Analysis of the Effectiveness of Antibiotic Therapy in Acute Bacterial Rhinosinusitis

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Published on International Journal of Health, Nursing, & Medicine
Publication Date: March, 2020

Ayu Angger Putri M. Soleh
Harapan Bangsa Health College Jember (STIKES)
Jember, East Java, Indonesia

Journal Full Text PDF: Analysis of the Effectiveness of Antibiotic Therapy in Acute Bacterial Rhinosinusitis (Studied of Pediatric and Adult Outpatients in the ENT Hajj Hospital, Surabaya).

Abstract
Antibiotics are indicated in the case of Acute Bacterial Rhinosimusitis, the administration of antibiotics should be guided by appropriate culture whenever possible, especially in patients who have failed in initial first-line antimicrobial therapy. This research will provide data on the effectiveness of antibiotics in the treatment process of Acute Bacterial Rhinosinusitis and patterns of microbial sensitivity to anibiotics in Acute Bacterial Rhinosinusitis. The affordable population in this study were all outpatients with Acute Bacterial Rhinosinusitis who received empirical and definitive antibiotic therapy at Haji Hospital Surabaya. The sampling technique in this study uses total sampling technique, which is one of the non-probability sampling techniques. The effectiveness of empirical and definitive antibiotics is assessed based on improvement of clinical conditions. The effectiveness data will be categorized into 2, namely “effective” and “ineffective”. If the patient experiences an improvement in the clinical condition and the results of the physical examination reveal that there is an improvement, then the use of antibiotics is considered effective, but if the opposite occurs, the antibiotics are considered ineffective. Sensitivity test results obtained include sensitive bacteria (S), intermediates (I) and resistant (R) to antibiotics. Pseudomonas aeruginosa bacteria analyzed in this study were still sensitive to Piperacilintazobactam. Antibiotics that are intermediate to Pseudomonas aeruginosa are meropenen and Piperacilin. The most common bacteria that cause infections are Pseudomonas aeruginoa, Enterobacter cloacae and Staphylococcus aureus. Infectious Disease Society of America (IDSA), states the prevalence of dominant pathogens in Maxillary Acute Rhinosinusitis for pediatric and adult patients (average percentage of specimen). Acute Bacterial Rhinosinusitis patients with bacteria that cause Staphylococcus aureus, Streptococcus haemolyticus and Enterobacter cloacae against administration of empiric antibiotics of clavulanate amoxicillin show effective. After conducting research for 3 months at Surabaya Haji Hospital, it can be concluded that the administration of antibiotic Amoxicillin Clavulanate is effective for use as a therapeutic treatment for Acute Bacterial Rhinosinusitis.

Keywords: Antibiotics, Acute Bacterial Rhinosimusitis, Patients, Therapy, Treatment, Effectiveness, Test Results for Using Antibiotics, and Bacteria.

1. INTRODUCTION
Rhinosinusitis is defined as inflammation of the paranasal sinuses and nasal cavity. Acute Rhinosinusitis starts when the virus infects the upper respiratory tract, then extends into the paranasal sinuses, which can be followed by bacterial infections. Simus puncture, which is performed for bacterial examination, is considered the gold standard for bacterial diagnosis. The most common bacteria of pediatric and adult patients on Acute Bacterial Rhinosimusitis are Streptococcus pneumoniae, Haemophilus influenzae, Morarella catarrhalis, and Streptococcus pyogenes.1
Goal of treatment in Acute Bacterial Rhinosinusitis is sinus drainage
and eradication of pathogenic bacteria. Antibiotics are indicated in the case of Acute Bacterial Rhinosimusitis, the administration of antibiotics should be guided by appropriate culture whenever possible, especially in patients who have failed in initial first-line antimicrobial therapy. The development of germ resistance to antibiotics is strongly influenced by the intensity of antibiotic exposure in an area, uncontrolled use of antibiotics tends to increase the resistance of germs that were initially sensitive. The discovery of MDR, the selection of appropriate antibiotics will be a problem, including cost constraints. Most use of antibiotics occurs in hospitals, so in its management should have a program to control infection, control of resistant germs, create a new guideline for the continuous use of antibiotics and monitor antibiotic use in hospitals.1,8
Based on these reasons, we want to do a research that aims to find out the effectiveness of antibiotics in the treatment of Acute Bacterial Rhinosinusitis in Haji Hospital Surabaya. It is hoped that the results of this study will be able to be used as one of the recommendations for formulating an appropriate antibiotic use policy, to prevent and control resistance and infection associated with Acute Bacterial Rhinosinusitis. What is the effectiveness of antibiotic therapy for the treatment process of Acute Bacterial Rhinosinusitis? The general objectives of the study are: Effectiveness of the administration of antibiotic therapy to the treatment process of Acute Bacterial Rhinosinusitis The specific objectives of the study are:
a. Knowing the bacteria that causes Acute Bacterial Rhinosinusitis.
b. Knowing the pattern of germs and bacterial sensitivity to antibiotics in Acute Bacterial Rhinosinusitis.
c. Knowing alternative antibiotics that can be used in Acute Bacterial Rhinosinusitis.
This research will provide data on the effectiveness of antibiotics in the treatment process of Acute Bacterial Rhinosinusitis and patterns of microbial sensitivity to anibiotics in Acute Bacterial Rhinosinusitis.

2. LITERATURE REVIEW
2.1 ACUTE BACTERIAI RHINOSINUSITIS
Acute Bacterial Rhinosinusitis (ABRS) is a condition characterized by inflammation of the paranasal cynical membrane that occurs due to 5 to 7 days after infection with vurus, bacteria, fungi or allergens in the upper respiratory tract.8

2.2 CLASSIFICATION OF RHINOSINUSITIS BACTERIAL ACUTE
Acute Bacterial Rhinosinusitis can be classified based on the size of the largest paranasal sinus, namely the maxillary sinus (located on the cheek), frontalis sinus (located on the forehead), ethmoid sinus (between the two eyes) and sphenoidalis; pathogens (viruses, bacteria, fungi); complications (orbital, intranial), and other factors (nasal polyposis, immunosuspension, anatomical variants).

2.3 PARANASAL SINUS ANATOMY
The paranasal sinuses (maxillary, ethmoid, frontal, and sphenoid) consist of four air-filled spaces coated by pseudostratified, columnar epithelium and ciliated. Mucus formed in the paranasal sinuses is born into the nasal meatus

Figure 2.1 Anatomy of the Paranasa Sinus
The flow starts from the frontal sinus, etmoid arterior cells, and the maxillary sinus then enters the meatus-medius. Clinically, the important part is the ostiomeatal complex. The Ostiomeatal complex is a gap in the lateral wall of the nose that is bounded by the media concha and lamina papyrase. This area is important because almost all the channel holes of the paranasal sinuses are there. Ostiomeatal Complex (OMC) as a place for ventilation and as a drainage path for the frontal sinus, ethmoidalis, and maxillary.

2.4 PATHOPHYSIOLOGY ACUTE BACTERIAI RHINOSINUSITIS
The pathophysiology of rhinosinusitis involves 3 important elements:
1. Sinus ostia obstruction
Sinus ostia obstruction prevents mucous drainage. Ostia can be blocked by the mucosa of the brain or local causes (for example, trauma and rhinitis), as well as by certain systemic inflammatory related disorders and immune disorders. Mechanical obstruction due to nasal polyps, salty objects, septal deviation, or tumors can also cause ostial blockage. Specifically, anatomic variations that narrow the ostiomeatal complex, including the division of the septum, the paradoxical concha media, and Haller cells make this area more sensitive to obstruction due to mucosal inflammation.
2. Interruption of the Ciliary Function
Metacronus coordination of the columnar columnar epithelial cells pushes sinus contents toward the sinus ostia. Any dysfunction of the cilia causes fluid accumulation in the sinuses. Poor ciliary function can result from loss of ciliated epithelial cells; high air flow; viral, bacterial, or siliotoxin environment; inflammatory mediators; relationship between two mucosal surfaces; scar; and Kartagener’s syndrome.
3. Changes in mucous quantity and quality
If the composition of the mucus changes and the mucus produced is thicker (for example, as in cystic fibrosis), transport to the ostia is much slower, and the gel layer proves to be thicker. This results in a collection of thick mucus that is still retained in the sinuses for various periods. Faced with a lack of secretion or loss of moisture on the surface which cannot be compensated by mucous glands or goblet cells, the mucus becomes thicker and the sol phase can be very thin so that it allows the gel phase to have intense contact with the cilia and inhibit their movement. Excess mucus can flood the mucociliary cleaning system.2,4

2.5 SINUS PUNCTURE
Sinus puncture is the most accurate way to determine which organisms cause sinusitis and to define pathogenic organisms when standard therapy fails or in high-risk immunocompromised patients. Sinus puncture is an invasive procedure, so it is not done routinely

2.6 MICROBIOLOGY ACUTE BACTERIAI RHINOSINUSITIS
Patients with viral sinusitis develop into acute bacterial infections, this is generally caused by facultative aerobic bacteria (ie, S. pneumoniae, H. influenzae, and M. catarrhalis).

2.7 ANTIMICROBIAL AGENTS
Initial therapy in patients with infections is often given empirically and guided by clinical presentations. Antimicrobial agents used are broad spectrum (sometimes in combination with antimicrobial agents). Empirical therapy is carried out, because microbiological results are not available in 24 to 72 hours.

2.8 ANTIMICROBIAL RESISTANCE
The mechanism of bacterial resistance to antibiotics:
Genetic of antibiotic resistance:
a. Mutation. Mutations occur due to errors of replication or repair errors from damaged DNA
b. Hypermutators. Some bacterial cells can increase mutations from 10-50 times to 10,000 times.
c. Horizontal gene transfer
d. Transfer of resistant genes from one bacterium to another is called horizontal gene transfer. The main mechanism of this transfer process is plasmid transfer, transfer with viral media, and transfer by free DNA.
e. Adaptive mutagenesis. Most mutations occur during the process of cell division, but can also occur when cells do not divide or divide slowly. Mutations that occur only during the nonlethal selection phase, are called adaptive mutations.

3. RESEARCH METHODS
3.1 RESEARCH DESIGN
This research is an observational descriptive study and the data will be taken prospectively (prospective descriptive study). Descriptive research is research that aims to report numbers without looking for cause-effect relationships.13 This study aims to describe the effectiveness of antibiotic therapy related to the process of treatment of Acute Bacterial Rhinosinusitis and find out other alternative antibiotics that can be recommended.

3.2 CHANGE PARAMETERS OF CLINICAL CONDITIONS
3.2.1 Effectiveness of Empirical and Definitive Antibiotic Therapy
The effectiveness of antibiotic therapy in this study was assessed based on parameters indicating an improvement in clinical condition and no other complications.
Assessment of improvement of clinical conditions based on the decision of the ENT specialist doctor performed on the 4th day or when the first control patient was in the ENT Poly and on the 7th day from the start of antibiotic therapy.

3.2.1.1 Empirical Antibiotic Therapy
Empirical antibiotic therapy referred to in this study is the administration of antibiotics to treat acute bacterial rhinosinusitis before the causative organism is identified and sensitive antibiotics are determined. The selection of types, dosages and frequency of antibiotics is adjusted to the Clinical Practice Guidance (PPK) of ENT Poly Haji Hospital Surabaya.

3.2.1.2 Definitive antibiotic therapy
The definitive antibiotic therapy referred to in this study is the administration of antibiotics for specific microorganisms that cause Acute Bacterial Rhinosinusitis and the sensitivity of known antibiotics in each patient during the study period.

3.3 POPULATION & SAMPLE
The target population in this study were all patients with Acute Bacterial Rhinosinusitis. The affordable population in this study were all outpatients with Acute Bacterial Rhinosinusitis who received empirical and definitive antibiotic therapy at Haji Hospital Surabaya during November 2016 – January 2017.
The sampling technique in this study uses total sampling technique, which is one of the non-probability sampling techniques. Total sampling is a sampling technique where the number of samples is equal to the population. The recruitment process is carried out until the sampling deadline is over.

3.4 ETHICAL CONSIDERATIONS
The research proposal that has been compiled by researchers has been submitted to Surabaya Haji Hospital for a review by the Surabaya Haji Hospital Ethics Committee. After going through the research proposal examination process and obtaining a permit that was signed by the chairman of the Surabaya Haji Hospital ethics committee, this research could be carried out. Before conducting data collection, researchers need to provide an explanation to the research subjects regarding the flow of research, the risks that might occur if participating in the research, the benefits of the study, the confidentiality of the data taken and explain who can be contacted if there are questions about this research, then if the subjects are willing In this study, the subjects were asked to sign an informed consent. There are 2 sheets of informed consent that must be signed by the patient, i.e. the patient consent information sheet can be seen in appendix 2 and the consent statement sheet. The statement of consent form can be seen in appendix 3. The statement of consent form form will be signed by the researcher and the patient’s family. Informed consent was made in the form of 2 copies, where 1 sheet to be submitted to the patient and 1 sheet to the researcher.

3.8 DATA ANALYSIS TECHNIQUE
1. Data Collection
a. Collecting patient database (including medical record number, patient name (with initials), patient age, gender, date of visit to hospital, history of allergies, diagnosis) and data on the patient’s clinical condition from medical records.
b. Collecting data on empirical antibiotic therapy from medical records or drug use records.
c. Collecting data on the results of bacterial culture and testing its sensitivity to antibiotics from the Microbiology Laboratory of Surabaya Haji Hospital.
d. Collecting data on definitive antibiotic therapy from medical records or records of drug use that includes the type, dose and frequency of administration.
e. Collecting research data on effectiveness on day 4 after administration of empirical antibiotics and day 7 from the start of antibiotic therapy. Recording the effectiveness of antibiotics is done through observations on improving the clinical condition of patients obtained from medical records.

2. Analysis of the effectiveness of Empirical and Definitive Antibiotics
The effectiveness of empirical and definitive antibiotics can only be analyzed descriptively and cannot be analyzed statistically because there is only a small amount of available data, if a statistical test is performed it can be ascertained that the results are biased.
The effectiveness of empirical and definitive antibiotics is assessed based on improvement of clinical conditions. The effectiveness data will be categorized into 2, namely “effective” and “ineffective”. If the patient experiences an improvement in the clinical condition and the results of the physical examination reveal that there is an improvement, then the use of antibiotics is considered effective, but if the opposite occurs, the antibiotics are considered ineffective.

4. RESEARCH RESULT
4.1 Bacterial Sensitivity Pattern Causes Acute Bacterial Rhinosinusitis AgainstAntibiotics
Sensitivity test results obtained include sensitive bacteria (S), intermediates (I) and resistant (R) to antibiotics. Pseudomonas aeruginosa bacteria analyzed in this study were still sensitive to Piperacilintazobactam. Antibiotics that are intermediate to Pseudomonas aeruginosa are meropenen and Piperacilin.
Based on table 4.3, Pseudomonas aeruginosa shows resistance to 14 types of antibiotics. Resistance is also found in isolates of Enterobacter cloacae, bacteria resistant to penicillin antibiotics (ampicillin, amoxicillin kalvulanate), cephalosporins (cephazolin) and macrolides (erythromycin, clindamycin). Enterobacter cloacae is sensitive to 19 types of antibiotics, Staphylococcus aureus is resistant to amoxicillin and cefixim antibiotics. whereas Streptococcus haemolyticus is resistant to oxacillin and colistin.

Table 4.1 Table Percentage of Frequency of Sensitivity of Bacteria in the Result of Maxillary Sinus Culture on Provision of Antibiotic Therapy

Information:
S (Susceptible): A category that shows that bacterial isolates can be inhibited at minimum mineral concentrations of certain antibiotics
I (Intermediate): A category that shows that bacterial isolates can be inhibited at the minimum inhibitory concentration of certain antibiotics but with a lower response than sensitive categories
R (Resistant): A category that indicates that bacterial isolates cannot be inhibited at the minimum inhibitory concentration of certain antibiotics.

4.2. Effectiveness of Empirical and Definitive Antibiotics Prescribed in Patients with Acute Bacterial Rhinosinusitis
Data on antibiotic effectiveness was obtained from patient medical record data. Data are presented separately for each empirical antibiotic and definitive antibiotic. Based on the discovery of germs or not, antibiotic therapy can be divided into two, namely empirical therapy and definitive therapy.

4.2.1 Effectiveness of Empirical Antibiotics
The selection of empirical antibiotic therapy given to patients with Acute Bacterial Rhinosinusitis in Haji Hospital Surabaya is based on the Permanent Procedure of Haji Hospital Surabaya or Clinical Practice Guidelines (PPK) on Procedure for ENT-KL Case 2014-2016. The effectiveness of empirical antibiotics is assessed at day-to-day visits 4 post-treatment until bacterial culture results and sensitivity tests were obtained from the Clinical Microbiology Laboratory of Surabaya Haji Hospital. The effectiveness data will be categorized into 2, namely “effective” and “ineffective”. If the patient experiences an improvement in clinical condition (inflammation of the sinus mucosa, secretions and water’s radiograph) and the results of the physical examination indicate an improvement, then the use of definitive antibiotics is considered effective, but if the opposite happens, then definitive antibiotics are considered ineffective. Clinical success is defined as the resolution or improvement of signs and symptoms of Acute Bacterial Rhinosinusitis so that no further antimicrobial therapy is needed; Clinical failure is defined as a lack of improvement or worsening of symptoms of Aeute Bacterial Rhinosinusitis that requires further antimicrobial therapy.

4.2.2 Effectiveness of Definitive Antibiotics
The selection of definitive antibiotic therapy is based on the results of bacterial culture and sensitivity tests from the Clinical Microbiology Laboratory of Surabaya Haji Hospital. The examination of culture in the Microbiology Laboratory of Surabaya Haji Hospital, only included identification of gram-positive and gram-negative aerobic bacteria, while identification of anaerobic bacteria could not be done, due to the unavailability of conditions that support the growth of anaerobic bacteria. The sensitivity test in this study was carried out by the disk diffusion method. Data obtained from the Microbiology Laboratory of Surabaya Haji Hospital, where the data will include the nature of bacterial sensitivity, namely: susceptible, intermediate or resistant. This assessment is based on the measurement of antibiotic inhibition zones on the growth of bacterial culture.
The effectiveness of definitive antibiotics was assessed at the 7th post-treatment visit. If the patient experiences an improvement in clinical condition (inflammation of the sinus mucosa, secretions and water’s radiograph) and the results of the physical examination indicate an improvement, then the use of definitive antibiotics is considered effective, but if the opposite happens, then definitive antibiotics are considered ineffective. Data on the evaluation of definitive antibiotic effectiveness.

5. DISCUSSION
The diagnosis of Acute Bacterial Rhinosinusitis in this case is based on history, physical examination, transillumination examination and examination of benefits such as radiology with water’s. Radiology with water shows mucosal thickening or air fluid level in the diseased sinuses. Water’s sinus X-ray projection is useful for evaluating the maxillary sinus.

5.1 PATIENT CHARACTERISTICS
Based on Table 4.1, Acute Bacterial Rhinosinusitis patients were male with 1 patient and 3 female patients. Patients aged <11 years were 2 patients and 2 patients> 50 years. Based on European Position Paper data on Rhinosinusitis and Nasal Polyps in 2017, age <50 years is the most suffering from rhinosinusitis. Research by Yoshiurs et al. in Japan 68 sinusitis patients studied, the average age of most patients at the age of 46 years.11,12 From some of the research data it can be seen that rhinosinusitis is more common in young adults. This is presumably because paa young adults or productive ages are more likely to be often exposed to allergens and have been exposed to pollutants for longer periods so that moreover can occur Acute Bacterial Rhinosinusitis at that age can interfere with its production. The results of this research have not been able to show the highest proportion of age that can be affected by Acute Bacterial Rhinosinusitis in RSU Haji Surabaya. Based on the work in Table 4.1, 2 patients were students, 1 patient worked as a driver and 1 patient was an entrepreneur. In this study found students, because students most often move outside the home so often exposed to pollutants such as smoke or dust or irritants that can cause mucosal changes and damage the cilia that can ultimately increase the occurrence of Acute Bacterial Rhinosinusitis. 5.2 BACTERIAL PATTERNS ON SUSTAINARY SPECIMEN SPECIMENS Based on Table 4.2, examining 10 specimens taken from maxillary sinus, only 4 specimens showed positive bacterial growth and 6 specimens showed no bacterial growth. The bacteria found are gram-negative bacteria (Pseudomonas aeruginoa, Enterobacter cloacae) and gram-positive bacteria (Staphylococcus aureus, Streptcccus haemlyticus). Based on data on bacterial patterns and sensitivity at the Surabaya Haji General Hospital for the period of 2015, the most common bacteria that cause infections are Pseudomonas aeruginoa, Enterobacter cloacae and Staphylococcus aureus. Infectious Disease Society of America (IDSA), states the prevalence of dominant pathogens in Maxillary Acute Rhinosinusitis for pediatric and adult patients (average percentage of specimen) reported before 2000 and in 2010. Indicates that the most frequent pathogenic bacteria are Streptococcus pneumoniae and Haemophilus influenza, Staphylococcus aureus, Steptrococcus pyogenes, Enterobacteriacae spp are relatively rare pathogens in acute axillary sinusitis. The prevalence of negative specimens (absence of bacterial growth) is also relatively frequent in acute maxiary sinusitis. 5.3 BACTERIAL SENSIVITY 5.3.1 Pattern of Gram Negative Bacteria Sensitivity to Acute Bacterial Rhinosinusitis Against Antibiotics In the sensitivity test results of table 4.3, gram-negative bacteria Pseudomonas aeruginosa showed resistance to more than 6 classes of antibiotics. Pseudomonas aeruginsoa isolate in this study still shows its sensitivity to Piperacilin tazobactam. Tazobactam complements the work of Piperacilin by binding to the β-lactamase enzyme so that it permanently causes the β-lactamase enzyme to no longer be active and cannot interfere with Piperacilin’s action. Meropenem and Piperacilin show intemediate to Pseudomonas aeruginosa. Meropenem is broad spectrum, this class of antibiotics are 3rd line antibiotics where the first line and second line antibiotics are no longer effective. 16,17,18 One gram-negative bacterial isolate Enterobacter cloacae is sensitive to 19 antibiotics and there is resistance to 5 anatibiotics including antibiotics Cephazolin, Ampicillin, Amoxicilin Kavulanat, Erithromycin and Clindamycin. Based on data on bacterial patterns and sensitivity at the Surabaya Haji General Hospital for the period of 2015, Enterobacter cloacae showed 60% sensitive to Gentamicin, Amikacin, Nitrofurantoin, Meropenen, Phosphomycin, Piperazilin Tazobactam and Cefoxitin. 5.3.1 Pattern of Gram Positive Bacteria Sensitivity to Acute Bacterial Rhinosinusitis Against Antibiotics GRM positive bacterial isolates Staphylococcus aureus showed resistance to amoxicillin and cefixime antibiotics, resistance that occurs is closely related to the potential occurrence of MRSA epidemics (Meticillin resistant Staphylococcus aureus). resistant to Oxacillin and Colistin. Resistance that occurs due to Oxacillin is called anti-Staphylococcus penicillin which has a narrow spectrum antimicrobial activity. 5.4 ANTIBIOTIC EFFECTIVENESS 5.4.1 Effectiveness of Empirical Antibiotics All patients in this study received empirical antibiotics of clavulanate moxicillin. The choice of empirical antibiotics for treating Acute Racterial Rhinosinusitis is outlined in appendix 2, most guidelines recommend amoxicillin as first-line therapy because of its safety, effectiveness, low cost, and narrow microbiological spectrum. The results of the effectiveness of using empirical antibiotics are in Table 4.4. Acute Bacterial Rhinosinusitis patients with bacteria that cause Staphylococcus aureus, Streptococcus haemolyticus and Enterobacter cloacae against administration of empiric antibiotics of clavulanate amoxicillin show effective. Patients with bacteria that cause Pseudomonas aeruginosa have received empirical antibiotic Amoxicillin Clavulanate syr at a dose of 3 x 2 cth. Infectious empirical antibiotic Disease Society of America (IIDSA) recommends amoxicillin clavulanate better than single Amoxicillin in children with Acute Bacterial Rhinosinusitis. The recommended high dose of clavulanate amoxicillin in children is 90 mg / kg / day orally twice a day. Sedian circulating in Indonesia, namely, Amoxicillin Clavulanate in the form of a syrup, with each 5 ml of syrup containing: Amoxicillin Trihydrate is equivalent to Amoxicillin 125 mg and Clavulanic Potassium is equivalent to 31.25 mg Clavulanic Acid. Doses can be given 10 ml, 3 x 1. Based on table 4.4 Pseudomonas aeruginosa against empirical antibiotics Amoxicillin Clavulanate shows treatment failure based on clinical conditions and clinical examination. Therefore, the antibiotic Amoxicillin Clavulanate against Pseudomonas aeruginosa is ineffective. 5.4.2 Effectiveness of Definitive Antibiotics Based on the results of bacterial sensitivity tests to antibiotics from the Microbiology Laboratory of Surabaya Hajj Hospital (table 4.3). Sensitive antibiotics are definitive antibiotics that can be recommended in patients with Acute Bacterial Rhinosinusitis. All patients in this study received the definitive antibiotic Amoxicillin Clavulanate. The definitive antibiotic given to patients with Acute Bacterial Rhinosinusitis with the bacteria that causes Staphylococcus aureus is to continue the empirical antibiotic therapy of amoxicillin clavulanate 3 x 2 cth. Provision of definitive antibiotic Amoxicillin Clavulanate is combined with physiotherapy therapy. The duration of clavulanate amoxicillin antibiotic therapy is 14 days. In this case after the management of definitive antibiotic Amoxicillin Clavulanate with physiotherapy showed improvement in clinical conditions. In this case the definitive antibiotic Amoxicillin Clavulanate is effective. Research conducted by Eli Hosoien et all. find out whether there is a difference between the effects of ultrasonographic exposure and antibiotic therapy (amoxicillin) on pain and short-term Acute Bacterial Rhinosinusitis congestion. The experimental group received 4 days consecutive ultrasonographic therapy and the control group received 10 days consecutive antibiotic therapy. Once entered day 4, pain around the nose decreased by 1.5 in from 10 (95% CI 0.6-2.5) more in the experimental group than in the control group. There were no other differences in pain reduction and congestion between groups on day 4 or day 21. The results of this study indicate that ultrasonographic therapy is an alternative to antibiotic therapy in the management of Acute Bacterial Rhinosinusitis. Ultrasound intensity increases the antibiotic bactericidal action of bacteria in vitro and in vivo, including Planktonic bacteria, Biofilm bacteria, Chlamydia, and bacteria in the implant. This literature shows that low intensity ultrasound alone is not effective in killing bacteria, whereas the combination of low intensity ultrasound and antibiotics is promising. Acute Bacterial Rhinosimusitis patients with bacteria that cause Streptococcus haemolyticus have improved clinical conditions. The results of sensitivity culture test, obtained Amoxicillin Clavulanate is sensitive to Streptococcus haemolyticus, therefore, the definitive antibiotic Amoxicillin Clavulanate in this case is effective. The patient received the definitive antibiotic Amoxicillin Clavulanat which was not in accordance with the results of the bacterial sensitivity test to the antibiotic. The incompatibility of this definitive antibiotic was deciphered because the culture results and the sensitivity test from the Microbiology Laboratory of Surabaya Haji Hospital were only obtained on the fifth day or after the patient had done control. Laboratory results show that Amoxicillin Clavulanate is resistant to Enterobacter cloacae. Evaluate the patient’s clinical condition for 6 days after receiving the Amoxicillin Clavulanate antibiotic, which is an improvement in the clinical condition. Improvement of clinical conditions is not in accordance with the results of the microbiology laboratory. Antibiotics are anti-prosthetic substances produced by various species of microorganisms that can suppress growth and or kill other microorganisms. However, this case shows that Amoxicillin Clavulanate has been resistant to Enterobacter cloacae. Evaluation of clinical conditions was assessed based on history, physical examination, transillumination examination and supporting examinations such as radiology with Water’s X-ray sinus projection Waters in this case performed Acduakalinya useful for evaluating the maxillary sinus. Photographs show a normal sign on the sinus that is, there is no limit of air fluid (water una level) in the sinus. Comparison of the Pehlama Waters projection sinus X-rays and the two covered a significant difference. Definitive antibiotics that can be recommended in the case of Pseudomonas, namely sensitive antibiotics (Piperacilin-Tazobaktam) and intermediate antibiotics (Piperacilin and Meropenem). However, Piperacilin Tazobaktam and Piperacilin Antibiotics cannot be used in this case. Antibiotics Piperacilin and Piperacilin Tazobaktam are the same class of antibiotics. If Piperacillin is intermediate, there is a risk of resistance to Piperacillin Tazobaktam in this case. Meropenem is an intermediate antibiotic, it also worries clinicians to give antibiotics the last choice that can be given to patients. Therefore, clinicians take action that can be done in improving the clinical condition of the patient that is planned to be carried out Functional Endoscopic Minus Surgery (BSEF) while still considering giving Amoxicillin Clavulanate antibiotics. Therefore, the definitive antibiotic Amoxicillin Clavulanate in this case does not match the results of the sensitivity test and is not effective. 5.5 ALTERNATIVE ANTIBIOTIC THERAPY From the results of this research we can see that the most widespread spread and has a fairly high sensitivity test result is levofloxacin. Based on the IDSA Guideline, levofloxacin is an antibiotic recommended in patients with Acute Bacterial Rhinosinusitis. Concerned for antibiotic resistance or failure of initial therapy or the occurrence of severe infections that do not require hospitalization and no beta-lactam allergy, then recommendations that can be given are other antibiotics with a better sensitivity percentage than Amoxicillin-Klavulanate namely Levofloxacin. 5.6 LIMITATIONS OF RESEARCH Researchers have tried to carry out this research well, but of course there are still limitations in this study, namely: a. The number of research samples is small, if more samples are obtained then the results of this study will better be able to describe the real condition of the patient population of Acute Bacterial Rhinosinusitis. b. The limited number of isolates used to make antibiograms, so the sensitivity pattern of bacterial culture results to antibiotics in this study can only be used as an illustration only. 6. 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