through several stages according to Shambough, Girgis, (1991) as follows: 

a. Stage 1 (hyperemia) 

At this stage begins with tubal mucosal hyperaemia Eustachius, tympanic cavity and mastoid cells. Lumen tubes become clogged accompanied by an increase in air pressure in the middle ear. The air in the middle ear is absorbed and causes the pressure becomes negative. 

As a result of pressure difference on both sides of the tympanic membrane. Got a feeling of fullness in the ear and conductive hearing loss is. Examination otoskopi looked hyperaemia and retraction of tympanic membrane. Can occur fever and ear pain but not severe. 

b. Stage 2 (exudate) 

The increased permeability of capillary walls and cause vasodilation of discharge containing serum, febrian, red blood cells and polimononuklear into the middle ear. At the same time accompanied by increased production of mucus from epithelial cells kuboid, so that the middle ear filled by exudate. Tympanic membrane looked bomban.This resulted in the occurrence of conductive hearing loss and severe ear pain, fever is generally very high, especially in infants. 

c. Stage 3 (supurasi) 

Tympanic membrane is perforated parasintesis spontaneous or due to the action. The existence of fluid out of the hole mukopurulen perforation. Ear pain and fever began to decrease. Perforation of tympanic membrane pars always Tensa and small to large enough to discharge exudates. Marked with a permanent hearing loss. 

Figure 2.1. OMSA perforated (Kavanagh, 2007) 

d. Stage 4 (Koalesen) 

Symptoms and signs at this stage still get the secretions mukopurulen for more than 2 weeks. Ear and mastoid pain feels more severe, especially at night, although usually milder than the stage of exudation. Fever is reduced and is still characterized by a conductive hearing loss. 

2.6 Treatment of OMSA 

Principle OMSA treatment with adequate antibiotics and drainage improvements. First-line oral antibiotics can be given Amoxicillin 500 mg 3 times daily or Erythromycin 500 mg 3 times per day or cotrimoxazole 2 x 480 mg per day, for children to diberiakn Amoxicillin dose of 50 mg / kg / day together with co-trimoxazole Erythromycin while 2 x 240 mg per day (Canafax, Giebink, 1994; Garbutt, et al, 2004; Harmadji, Soepriyadi, Wisnubroto, 2005). Old antibiotics 7-10 days (Harmadji, Soepriyadi, Wisnubroto, 2005).Meanwhile, according to Garbutt et al (2004) antibiotics can be given for 12-14 days at OMSA without koplikasi. When required to do drainage improvements to the granting of an oral decongestant drugs / topical and parasentesis / miringotomi (Austin, 1991; Harmadji, Soepriyadi, Wisnubroto, 2005). Decongestant drug pseudoephedrine can be given orally 3 x 30-60 mg per day for 7 days and nasal drops (solusio efedri 1%, oxymetazoline 0.05%). Symptomatic drug consists of analgesic and antipyretic (asetosal, paracetamol, antalgin) which can be given if there are symptoms (Mulyarjo et al, 1994; Donaldson, 2004). 

The effectiveness of amoxicillin against OMSA perforated been investigated in the year 2007 showed the recovery of 55% (Rusbiantoro, 2007). Whereas in 1996 had reported healing OMSA perforated treated with amoxicillin at day 6 did not get as much as 74.3% otorrhoea (Djokosasono, Jogjohartono, Suprihati, 1996). In the United States based on the study 250 patients who diberiakan OMSA amoxicillin for 10 days were evaluated on day-14 cure rates obtained 92.8% (Saux et al, 2005). 

Use sefadroksil for OMSA cases are still rare. Similarly, research on the use of this sefadroksil. Although one idikasi sefadroksil usage is an ear infection including OMSA.The dose for children is 30 mg / kg / day in divided doses every 12 hours. The dose for adults is 1-2 grams per day in divided doses, depending on whether the infection is mild or severe (Snyder, 1982). 

3. Antibiotics betalaktam class 

3.1 Amoxicillin 

Based on the bacteria that often cause OMSA, then amoxicillin is the first-line antibiotics and are given primarily for initial attack OMSA perforated and have not been getting treatment (Cnafak Giebink, 1994; Harmadji, Soepriyadi, Wisnubroto, 2005; Sack, 2005). 

Amoxicillin is a broad-spectrum antibiotic class. Penicillin was first discovered by Fleming and Florey developed by using cultures of Penicillium notatum. Penicillin is used in the treatment of penicillin divided into natural and semisynthetic penicillin.Semisynthetic penicillins obtained by changing the nature of the core chemical structure of penicillin that is acid 6 - amino penisilat. Penicillin is an organic acid consisting of a single nucleus with one side chain cyclic, cyclic core consisting of a ring betalaktam and tiozolidin. Side chain is a free amino group that can bind various types of radical, in this way it will be able to obtain various types of penicillin (Gan, Istiantoro, 1995). 

Figure 3.1. Chemical structure of amoxicillin (Gan, Istiantoro, 1995). 

Amoxicillin including semisynthetic penicillin which has the chemical formula of a-amino-p-hydroxybenxyl-penicillin (Gan, Istiantoro, 1995). 

Amoxicillin is bakteriosidik that works by inhibiting bacterial cell wall synthesis. This would have the effect of antibiotics on bacteria bakteriosidik the current divide. The bacteria are in a state of metabolic inactivity (not split) is practically not affected by this antibiotic, even if there are only bacteriostatic effects (Gan, Istiantoro, 1995). 

Amoxicillin is effective against both gram-positive bacteria and gram negative. These drugs are still quite effective against bacteria that cause most OMSA Streptococcus pneumoniae and Haemophilus namely influenzae. However this time it has been reported by bacteria that are resistant to amoxicillin was based on penicillinase production that can split ring betalaktam, so that it becomes a penisiloat acid that does not have anti-bacterial properties, especially staphylococcus (Gan, Istiantoro, 1995; Rodrique et al, 1995). Based on research Siguntang (1996) aerobic bacteria resistant to amoxicillin following Streptococcus pneumoniae 22.2%, 36.4% Haemophilus influenzae, Streptococcus pyogenes 20%, 75% Staphylocossus aureus and Pseudomonas aeruginosa 100%. Since amoksisilia been widely used type of microbe that was sensitive to the longer many are becoming resistant. The mechanism of resistance could be explained by as gram positive and penicillinase esktraseluler secrete relatively large amounts of bacteria and enzymes can not work autosilin causing tolerance to the drug properties (Gan, Istiantoro, 1995). 

Amoxicillin orally not affected by stomach acid. About 75% - 90% absorbed dilambung.Peak in serum levels of 6-8 mcg / ml, this concentration is achieved 1-2 hours after administration of amoxicillin 500 mg per oral. Absorbsinya not influenced food in the stomach. The dose for adults or children weighing over 20 kg of 750-1500 mg per day, divided into three doses. Children weighing less than 20 kg can be given 50 mg / kg body weight per day. approximately 20% of amoxicillin in the blood is bound by plasma proteins (Snyder, 1982). 

Amoxicillin in wide distribution in the body and plasma binding by only 20%, which enter into the enterohepatic circulation of bile menglami, but which is excreted with the feces is quite high. Amoxicillin penetrate the brain barrier and reach optimal weight. In premature infants and neonates of amoxicillin resulted in blood levels are higher and persist longer in the body. Amoxicillin relatively quickly eliminated and diekskrasi primarily through the kidneys. Approximately 50-70% of the dose excreted in the urine in the form of fixed (Kucers, Meek, 1987). 

Side effects of amoxicillin can occur in all manner of administration and of many organs, resulting in mild to fatal. The frequency of adverse events depending on the supply of drugs. In general, oral administration is more rarely cause side effects than parenteral common. Allergic reactions are the most common form of side effects ranging from urticaria to anailaki reaction. Provision of amoxicillin in the long term and high dose will cause nephropathy (Gan, Istiantoro, 1995). 

3.2 Sefadroksil 

Sefadroksil is a first generation cephalosporin class of antibiotics. Cephalosporin and penicillin classes of antibiotics including betalaktam. Cephalosporins derived from the fungus acremonium cephalosporium isolated in 1948 by Brotze. This fungus produces 3 kinds of antibiotics are cephalosporins, P, N and C. of the three antibiotics were developed from the many ways derifat semisynthetic cephalosporin such as cephalosporin C. sefadroksil derived from first-generation cephalosporin C which has the chemical structure of 7-amino-acids, which owns the complex ring sefalosporanat betalaktam and dehidrotriasin (Gan, Istiantoro, 1995). 

Cephalosporins produced by cephalosporium acremonium and has a structure similar to penicillin. Β lactam ring is the chemical structure associated with antibacterial activity.We have some cephalosporin preparations. The difference is in their stability to acids and resistance to inactivation by β lactamase from both positive and negative organisms. Antibacterial spectrum cephalosporins penicillin-like broad spectrum.Sefadroksil in vitro work Akif against aerobic gram-positive coccus bacteria such as staphylococcus aureus, streptococcus pyogenes, Streptococcus viridian and streptococcus pneumonia, but less active against gram-negative bacteria. However, cephalosporins is more resistant to penicillinase (Gan, Istiantoro, 1995; Snyder, 1982). 

Figure 3.2. Sefadroksil chemical structure (Gan, Istiantoro, 1995). 

Sefadroksil working mechanism similar to the amoxicillin where its receptor is a protein that is identical to the enzyme peptidoglycan, which serves to inhibit the formation of bacterial cell wall, causing autolosis bacterial cell wall. Sefadroksil resistant to the penicillinase produced by bacteria that can destroy the ring betalaktam, because it is resistant to germ-sefadroksil kuamn pengahsil penicillinase, it is because sefadroksil has two chains as antimikrobanya. Secreting germs like pseudomonas and enterobater sefalosporinase to destroy the ring of sefadroksil betalaktam (Gan, Istiantoro, 1995). 

Oral cephalosporins are the most widely prescribed antibiotics in the U.S.. In general, antibiotics are indicated for infection of the upper and lower respiratory tract. Also indicated for ear infections, throat including otitis media. Contra indications are in patients with known allergy to cephalosporins (Snyder, 1982). 

The first-generation cephalosporins are known to have greater activity against gram-positive organisms than against gram-negative bacteria. Among the organisms gram positi, sefadroksil effective against most gram-positive bacterial pathogens including staphylococci producing penisillinase. Sefadroksil is bactericidal, with sitesis inhibits bacterial cell wall peptidoglycan synthesis that is mengahambat which is the major bacterial cell wall (Gan, Intiantoro, 1995). 

Sefadroksil dose for adults is 1-2 grams per day in two divided doses every 12 hours, and given a minimum of seven days to reach the dose efektf whereas in children of administration of 30 mg / kg / day orally. Sefadroksil given orally as well absorbed through cernadan channels were not affected by food didlam stomach. Blood levels of 10 g / ml after a dose of 0.5 g every 6 hours, binding proteins in the body by 20%.Sawer Sefadroksil through blood so as to achieve the highest levels in the fluid pericardium. Indications sefadrosil used uintuk upper respiratory tract infection, acute otitis media and lower respiratory tract infections. Most sefadroksil in excretion in the form of intact through the kidney, probenecid may decrease excretion in the kidney (Gan, Istiantoro, 1995). 

Side effects that often happens is that allergic reactions occur urtikarea. In patients who are allergic to amoxicillin rare mild allergic sefadroksil. Anfilaksis reaction can occur when using high doses. Sefadroksil is a substance which, although less nephrotoxic compared with amoxicillin. Diarrhea, nausea, vomiting is an effect of the use sefadroksil (Gan, Istiantoro, 1995). 

4. Summary 

At OMSA perforated tympanic membrane experienced spontaneous or due perdorasi parasintesis actions that accompanied the release of caian mukopurulen. Common bacterial cause is Streptococcus pyogenes OMSA and Haemophilus influenza.Purchase adequate antibiotics may mepercepat healing. Antibiotics are effective class is used as a therapy betalaktam OMSA perforated. 

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