The Toxic Effect on Leukocyte Lineage of Antimicrobial Therapy in Urinary and Respiratory Infections
ORIGINAL ARTICLE
doi: 10.5455/medarh.2014.68.167-169
Published online: 31/05/2014 Published print: 06/2014
Med Arh. 2014 Jun; 68(3): 167-169 Received: April 20th 2014 | Accepted: May 28th 2014 © AVICENA 2014
The Toxic Effect on Leukocyte Lineage of Antimicrobial Therapy in Urinary and Respiratory Infections Dzelaludin Junuzovic1, Lejla Zunic2,3, Melika Dervisefendic2, Amira Skopljak4, Almir Pasagic4, Izet Masic3,4 Department of Urology, Clinical center of Sarajevo University, Sarajevo, Bosnia and Herzegovina 1 Health center Gracanica, Gracanica, Bosnia and Herzegovina2 Faculty of Health sciences, University of Zenica, Zenica, Bosnia and Herzegovina 3 Department of Family medicine, University of Sarajevo, Bosnia and Herzegovina 4 Corresponding author: Ass. prof. Lejla Zunic, PhD. Faculty for Health Sciences, University of Zenica, Zenica, Bosnia and Herzegovina. E-mail:
[email protected]
ABSTRACT Introduction: Antimicrobials are widely used in infectious diseases. Only the timely intervention will contribute to the positive outcome of the disease. Unjustified use of antimicrobial prophylaxis may have adverse effects, i.e., result in bacterial resistance to existing antimicrobials, as well as toxic effects on leukocyte lineage and other parameters of the blood. Goal: The goal of this study was to confirm that the antimicrobial therapy of urinary, gynecological and respiratory infections has a toxic effect on leukocyte lineage. Followed by lowered immunity and the emergence of risk for health complications especially in oncology and other immunodeficient patients for whom to apply pharmacotherapy it is necessary to have adequate immunity, or white blood cell count that is greater than 4.0x109/L. Material and methods: A prospective-retrospective study was conducted on a sample of 30 patients in a Primary Health Care Center in Gracanica during the period from March 01, 2013 until April 01, 2014. Testing of this sample was conducted by survey on health status and treatment, or on taking of antimicrobial therapy and other treatment regimens, with the referral diagnosis and determination of leukocytes count in by hematology counter SYSMEX. Results of leukocytes below and close to the lower reference values were statistically analyzed by Students t-test. Results: Mean WBC count in the group treated with antimicrobial therapy was 3.687±0.83 x109/L, in the group which during repeated infection did not use the antimicrobial therapy 5.09±1.04 x109/L, and in the control group of healthy subjects 7.178±1.038 x109/L. Statistical analysis with Student’s t test indicate highly significant differences between group of patients that used antimicrobial therapy with the group of patient that did not used antimicrobial during repeated infection (t=6.091; p=0.0001), as well as significant differences in mean WBC count of both of these groups and the controls (t=4.984; p=0.0001, and t=8.402, p=0.0001). Conclusion: Use of antimicrobial drugs leads to serious toxic reactions, or leukopenia. Indications for the use of antimicrobial therapy must be strictly followed, because banal, frequent infections are not indication for antimicrobial therapy. It is necessary to know the types of infection causes. Important is the proper and timely selection of antimicrobial therapy. When selecting the drug we should bear in mind its antimicrobial activity, pharmacokinetic and toxic properties, as well as patient health status. Possible is also the application of preventive medicine as well as other manner of solving infection. Key words: antimicrobials, toxic effects, WBC count.
1. INTRODUCTION Antimicrobial therapy involves the application of a remedy against the presumed cause, the microbes. Antimicrobials should have a strong enough chemotherapy activity only toward responsible microbes and limited toxicity to the host (1-6). Antimicrobials are widely used in infectious diseases. Only the timely intervention will contribute to the positive outcome of the disease (7-11). Unjustified use of antimicrobial prophylaxis may have adverse effects, i.e., result in bacterial resistance to existing antimicrobials, as well as toxic effects on leukocyte lineage and other parameters of the blood. Med Arh. 2014 Jun; 68(3): 167-169
This results in a new health problems caused by the decrease of the immunity due to leukopenia and neutropenia, disturbance of flora and electrolytes balance. This further requires a new pharmacotherapy: antimicrobial treatment–antibiotics, as protective, vitamins, immunostimulant drugs and electrolytes. Also notable are the costs for all that pharmacotherapy, immune therapy and necessary replacement therapy.
2. GOAL The goal of this study was to confirm that the antimicrobial therapy of urinary, gynecological and respiratory infections has a toxic effect on leukocyte lineage. Followed 167
By examining the leukocytes count at the end of the study period in all cases we have 20% to 30% (or 25%) higher leukocytes count.
The Toxic Effect on Leukocyte Lineage of Antimicrobial Therapy in Urinary andweRespiratory Infections In the study included a control group of 20 healthy respondents aged 19-25 years who had a WBC count in the range from 5.1 to 8.9x109/L.
3. MATERIAL AND METHODS A prospective-retrospective study was conducted on a sample of 30 patients in a Primary Health Care Center in Gracanica during the period from March 01, 2013 until April 01, 2014. Testing of this sample was conducted by survey on health status and treatment, or on taking of antimicrobial therapy and other treatment regimens, with the referral diagnosis and determination of leukocytes count in by hematology counter SYSMEX. Results of leukocytes below and close to the lower reference values were statistically analyzed by Students t-test.
4. RESULTS It is obvious that patients who have a referral diagnosis of urinary tract, gynecological and respiratory infections require the determination of the leukocytes count in the period from March 01, 2013 to April 01, 2014. Tests on a sample of 23 patients who used pharmacotherapy for present urinary, gynecological and respiratory infections Patients 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 Mean Std. dev. Student t
WBC with anti- WBC without microbial th. antimicrobial th. 1.8 2.9 2.3 3.1 2.9 3.8 3.0 3.9 3.0 4.0 3.3 4.6 3.4 4.6 3.7 5.0 3.7 5.7 3.8 5.6 3.9 5.7 3.9 5.8 4.0 4.8 4.0 4.9 4.1 5.6 4.1 5.8 4.2 5.8 4.3 5.5 4.5 6.4 4.8 6.2 4.9 6.4 4.9 6.6 2.3 4.5 3.687 5.0957 0.834 1.042 t=6.091; p=0.0001 t=4.984; p=0.0001 t=8.402
WBC control group 5.1 5.8 6.0 6.1 6.2 6.3 6.5 6.7 6.8 7.0 7.1 7.4 7.4 7.5 7.6 7.8 8.2 8.4 8.5 8.6 8.7 8.8 6.6 7.1783 1.038
p=0.0001
Table 1. Number of leukocytes in patients with and without antimicrobial therapy and the control group
168
10 9 8 7 Leukocyte
by lowered immunity and the emergence of risk for health complications especially in oncology and other immunodeficient patients for whom to apply pharmacotherapy it is necessary to have adequate immunity, or white blood cell count that is greater than 4.0x109/L.
6 5
Lkc. with antimicrobial th.
4
Lkc. without antimicrobial th.
3
Lkc. control group
2 1 0
0
5
10
15
20
25
Patients
Figure 1. Leukocytes counts of patients with and without antimicrobial therapy and the Figure 1. Leukocytes counts of patients with and without antimicontrol group.
crobial therapy and the control group.
Table 1. Number of leukocytes in patients with and without antimicrobial therapy and the control group are carried out by survey and leukocytes count. Results
show that the number of leukocytes in 80 % of cases at or Patients withoutor inWBC near the lower level ofWBC thewith referenceWBC range, 24 control casesgroup antimicrobial th. antimicrobial th. we1 had mild to moderate leukopenia. 1.8 2.9 5.1 2 2.3 3.1 5.8 During the study to patients was suggested (in consul3 2.9 3.8 6.0 tation with their doctors) that in case of repeated urinary, 4 3.0 3.9 6.1 5 3.0 4.0 not to use spe6.2 gynecological and respiratory infections 6 3.3 4.6 6.3 cific antimicrobial therapy but urinary antiseptic, as well 7 3.4 4.6 6.5 5.0 6.7 as8other antiseptics and3.7immune stimulating pharmaco9 3.7 5.7 6.8 therapy. 10 3.8 5.6 7.0 11 examining the leukocytes 3.9 By count5.7at the end of 7.1the 12 3.9 7.4 study period in all cases we have 20%5.8 to 30% (or 25%) 13 4.0 4.8 7.4 14 4.9 7.5 higher leukocytes count.4.0 In the study we included a control group of 20 healthy respondents aged 19-25 years who had a WBC count in the range from 5.1 to 8.9x109/L. As we can see from the Figure and Table 1 the mean WBC count in the group treated with antimicrobial therapy was 3.687±0.83 x109/L, in the group which during repeated infection did not use the antimicrobial therapy 5.09±1.04 x109/L, and in the control group of healthy subjects 7.178±1.038 x109/L. Statistical analysis with Student’s t test indicate highly significant differences between group of patients that used antimicrobial therapy with the group of patient that did not used antimicrobial during repeated infection (t=6.091; p=0.0001), as well as significant differences in mean WBC count of both of these groups and the controls (t=4.984; p=0.0001, and t=8.402, p=0.0001).
5. DISCUSSION Uncritical use of antimicrobial drugs carries many risks, the occurrence of severe toxic reactions as in our case leukopenia and the development of resistant strains of bacteria, disruption of the normal bacterial flora (and the possibility of superinfection), the occurrence of hypersensitivity to the drug. Empirical antibiotic-antimicrobial therapy may be more harmful than helpful because of its often unjustified use for prophylactic purposes and not in therapeutic application as which has the consequence of new health problems. Patients are often infected with opportunistic organisms that are far more resistant to antimicrobials. As a consequence we have economic problems because of the steady increase in the total cost of the medication, both Med Arh. 2014 Jun; 68(3): 167-169
The Toxic Effect on Leukocyte Lineage of Antimicrobial Therapy in Urinary and Respiratory Infections
for the patient and the health insurance fund (the cost of antibiotics amount to 1/3 of the total heal care costs).
REFERENCES 1.
Rang HP, Dale MM, Ritter JM, Moore PK. Farmakologija. 5th edition, translation of the book: Pharmacology. Data status, Beograd, 2005.
6. CONCLUSION Use of antimicrobial drugs leads to serious toxic reactions, or leukopenia. In our sample 80% of patients with antimicrobial therapy had by 20-30% reduction in the number of leukocytes in relation to the tests conducted on the same patients without antimicrobial therapy in case of reinfection. Indications for the use of antimicrobial therapy must be strictly followed, because banal, frequent infections are not indication for antimicrobial therapy. It is necessary to know the types of infection causes. Important is the proper and timely selection of antimicrobial therapy. When selecting the drug we should bear in mind its antimicrobial activity, pharmacokinetic and toxic properties, as well as patient health status. Possible is also the application of preventive medicine as well as other manner of solving infection. CONFLICT OF INTEREST: NONE DECLARED
2.
Šibalić S. Antimikrobna sredstva i ljekar praktičar. Printcom, Tuzla, 2008.
3.
Varagić VM, Milošević MP. Farmakologija, XV prerađeno i dopunjeno izdanje, Beograd 1999.
4.
Vučetić JI. Mikrobiološke sinteze antibiotika. Velarta, Beograd, 1998.
5.
Hukić M. i sar.: Bakteriologija. Jež, Sarajevo, 2005.
6.
Registar lijekova sa osnovama farmakoterapije. Federalno ministarstvo zdravstva, Udruženje farmakologa Federacije BiH, Jež, Sarajevo 2009.
7.
Riley MA, Chavan MA. Bacteriocins Ecology and Evolution. Springer, New York, 2007.
8.
Harrison G. Principi interne medicine, prevod trinaestog izdanja knjige Principles of Internal medicine. Placebo, Split, 1997.
9.
Varma A, Podila GK. Biotechnological Applications of microbes. Microbiology series, New Delhi, 2005.
10.
Cascales E, Buchanan SK. et al. Colicin biology. Microbiology and Molecular biology Reviews, March. 2007; 71: 158-229. (http://mmbr.asm.org/cgi/ content/full/71/1/158)
11.
Jenssen H, Hamill P, Hancock R. Peptide Antimicrobal Agents. Clinical Microbiology. Oxford Press, London, 2011.
instructions for the authors All papers need to be sent to: Editorial board of the journal “Medical Archives (Med Arh)”, electronically over the web site www.scopemed.org. Every sent article gets its number, and author(s) will be notified if their paper is accepted and what is the number of paper. Every correspondence will use that number. The paper has to be typed on a standard format (A4), leaving left margins to be at least 3 cm. All materials, including tables and references, have to be typed double-spaced, so that one page has no more than 2000 alphanumerical characters (30 lines) and total number of used words must not to be more than 3,500. Presenting paper depends on its content, but usually it consists of a title page, summary, tex t references, legends for pictures and pictures. type your paper in MS Word and send it on a diskette or a CD-ROM, so that the editing of your paper will be easier. Title page. Every article has to have a title page with a title of no more than 10 words: name(s), last and first of the author(s), name of the institution the author(s) belongs to, abstract with maximum of 45 letters (including space), footnote(s) with acknowledgments, name of the first author or another person with whom correspondence will be maintained. Summary. The paper needs to contain structured summary, 200 words at the most. Summary needs to hold title, full name(s) and surname(s) of the author(s) and coauthor(s), work institution, and all essential facts of the work, introduction, formulation of problems, purpose of work, used methods, (with specific data, if possible) and basic facts. Summary must contain the re- view of underlined data, ideas and conclusions from text. Summary must have no quoted references. Four key words, at the most, need to be placed below the text. Central part of the article. Authentic papers contain these parts: introduction, goal, methods, results, discussion and conclusion. Introduction is brief and clear review of the problem. Methods are shown, so that interested reader is able to repeat described research. Known methods don’t need to be identified, they are cited (referenced). If drugs are listed, their generic name is used, (brand name can be written in brackets). Results need to be shown clearly and
Med Arh. 2014 Jun; 68(3): 167-169
logically, and their significance must be proven by statistical analysis. In discussion, results are interpreted and compared to the existing and previously published findings in the same field. Conclusions have to give an answer to author ’s goals. References. Quoting references must be on a scale, in which they are really used. Quoting most recent literature is recommended. Only published articles, (or articles accepted for publishing), can be used as references. Not published observations and personal notifications need to be in text in brackets. Showing references must be as how they appear in the text. References cited in tables or pictures are also numbered according to the quoting order. All references should be compiled at the end of the article in the Vancouver style or pubMed style (i.c. www. scopemed.org). Statistical analysis. Tests used for statistical analysis need to be shown in text and in tables or pictures containing statistical analysis. Tables and pictures. Tables have to be numbered and shown by their order, so they can be understood without having to read the paper. Every column needs to have a title, every measuring unit (SI) has to be clearly marked (i.e. preferably in footnotes below the table, in Arabic numbers or symbols). Pictures also have to be numbered as they appear in the text. drawings need to be enclosed on a white or tracing paper, while black and white photos have to be printed on a radiant paper. Legends (e.g. next to pictures and photos), have to be written on a separate A4 format paper. All illustrations, (pictures, drawings, diagrams), have to be original, and on their backs contain, illustration number, first author ’s last name, abbreviated title of the paper and picture at the top. It is appreciated, if author marks the place for the table or picture. Use of abbreviations. Use of abbreviations have to be reduced to a minimum. Conventional units can be used without their definitions. Supplement. If paper contains original contribution to a statistical method or author believes, without quoting original computer program, that paper ’s value will be reduced. Editorial staff will consider possibility of
publishing mathematics /statistic analysis in extension. Important policies. Any practice of plagiarism will not be tolerated regarding submitted articles. Non-identifiable quoted parts of the articles from other authors are known act of plagiarism if it is not cited or referencing in appropriate places in the article. Advertent practice of plagiarism will abort reviewing process or article submission. Author(s) may suggest or exclude peer-re-viewers for their articles but Editorial Board has the right to reject their(s) opinions or suggestions according to copyright Assignment form signed by authors before reviewing process. Authors must respect guidelines and rules of IcMjE, WAME, cOpE, E A SE, linked on www.avicenapublisher.org. Authorship. All individuals listed as authors should qualify for authorship and should have participated sufficiently in the work to take public responsibility for appropriate portions of the content and follow the next conditions: a) substantial contributions to the conceptions and design, acquisition of data, or anal- lysis and interpretation of data; b) drafting the article or revising it critically for important intellectual content; c) final approval of the version to be published (all co-authors must sign copyright Assignment form downloaded from www.avicenapublisher.org). All other contributors to the article’s subject who does not qualify for authorship should be listed in acknowledgement section. for all relevant information about authorship follow IcMjE guidelines. Conflict of interest. All authors must make a formal statement at the time of submission indicating any potential conflict of interest that might constitute an embarrassment to any of the authors if it were not to be declared and were to emerge after publication. Such conflict of interest might include, but not limited to, share holding in or receipt of grant or consultancy free form a company whose product features in the submitted manuscript or which manufactures a competing product. All authors must submit a statement of conflict of Interest to be published at the end of their article (conflict of Interest: NONE DECLARED).
169
