Lesotho public health institutions
Prescribing patterns of antibiotics in Lesotho public health
institutions
M.K.B. Adorka
Thesis submitted for the degree Doctor of Philosophy in
Pharmacy Practice at the Potchefstroom Campus of the
North-West University.
Promoter:
Prof J.H.P. Serfontein
Co-Promoter:
Prof M.S. Lubbe
Co-Promoter:
Prof A.G.S. Gous
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Acknowledgements
God Almighty takes the glory for the initiation and completion of this work. He is indeed a faithful God whose promises never fail.
My foremost gratitude for this work goes to the following persons at the North-West University for their various contributions in the conduct of this research and support of my efforts in compiling this thesis.
• My promoters, Professors J.H.P. Serfontein, M. S. Lubbe for their academic guidance. • Prof H.S. Steyn of the Statistics ConSUltation Services and here again to Prof Lubbe for the
significant role they played in the analysis of the research data.
• The entire staff of the Pharmacy Practice Department for their moral support. mention here particularly Ms A. Bekker and Mr W.D Basson, for their technical assistance.
• I\!1s M.M. Terblanche for proof reading and upgrading the grammatical use of the language for this 800 page thesis.
Sources of financing the collection and electronic capture of data for this research came from the National University of Lesotho and the Niche Area Medicine Usage of South Africa. express my sincere gratitude to these institutions.
My appreciation and thanks also go to the following at the National University of Lesotho.
• To former Vice and Pro-vice Chancellors, Professors M. M. Sejanamane and T. M. Makatjane for their personal support as I got on this project.
• To Mr S. Amaka of the English Language Department of the Faculty of Humanities for his assistance in editing portions of the thesis
• To Mr M. Ntlama, the manager of the Stationery and Printing department, the Bursar Mr J.J. Sekoere and Mr Mugomeri of the Faculty of Health Sciences, for the various ways in which they assisted me in printing and binding copies of this thesis.
• To Prof P. O. Odonkor, Dean of the Faculty of Health Sciences, for his support, encouragement and guidance as I pursued this programme
• To Dr T. Makoa and the entire staff of the Faculty of Health Sciences for their support and encouragement.
• To all students of the Bachelor of Pharmacy Honours degree programme of the National University of Lesotho who willingly assisted me in the field collection, summarization and I
and the diverse ways in which they assisted me in organising the research data for analysis.
The Ministry of Health & Social Welfare lent me a major support as I undertook this project. I extend in this regard my profound gratitude to the following:
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To the former Director General of Health Services (DGHS) of the Ministry, Dr H. M. Morosi, for granting me the permission and encouraging me to conduct this research. The importance he attached to this work and its potential benefit to the health delivery system of Lesotho greatly motivated me to carry it out this study to its logical conclusion.+
To J. Nkonyana, Head of the Epidemiological Unit of this Ministry for helping me develop questionnaires for Phase III of this research.+
To the Medical Superintendent of the Queen Elizabeth II and the District Medical OfficersCDMOs) of the Motebang, Berea, Maluti and Scott Hospitals for granting me the permission to conduct this research in their hospitals.
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The Pharmacy and Medical Laboratory staffs of the study site hospitals for the assistance and cooperation they gave me in collecting data for this study.I further express my utmost gratitude to the following relatives of mine.
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To my loving wife, Lineo Mpela-Adorka for her unflinching support.+
To my wonderful children, Neko, Anyo, Esenam, Seyram and Selorm. The validation of who I am as a father to them and an icon of a human they look up to and emulate in life, placed a value on me. This value gave me the self esteem and motivation I needed for this work.+
To Dr John Wayem of the UNDP, Dr C. K & Dr (Mrs) Hoedoafia, Mssrs Henry Akutsa and Justice Y. Adzimah, for joining hands in removing emotional stresses and financial hiccups that severally threatened my focus as I pursued this programme.+
To Bishop James Dinu, in his capacity as a mathematician and educator in mathematics, for validating mathematical concepts I used in developing formulae for quantifying the characteristics of antibiotics that are considered in principle in the selection of these agents in the empiric treatment of infections.SUMMARY
KEY WORDS: Principles, antibiotic prescribing, influencing factors, antibiotic prescriptions, appropriateness, bacterial pathogens, antibiotic sensitivity patterns, antibiotic selection, empiric treatment of infections.
In Lesotho, a relatively poor country, empiric use of antibiotics, rather unsupported by sufficient knowledge of the sensitivities of bacterial pathogens to the agents, is by observation a mainstay of treating infections. Such manners of antibiotic prescribing were witnessed as would not altogether be conducive to appropriate prescribing, contrary to an urge of the World Health Organisation for countries to use antibiotics appropriately as a strategy for curbing bacterial pathogen antibiotic resistance development. The purpose of this study, was to investigate, inter alia, the extent to which antibiotics are appropriately prescribed and to make available baseline information that would assist in the formulation of relevant policies on the judicious use of the drugs.
Conducted in three phases and in accordance with its set objective, the study generally investigated the extent to which antibiotics were appropriately prescribed and the impact of antibiotic prescribing on treatment outcomes and related costs identified bacterial pathogens commonly associated with diagnosed infections, made predictions of the clinical effectiveness of antibiotic prescribing for diagnosed infections, identified factors that principally would influence prescribers' manner of prescribing antibiotics and developed procedures to enhance the appropriate selection of antibiotics in the empiric treatment of infections.
A novel method based on prescribers' adherence to principles of antibiotic prescribing was developed and used in asseSSing the appropriateness of antibiotic prescriptions. Data on antibiotic prescriptions were collected prospectively from inpatient and outpatient departments of selected hospitals. Data on bacterial pathogen sensitivities to formulary antibiotics, similarly, were collected retrospectively from records of culture sensitivity test results as kept by microbiology laboratories of study site hospitals. Analysis of data was done to show associations of pathogens with diagnosed infections and their sensitivity patterns to formulary antibiotics. A formula for quantifying the activity and cost characteristics of antibiotics was developed and used in selecting antibiotics most appropriate in the empiric treatment of given infections. A structured questionnaire survey that targeted prescribers at health service areas of
antibiotic prescribing was also carried out.
Results of the study showed that antibiotics were most often prescribed inappropriately in inpatient departments, as compared to outpatient departments. Appropriate antibiotic prescribing in inpatient departments appear to have a positive impact on treatment outcomes and costs of antibiotic treatment. Ampicillin and metronidazole and ampicillin and co-trimoxazole were observed as the first and second most frequently prescribed antibacterial agents in inpatient and outpatient departments respectively. Pathogens predominantly associated with given infections in inpatient departments of study site hospitals were identified as Staphylococcus aureus for lower respiratory tract, eye, ear, and skin and soft tissue infections; Streptococcus pneumoniae for meningitis; Escherichia coli for ascites and urinary tract infections; and Proteus spp for septicaemia. Between January 2000 and December 2005, substantial increases in resistance to cloxacillin, ampicillin, co-trimoxazole and cefotaxime were noticed for Staphylococcus aureus. Similar increases in the case of co-trimoxazole were observed for E. coli and Klebsiella spp. Among gram-positive cocci, ampicillin demonstrated the highest activities against S. pneumoniae and S. pyogenes. Activity of gentamicin against gram negative bacilli was largely preserved despite the high rate of prescribing the antibiotic in inpatient departments. A large majority of prescribers prescribe antibiotics commonly whenever they are not sure of the aetiologies of diagnosed cases. A majority of prescribers composed of all qualification categories also lack adequate knowledge in bacteriology and principles of antibiotic prescribing. Shortcomings exist in mechanisms of disseminating results of tests on microbial examination of specimens to prescribers.
In line with findings of this study, it is recommended that the Ministry of Health and Social Welfare institute measures aimed at improving antibiotic prescribing in the country's health institutions. It is particularly recommended that policies be formulated with regard to appropriate prescribing of antibiotics; development of user friendly algorithms of infection diagnosis and treatment; improvement of functional capabilities of microbiology laboratories
vis
avis
the institution of effective information network systems for information dissemination on patterns of microbial resistance to commonly used antibacterial agents; and also the education of prescribers on antibiotic prescribing.OPSOMMING
SLEUTELWOORDE: Beginsels, voorskryf van antibiotika, bernvloedende faktore,
antibiotikavoorskrifte, geskiktheid, bakteriele patogene, sensitiwiteitspatrone van plaaslike antibiotika, keuse van 'n antibiotikum, empiriese behandeling van infeksies
In Lesotho,
'n
relatief arm land, is die empiriese gebruik van antibiotika wat meesal nie deur voldoende kennis van die sensitiwiteit van bakteriele patogene vir die middels ondersteun word nie, na waarneming die steunpilaar vir behandeling van infeksies, Dit is waargeneem dat sodanige gebruik van antibiotika nie die korrekte voorskryf daarvan bevorder nie, in teenstelling met die oproep van die Wereldgesondheidsorganisasie dat lande antibiotika oordeelkundig moet gebruik as 'n strategie am die ontwikkeling van weerstand van bakteriele patogene teen antibiotika te be perk. Die doel van hierdie studie was onder meer am die mate waartoe antibiotika toepaslik voorgeskryf word, te ondersoek en am basislyninligting beskikbaar te stel wat sal help am relevante beleid vir die oordeelkundige gebruik van hierdie medisyne te formuleer.Die studie is volgens die gestelde doel in drie fases gedoen, waarin die mate waartoe antibiotika toepaslik voorgeskryf is en die impak wat die voorskryf van antibiotika op die uitkomste van behandeling en verwante koste het, ondersoek is, waarin bakteriele patogene wat algemeen in gediagnoseerde infeksies voorkom, ge'identifiseer is, waarin voorspellings van die kliniese effektiwiteit van die voorskryf van antibiotika vir gediagnoseerde infeksies gemaak is, waarin faktore geYdentifiseer is wat die voorskrywer se manier vir die voorskryf van antibiotika bernvloed en waarin prosedures am die seleksie van geskikte antibiotika vir die empiriese behandeling van infeksies ontwikkel is.
'n Nuwe metode, gebaseer op die nakoming van die beginsels vir die voorskryf van antibiotika deur die voorskrywer, is ontwikkel en gebruik am die geskiktheid van voorskrifte vir antibiotika te beoordeel. Data van voorskrifte vir antibiotika is van binne- en buitepasientafdelings van geselekteerde hospitale versamel. Data van die sensitiwiteit van bakteriele patogene vir antibiotika is soortgelyk retrospektief van die rekords van sensitiwiteitstoetse van die mikrobiologiese laboratoriums van die hospitale van die studie verkry. 'n Ontleding van die data is gedoen am die verband tussen patogene en gediagnoseerde infeksies en hulle sensitiwiteit teenoor antibiotika te toon, 'n Formule am die aktiwiteit en die koste van antibiotika te
behandeling van gegewe infeksies te kies. 'n Ondersoek met 'n gestruktureerde vraelys wat voorskrywers in areas van gesondheidsorg by die studiehospitale geteiken het en daarop gemik was om die faktore wat voorskrywers se manier vir die voorskryf van antibiotika te bepaal, is ook gedoen.
Resultate van die studie het getoon dat antibiotika meer dikwels in binnepasientafdelings as in buitepasientafdelings ontoepaslik voorgeskryf word, Oit Iyk asof die toepaslike voorskryf van antibiotika in binnepasientafdelings 'n positiewe invloed op die uitkomste en die koste van behandeling met antibiotika het. Oit is opgemerk dat ampisillien en metronidasool, en ampisillien en kotrimoksasool die antibakteriele middels is wat die meeste en tweede meeste in die binne- en buitepasientafdelings onderskeidelik voorgeskryf word. Patogene wat hoofsaaklik met gegewe infeksies in die binnepasientafdelings van die studiehospitale gepaardgaan, is as
Staphylococcus aureus vir infeksies van die onderste lugweg, oe, ore, vel en sagte weefsel,
Streptococcus pneumoniae vir meningitis, Escherichia coli vir askites en urienweginfeksies en
Proteus spp vir septisemie ge'identifiseer. Tussen Januarie 2000 en Oesember 2005 is beduidende toename in die weerstand van Staphylococcus aureus teen kloksasillien, ampisillien, kotrimoksasool en kefotaksiem waargeneem. Soortgelyke toenames is in die geval van E coli en Klebsiella spp. teen kotrimoksasool waargeneem. Van die gram-positiewe kokke het ampisillien die sterkste aktiwiteit teen S. pneumoniae en S. pyogenes getoon. Aktiwiteit van gentamisien teen gram-positiewe basille is grootliks behou ten spyte van die groot mate waartoe die antibiotikum in binnepasientafdelings voorgeskryf is. Die oorgrote meerderheid voorskrywers skryf antibiotika algemeen voor selfs al is hulle nie seker van die etiologie van gediagnoseerde gevalle nie. 'n Groot deel van voorskrywers van aile kategoriee wat kwalifikasies betref, het nie voldoende kennis van bakteriologie en die beginsels vir die voorskryf van antibiotika nie. Oaar is tekortkominge in die meganismes vir die verspreiding van toetsuitslae van mikrobiologiese ondersoeke van monsters aan voorskrywers.
Ooreenkomstig die bevindinge van hierdie studie word aanbeveel dat die minister van gesondheid en maatskaplike welsyn maatreels instel wat daarop gemik is om die voorskryf van antibiotika in die land se gesondheidsinrigtings te verbeter. Oit word veral aanbeveel dat beleid geformuleer word vir die toepaslike voorskryf van antibiotika, die ontwikkeling van gebruikersvriendelike algoritmes vir die diagnose en behandeling van infeksies, vir die
instel van effektiewe netwerkstelsels vir die verspreiding van inligting oor die patrone van mikrobiese weerstand teen antibakteriele middels wat algemeen gebruik word en ook vir die opvoeding van voorskrywers vir die voorskryf van antibiotika.
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Table of contents
TABLE
OF CONTENTS
Page
List of Tables ... .. ... ... ... ... ... ... ... ... xix
List of Figures ... ... ... ... ... ... xxviii
List of Appendices... ... ... ... ... ... ... ... ... xxxii
List of Abbreviations ... xxxv
List of Definitions... ... ... ... ... ... ... ... ... ... ... ... xxxviii
CHAPTER ONE - STUDY OVERVIEW 1 1.1 Introduction... ... ... ... 1
1.2 Background and problem statement... 1
1.2.1. Research questions... ... ... ... ... ... ... ... ... ... ... ... 7
1.3 Research objectives... ... ... ... ... 8
1.3.1 . General research objectives... 8
1.3.2 Specific research objectives... 8
1.3.2.1 Literature Review ... '" ... ... ... 9
1.3.1.2 Empiric research... ... ... ... 9
1.4 Research design and methodology... ... ... ... ... 11
1.4.1 Research type... ... ... 11 1.4.2 Study sites... ... ... 11 1.4.3 Research methodology... ... ... ... 12 1.4.4 Literature study ... ... 12 1.4.5 Empirical Study... ... ... ... ... ... ... ... 12 1.4.6 Data analysis... ... ... ... ... ... ... 14 1.4.7 Study samples... ... ... ... ... ... ... ... ... 14
1.4.7.1 Antibiotic prescription data - Phase I of empiric study ... '" ... 15
1.4.7.2 Culture sensitivity test result data - Phase II of empiric study... ... 15
1.4.7.3 Factors contributing to established pattems of antibiotic prescribing... 15
1.4.7.4 Inclusion and Exclusion Criteria ... ... ... ... ... ... 15
1.5 Results reporting... ... ... ... ... ... ... ... ... 16
1.6 Ethical permissions... ... ... ... ... 16
1.7 Chapter divisions... ... ... ... ... ... ... 16
17
CHAPTER
Two -
BACTERIAL PATHOGENS, ANTIBIOTICS, PRINCIPLES OF ANTIBIOTIC PRESCRIBING2.1 Bacterial pathogens: Morphological characteristics, classification and mechanisms
of pathogenesis ... 17
2.1.1 Cell wall structure and staining characteristics ... 18
2.1.2 Morphological classifications ... 19
2.1.2.1 Gram-positive bacteria ... ... ... ... ... 20
2.1.2.2 Gram-negative bacteria... ... ... ... ... ... 20
2.1.3 Mechanisms of bacterial pathogenesis... 24
2.1.4 Gram-positive bacterial pathogens: Pathogenesis, antibiotic susceptibilities, associated infections and recommended treatments. ... 39
2.1.4.1 Streptococcus spp and Enterococcus spp... ... 39
2.1.4.2 Staphylococcus spp ... ... 62
2.1.4.3 Clostridium spp. ... 69
2.1.4.4 Corynebacterium spp ... ... 74
2.1.5 Gram-negative bacterial pathogens: Pathogenesis, antibiotic susceptibilities, associated infections and recommended treatments... ... ... 76
2.1.5.1 Gram-negative cocci... ... ... ... ... ... ... ... ... ... . ... ... 76
2.1.5.1.1 Neisseria spp ... ... ... ... .... ... 76
2.1.5.1.2 Moraxella spp. ... ... 85
2.1.5.2 Gram-negative bacilli ... 87
2.1.5.2.1 Escherichia coli ... ... ... ... 88
2.1.5.2.1.1 Intestinal pathogenic coli.. ... 89
2.1.5.2.1.2 Extra intestinal pathogenic coli ... 91
2.1.5.2.2 Klebsiella spp ... ... ... ... 96 2.1.5.2.3 Proteus spp ... ... ... 100 2.1.5.2.4 Salmonella spp ... ... ... ... 102 2.1.5.2.5 Shigella spp ... ... ... 108 2.1.5.2.6 Haemophifus spp (Parvobacteria) ... ... 111 2.1.5.2.7 Pseudomonas aeruginosa ... ... ... 115
2,2 Mechanisms of bacterial resistance development to antibiotics... .. ... 127
2.2.1 Efflux pump systems in bacterial pathogens... ... ... 127
Modification of antibiotic targets and reprogramming of biosynthetic pathway '" ... ... ... . .. ... . . .. . .. . .. . . .. ... . .. . . .. . . . .. . .. . . ... . . 129
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2.3 Exploiting mechanisms of pathogen antibiotic resistance in the development
of new antibiotics... ... ... ... ... ... ... 132
2.3.1 Antibiotic discoveries based on efflux technologies ... ... ... ... 132
2.3.2 !3-lactam antibiotic/!3-lactamase-inhibitor combinations... ... ... ... .... 134
2.4 Antibiotics: Classification and characteristics, mechanisms of actions and clinical applications ... ... 135
2.5 Appropriate antibiotic prescribing: Definition and principles... ... ... ... 185
2.6 Assessing appropriateness of antibiotic prescriptions: Merits and demerits of methods... ... ... ... ... ... 193
2.7 Chapter summary ... ... ... ... ... ... ... ... 201
CHAPTER THREE - RESEARCH METHODOLOGY 202 3.1 Introduction... ... ... ... ... ... 2.2 3.2 Training of Fieldworkers ... ... ... ... ... ... .. ... 204
3.3 Empiric research Phase I: Antibiotic prescribing pattern study in inpatient and outpatient departments. ... ... ... ... ... ... ... ... 204
3.3.1 Research objectives... ... 204
3.3.2 Study site selection ... 207
3.3.3 Developing data collection tools and procedures of data collection and prescription categorisation.. ... ... 207
3.3.3.1 Developing data collection tools... ... ... ... ... 207
3.3.3.2 Sources of data and procedures of data collection... ... 207
3.3.3.3 Classification of antibiotic prescriptions ... ... 208
3.3.4 Criteria developmentfor prescription assessment. ... 209
3.3.4.1 Rationale for criteria development ... ... ... ... 212
3.3.5 Antibiotic treatment outcomes and cost determinations... 218
3.3.6 Data analysis: Research Phase I ... ... ... ... 220
3.3.6.1 Analysis of inpatient antibiotic prescription data ... ... 220
3.3.6.2 Analysis of outpatient antibiotic prescription data... ... ... 231
3.4 Empiric research Phase II: Antibiotic prescribing pattern study in inpatient and outpatient departments ... '" ... ... ... ... ... ... ... ... ... 232
3.4.1 Research objectives ... ... 232
3.4.3 Analysis of culture sensitivity results data ... 234
3.5 Procedures of selecting antibiotics in empiric treatment of infections ... ... 235
3.5.1 Developing formula for calculating percentage overall activity (POA) of given antibiotics ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... 236
3.5.2 Developing method for selecting an antibiotic of choice in treating a given infection. ... ... ... 238
3.5.3 Use of percentage overall activity characteristics and costs of antibiotics in the rational selection of the drugs... 242
3.6 Empirical research Phase III: Investigating factors influencing patterns of antibiotic prescribing in public health institutions in Lesotho. ... 244
3.6.1 Research objective ... 244
3.6.2 Study population ... ... ... 245
3.6.3 Method of data collection ... ... ... ... ... ... 245
3.6.4 Structuring of questionnaires, rationale of question formulation and purposes of questions... ... 248
3.6.5 Scaling of questionnaires ... ... ... ... 252
3.6.6 Questionnaire administration... ... 252
3.6.7 Validation of data ... ... ... 253
3.6.8 Data analysis of Phase III ... ... ... ... ... ... ... ... 253
3.7 Statistical methodology... 262
3.8 Chapter Summary ... ... 264
CHAPTER FOUR - RESULTS AND DISCUSSIONS 265 4.1 Empirical research Phase I Appropriateness assessment of inpatient and outpatient antibiotic prescriptions... ... ... 266
4.1.1 Assessment of inpatient antibiotic prescriptions ... 266
4.1.1.1 Prescription categorisation and determination of percentage frequency distribution of prescription categories by study sites and ward types... 267
4.1.1.1.1 Results ... 267
4.1.1.1 Results Evaluation and Discussion ... ... 277 4.1.1.2 Determining the impact of appropriate or inappropriate prescribing of
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4.1.1.2.1 Results... ... ... ... ... ... ... 283
4.1.1.2.2 Results Evaluation and Discussion ... ... ... ... 297
4.1.1.3 Determining patterns and effects on treatment outcomes of multiple antibiotic prescribing in wards. ... ... ... ... 310
4.1.1.3.1 Results ... 310
4.1.1.3.2 Results Evaluation and Discussion... ... 319
4.1.1.4 Determining leading infections and antibiotics most commonly prescribed for them at study site inpatient departments... ... ... ... ... 323
4.1.1.4 .1 Results... ... ... ... ... 325
4.1.1.4.2 Results Evaluation and Discussion ... 340
4.1.1.5 Determining patterns of antibiotic prescribing in and patients' responses to post-surgical antibiotic prophylaxis... 355
4.1.1.5.1 Results ... ... ... 355
4.1.1.5.2 Results Evaluation and Discussion ... ... ... 358
4.1.2 Outpatient antibiotic prescription assessment... ... .... 364
4.1.2.1 Outpatient antibiotic prescribing patterns according to prescription categories, study sites and prescriber qualifications ... 364
4.1.2.1.1 Results ... ... 364
4.1.2.1.2 Results Evaluation and Discussion ... 372
4.1.2.2 The impact of appropriateness of antibiotic prescribing on average costs of antibiotic prescriptions... ... ... ... .... 376
4.1.2.2.1 Results ... ... ... ... ... 376
4.1.2.2.2 Results Evaluation and Discussion ... ... ... 379
4.1.2.3 Multiple antibiotic prescribing and the impact of antibiotic stock unavailability on prescribers' choice of antibiotics ... 380
4.1.2.3.1 Results... ... ... ... ... 381
4.1.2.3.2 Results Evaluation and Discussion ... 383
4.1.2.4 Determining the extent to which prescribers establish need for antibiotic use or presence of infections prior to prescribing antibiotics... 395
4.1.2.4.1 Results... ... ... 395
4.1.2.4.2 Results Evaluations and Discussion... ... ... 398 4.1.2.5 Determining leading infections and antibiotics most commonly prescribed
for their treatment ... 402
4.1.2.5.1 Results... ... ... ... ... ... 402
4.1.2.5.2 Results Evaluation and Discussion ... ... ... ... ... ... ... ... 418
4.1.2.6 Summary: Research Phase I ... ... ... 449
4. 2 Empirical Research Phase II: Bacterial pathogens - Associations with infections and antibiotic sensitivity patterns ... 450
4.2.1 Bacterial pathogens commonly isolated at study sites ... ... ... ... ... ... 450
4.2.1.1 Results ..., ... ... ... ... 451
4.2.1.2 Results Evaluation and Discussion ... 458
4.2.2 Bacterial pathogen associations with specimens... ... ... ... .... 463
4.2.2.1 Results ... ... ... 463
4.2.2.2 Results Evaluation and Discussion ... ... ... 479
4.2.3 Sensitivities and variations in yearly percentage resistances of bacteria pathogens to formulary antibiotics - January 2000 - Dec 2005 ... ... ... ... .... 501
4.2.3.1 Bacterial isolates and their reported patterns of sensitivities to formulary Antibiotics... ... ... 501
4.2.3.1.1 Results... ... ... 501
4.2.3.1 Results Evaluation and Discussion... ... ... 509
4.2.3.2 Variations in percentage yearly resistances of bacterial isolates to formulary antibiotics ... 527
4.2.3.2.1 Results... ... ... ... ... ... ... 528
4.2.3.2.2 Results Evaluation and Discussion... 562
4.2.4 Antibiotic selection for empiric treatment of infections: Practical use of percentage overall activity (POA) and antibiotic selection factors (ASF) in the selection of antibiotics ... ... ... ... ... 581
4.2.4.1 Results ... ... ... ... ... 581
4.2.4.2. Results Evaluation and Discussion... ... 587
4.2.5 Summary: Research phase II ... ... ... ... ... ... ... ... 594
4.3 Empirical Research Phase III: Factors influencing antibiotic prescribing patterns in Lesotho ... 595
4.3.1 Questionnaire response rate and demographic data analysis... ... ... 595
4.3.1.1 Results ... ... 595
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influence prescribers' decisions to prescribe antibiotics ... ... ... ... ... 613
4.3.2.1 Results... ... ... ... ... 613
4.3.2.2 Results Evaluation and Discussion... 618
4.3.3 Determining the extent to which respondents prescribe antibiotics only after positively establishing the presence of infections... ... 627
4.3.3.1 Results... ... ... ... ... ... ... ... ... 627
4.3.3.2 Results Evaluation and Discussion ... ... 633
4.3.4 Determining the extent to which respondents adhere to principles of rational prescribing of antibiotics in inpatient settings... ... ... ... 638
4.3.4.1 Results... ... ... ... ... ... 638
4.3.4.2 Results Evaluation and Discussion... ... ... 646
4.3.5 Assessing prescribers' knowledge in principles of antibiotic selection and prescribing ... ... 652
4.3.5.1 Results... 653
4.3.5.2 Results Evaluation and Discussion... ... 675
4.3.6 Determining the extent to which antibiotic stock unavailability limit respondents' ability to select antibiotics of choice ... 698
4.3.6.1 Results... 698
4.3.6.2 Results Evaluation and Discussions ... 704
4.3.7 Investigating reasons for prescribers' non-request for information on the morphological characteristics of target bacterial pathogens as basis for empiric antibiotic prescribing ... 709
4.3.7.1 Results ... 710
4.3.7.2 Results Evaluation and Discussion ... 713
4.3.8 Determining the extent of respondents' need for antibiotic prescription guidelines and refresher courses ... 717
4.3.8.1 Results ... ... ... ... ... ... ... 717
4.3.8.2 Results Evaluation and Discussion ... 719
4.4 Limitations of the study... ... 724
CHAPTER FIVE - CONCLUSIONS AND RECOMMENDATIONS 728 5.1 Inferences on assessment of inpatient prescriptions ... 728
5.1.1 The extent of appropriate prescribing of antibiotics at study site inpatient
departments. ... 729 5.1.2 Impacts of appropriateness of antibiotic prescribing on treatment outcomes .... 729 5.1.3 Patterns and impacts of multiple antibiotic prescribing on treatment
outcomes... ... ... 730 5.1.4 Leading infections and antibiotics most commonly prescribed for their
treatment at study site inpatient departments... ... ... ... ... 730 5.1.5 Effectiveness predictions of antibiotic treatments in inpatient department of
study sites ... 733 5.1.6 Antibiotic prescribing in post surgical wound treatment... ... ... ... 733 5.2 Inferences on assessment of outpatient prescriptions ... ... 734
5.2.1 Prescriber qualifications involved in prescribing antibiotics appropriately in
outpatient departments... ... ... ... ... ... ... ... ... ... ... 735 5.2.2 Patterns and the extent of appropriate prescribing of antibiotics in outpatient
departments of study sites... ... ... ... ... ... ... ... ... 735 5.2.3 Comparative abilities of prescriber classification groups in writing prescriptions
of defined prescription categories in outpatient departments ... ... 735 5.2.4 Impacts of appropriateness of antibiotic prescribing on mean costs of antibiotic
prescriptions in outpatient departments... ... ... ... 736 5.2.5 Antibiotic wastage resulting from prescribing for unjustified clinical reasons ... 736 5.2.6 The extent and effectiveness predictions of single antibiotic prescribing in
treating infections in outpatient departments... ... 737 5.2.7 Impacts of antibiotic stock unavailability on prescribers' choice of antibiotics
in outpatient departments... ... 738 5.2.8 The extent to which prescribers establish patients' need for antibiotics before
prescribing the drugs... ... ... ... ... ... ... ... 738 5.2.9 Accuracy evaluations of prescriber diagnosed infections and its effects on
appropriateness of antibiotic prescribing in outpatient departments... ... 739 10 Leading infections and their patterns of prevalence at study site outpatient
departments ... 739 11 Patterns of antibiotic prescribing in the treatment of diagnosed infections
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5.2.12 Pathogen associations with and effectiveness predictions of prescribers' choices
of antibiotics in the treatment of diagnosed infections ... 740
5.3 Inferences on bacterial pathogen sensitivity data analysis ... ... ... ... ... ... ... 744
5.3.1 Bacterial pathogens and the extent of their isolations at study sites ... 744
5.3.2 Bacterial pathogen associations with diagnosed infections ... ... ... ... .... ... 745
5.3.3 Summary conclusions on diagnosed infections and associated pathogens for coverage in empiric antibiotic treatment ... , ... ... ... 746
5.3.4 Patterns of bacterial pathogen sensitivities to formulary antibiotics ... 748
5.3.5 Variations in percentage yearly resistances of bacterial isolates to formulary antibiotics over a six-year period from January 2000 to December 2005 ... 751
5.3.6 Antibiotic selection for empiric treatment of infections ... ... 753
5.4 Inferences on factors attributing to patterns of antibiotic prescribing ... ... ... 754
5.4.1 Percentage frequency of distribution of respondents according to their demographic data ... ... 754
5.4.2 Availabllity and capacities of microbiology laboratories at respondents' practice sites... ... ... 755
5.4.3 Influence of patient and prescriber related factors on prescribers' decisions to prescribe antibiotics... ... ... 755
5.4.4 Antibiotic prescribing in outpatient departments on the basis of positive establishment of presence of infections... ... ... ... ... ... ... 757
5.4.5 The extent of prescribers' adherence to principles of rational prescribing of antibiotics in inpatient settings... ... ... 757
5.4.6 Assessment of prescribers' knowledge in principles of antibiotic selection and prescribing ... 758
5.4.7 Costs of antibiotics and pathogen antibiotic sensitivity patterns as factors influencing respondents' choices of antibiotics ... ... 759
5.4.8 Antibiotic stock unavailability as a factor influencing respondents' ability to select antibiotics of choice... ... ... ... ... 760
5.4.9 Factors contributing to prescribers' non-adherence to the principle of requesting for microscopic identification of infecting pathogens before empiric antibiotic therapy initiation ... ... 760
5.5 Limitations in the use of study results ... ... ... 761
5.6 Recommendations... ... ... 762
5.6.1 Improving culture sensitivity data quality for future studies ... ... ... ... ... ... 762
5.6.2 Improving procedures of infection diagnosis and antibiotic prescribing for quality management of patients for infections... ... ... ... ... 763
5.6.3 Changes of antibiotic prescription protocols ... :... 763
5.6.4 Addressing problems contributing to inappropriate antibiotic prescribing at study sites. ... 765
5.6.5 Building capacity for the appropriate prescribing and use of antibiotics: Suggested roles of pharmacists in the implementation of research recommendations... ... ... ... ... ... ... 765
5.7 Recommendation for further studies ... 766
5.8 Chapter summary... ... 767
5.8 REFERENCES... ... ... 768
LIST OF TABLES Page Table 1.1 Table 1.2 Table 1.3 Table 2.1 Table Table 2.3 Table 2.4 Table 2.5 Table 2.6 Table 2.7 Table 2.8 Table 2.9 Table 3.1 Table 3.2 Table 3.3 Table 3.4 Table 3.5 Table 3.6 Table 3.7 Table 3.8 Table 3.9 Table 3.10 Table 4.1.1
Total outpatient department (OPD) attendance by disease classification for aJl hospitals in Lesotho... 5 Queen Elizabeth II Hospital annual drug consumption data (1999-2002) ... 7 Data collection tools and guidelines: Their purposes and appendix references 13 Table 2.1 Terms used to describe adherence factors in host-parasite interactions 28 Group definitions and epidemiology of streptococci ... 41 Features of Pneumonia caused by different bacteria... ... ... ... 45 Recommended treatment for Gonococcal Infections: 2002 Guidelines of the
Center for Disease Control and Prevention... 83 Antibiotics used in empirical therapy of bacterial meningitis and focal
CNS infections... ... ... ... ... ... ... ... ... ... ... 84 Treatment regimens for bacterial urinary tract infections... ... ... ... ... ... 95 Recommended antimicrobial therapy for selected infections due to
Pseudomonas aeruginosa ... 125 Classifications and mechanisms of action of antibiotics... ... 136 Antibiotics: Their spectra of activities, clinical applications and associated adverse effects ... 158 Summary of prescription category definitions .. ... 210 Criteria for determining appropriateness of antibiotic prescriptions for
inpatients... ... ... ... ... ... ... ... ... 211 Criteria for determining appropriateness of antibiotic prescriptions for
outpatients... ... ... ... ... 211 Criteria combinations and their indications: Inpatient data... 221 Criteria combinations and their indications: Outpatient data... ... 222 Inpatient prescription rationality categorization... 223 Outpatient prescription rationality categorization... ... ... 224 Example of Table showing pathogen frequency and sensitivity values for
formula derivation... ... ... ... ... 236 Example of Table showing calculated probabilities and POAs of antibiotics
against isolated pathogens... 238 Example of Table showing calculated antibiotic selection factors (ASFs) ... 242 Percentage frequency distribution 'of antibiotic prescriptions by categories
Table 4.1.2 Percentage frequency distribution of prescriptions by categories and according to study site hospitals... 272 Table 4.1.3 Percentage frequency distribution of prescription categories by ward types ... 276 Table 4.1.4.1 Percentage frequency distribution of Category A 1 prescriptions by treatment
outcomes and according to study sites... ... 284 Table 4.1.4.2 Percentage frequency distribution of Category A2 prescriptions by treatment
outcomes and according to study sites... ... ... ... 284 Table 4.1.4.3 Percentage frequency distribution of Category B prescriptions by treatment
outcomes and according to study sites ... 284 Table 4.1.4.4 Percentage frequency distribution of Category C prescriptions by treatment
outcomes and according to study sites ... '" 284 Table 4.1.5 Percentage frequencies of antibiotic treatment response indicators and
calculated therapeutic success rates by prescription categories... 287 Table 4.1.6 Percentage frequencies of number of days of patients in hospital according
prescription categories... ... ... ... ... ... ... ... ... 287 Table 4.1.7 Frequencies of prescription categories according to diagnoses for which they were
prescribed ... '" ... ... ... ... 288 Table 4.1.8 Effect sizes for differences between means of number of days of hospitalisation
for patient groups diagnosed and not diagnosed for given infections
(excluding deaths) ... ... ... ... ... ... ... ... ... 289 Table 4.1.9 Percentage frequencies and mean days of hospitalisation of patients treated
with antibiotic prescription categories A 1! A2 and B for diagnosed infections. ... 290 Table 4.1.10 Percentage frequency distributions of prescriptions by category definitions and
according to study sites and costs of prescriptions... 294 Table 4.1.11 Costs of antibiotic treatment by prescription categories... ... 295 Table 4.1.12 Percentage frequency distribution of prescriptions by study site and according
to number of prescribed antibiotics ... ... ... ... ... ... ... ... ... 311 Table 4.1.13 Percentage frequency distribution of prescriptions by categories and according
to number of prescribed antibiotics per prescription ... ... ... ... 314 Table 4.1.14.1 Treatment success rates of patients in prescription category groupings
receiving given number of antibiotics: Prescription category A 1 ... 318 Table 4.1.14.2 Treatment success rates of patients in prescription category groupings
List of Tables
Table 4.1.14.3 Treatment success rates of patients in prescription category groupings
receiving given number of antibiotics: Prescription category B ... 318 Table 4.1.14.4 Treatment success rates of patients in prescription category groupings
receiving given number of antibiotics: Prescription category C ... 318 Table 4.1.15 List of prescriber indicated diagnoses or symptoms indicating presence of
infections or conditions indicating potential sources for infections at various
body sites for which antibiotics were prescribed... 326 Table 4.1.16 List of prescriber's indicated diagnoses or symptoms for which antibiotics were
either prescribed alone or in combination with symptoms or diagnosed cases
of infections... ... ... ... ... ... 327 Table 4.1.17 Percentage frequency distribution of diagnosis and treatment of infection
types among inpatients at study sites... ... 329 Table 4.1.18 Percentage frequency distribution of prescribed antibiotics according to
clinical conditions... ... ... ... ... ... ... ... ... ... 335 Table 4.1.19 Most commonly prescribed antibiotics for diagnosed infection types and
common bacterial pathogens associated with them... ... ... ... ... 349 Table 4.1.20 Frequencies of surgical wound types treated prophylactically... .... ... ... ... ... .... 356 TableA.1.21 Percentage frequency distribution of prescribed antibiotics/antibiotic
combination according to surgical wound types... ... ... ... 356 Table 4.1.22 Percentage frequency distributions of patients' responses to post-surgical
antibiotic prophylaxis by surgical wound types ... ... 357 Table 4.1.23 Number of prescriptions according to study site and qualifications of
prescribers... ... ... ... ... ... 365 Table 4.1.24 Prescription categories according to study sites and prescriber qualifications .... 370 Table 4.1.25 Frequency distribution of prescriptions by categories and costs according to
study sites... ... ... ... ... ... 377 Table 4.1.26 Frequencies of numbers of prescribed antibiotics per prescription by study
sites ... ... ... ... ... ... ... ... 382 Table 4.1.27 Relative frequencies of prescriptions by study sites and according to ranks of
prescribers' choices of dispensed antibiotics and basis of choices being
unavailability of 15t choice prescribed antibiotics ... 382 Table 4.1.28 Percentage frequency distribution of prescriptions by study site and according
to prescribers' use of antibiotic need assessment criteria in determining patients' need for antibiotics... ... ... ... ... ... 397
Table 4.1.29 Frequencies of use of diagnostic terms, symptoms and symptom complexes
in categorising respiratory tract infections in outpatient departments... 404 Table 4.1.30(a) Frequencies of use of diagnostic terms, symptoms and symptom
complexes in categorising urinary tract infections in outpatient
departments... ... ... ... ... ... 405 Table: 4.1.30 (b) Frequencies of use of diagnostic terms and symptoms in categorising
urinary tract urinary tract infections in outpatient departments... 406 Table 4.1.31 Frequencies of use of diagnostic terms, symptoms and symptom complexes in
categorising gastrointestinal infections in outpatient departments. ... 407 Table: 4.1.32 Frequencies of use of diagnostic terms, symptoms and symptom complexes in
categorising skin and soft tissue infections in outpatient departments... ... 407 Table 4.1.33 Frequencies of diagnosis and treatment of infection types among outpatients at
study sites ... 408 Table 4.1.34 Percentage frequency distribution of prescribed antibiotics according to clinical
conditions ... ... ... ... ... ... ... 415 Table 4.1 Calculated ratios of percentage frequencies of category A 1 and category A2
prescription; and also of the total percentage frequencies of SSI and GUTI on
one hand and RTI on the other ... 426 Table 4.1.36 Examples of appropriately written prescriptions with indicated diagnosis/
symptoms for which they were written... ... ... 427 Table 4.2.1 Frequencies of bacteria pathogen isolation according to study sites from
Jan 2000 to June 2006 ... ... ... ... ... ... ... ... 453 Table 4.2.2 Percentage frequencies of bacteria pathogen isolation from specimens
taken from inpatients with diagnosis of various infections ... ... ... 466 Table: 4.2.3 Summary table of associations of bacterial pathogens with specimens
and clinical infections ... 497 Table 4.2.4 Percentage sensitivities of gram-positive cocci/bacilli isolates to formulary
antibiotics - January 2000 - June 2006 ... 502 Table 4.2.5 Percentage sensitivities of gram-negative bacilli/cocci isolates to formulary
antibiotics - January 2000 - June 2006 ... 503 Table 4.2.6 Yearly percentage pathogen resistances to ampicillin from Jan 2000 to
Dec 2005 ... 530 Table 4.2.7 Yearly percentage pathogen resistances to penicillin from Jan 2000 to
Dec 2005 ... 530 Table 4.2.8 Yearly percentage pathogen resistances to erythromycin from Jan 2000 to
List of Tables
Table 4.2.9 Yearly percentage pathogen resistances to methicillin cloxacillin from
Jan 2000 to Dec 2005 ... 535 Table 4.2.10 Yearly percentage pathogen resistances to tetracycline from Jan 2000 to
Dec 2005 ... 540 Table 4.2.11 Yearly percentage pathogen resistances to co-trimoxazole from Jan 2000 to
Dec 2005 ... 540 Table 4.2.12
Table 4.2.13
Yearly percentage pathogen resistances to chloramphenicol from Jan 2000 to Dec 2005 ... Yearly percentage pathogen resistances to TGCs (CefotaximeICeftriaxone) from Jan 2000 to Dec 2005 ... ...
546 546 Table 4.2.14 Yearly percentage pathogen resistances to gentamicin from Jan 2000 to
Dec 2005 ... 552 Table 4.2.15 Yearly percentage pathogen resistances to amikacin from Jan 2000 to
Dec 2005 ... 552 Table 4.2.16 Yearly percentage pathogen resistances to ciprofioxacin from Jan 2000 to
Dec 2005 ... 556 Table 4.2.17 Yearly percentage pathogen resistances to nalidixic acid from Jan 2000 to
Dec 2005 ... 556 Table 4.2.18 Yearly percentage pathogen resistances to nitrofurantoin from Jan 2000 to
Dec 2005 ... 556 Table 4.2.19 Antibiotic selection in the empiric treatment of infections based
on antibiotic activity and cost considerations. ... 583 Table 4.3.1 Frequencies of questionnaire distribution within and collection from study
site Health Service Areas (HSAs). ... ... ... ... ... ... ... ... 596 Table 4.3.2
Table 4.3.3
Percentage frequency distributions of respondents by their demographic data .... Frequency distributions of respondents by qualification and according to
Indications of daily patient .... ... ... ... ...
601 602 Table 4.3.4 Frequency distributions of respondents by qualification and according to
patient types ... , ... ... ... ... ... 602 Table 4.3.5 Frequency distribution of respondents by qualification and according to
availability of microbiology laboratory at practice sites ... 603 Table 4.3.6 Frequency distribution of respondents by qualification and according to response
indications of whether or not available microbiology laboratories have capacity
to perform culture sensitivity tests. ... 603 Table 4.3.7 Frequency distribution of respondents with laboratory facilities by qualification
and according to response indications of whether or not available microbiology laboratories provide information on grams stain and morphological
characteristics of pathogens ... '" ... .... 604 Table 4.3.8 Frequency distributions of respondents according to degrees to which patient
biomedical factors affect their decisions to prescribe antibiotics (Question 9(i)) ... 614
Table 4.3.9 Frequency distributions of respondents by qualifications and according to degrees to which they are made to prescribe antibiotics to satisfy patients'
request for them '" ... ... ... ... ... ... ... .... ... ... ... .... . ... ... ... ... ... ... ... 614 Table 4.3.10 Frequency distributions of respondents by qualifications and according to
degrees to which they are made to prescribe to satisfy patients' expectations
regarding treatment they hoped to getfor their ailment... ... ... ... 616 Table 4.3.11 Frequency distributions of respondents by qualifications and according to
degrees to which they are made to prescribe antibiotics by their desire to
eliminate an infection in cases of unclear diagnosis (Question 9iv) ... .... 616 Table 4.3.12 Frequency distribution of respondents by qualifications and according to degrees
to which their decision to prescribe antibiotics is influenced by their desire to
prevent an infection even if bacterial infection is ruled out (Question 9(v)) ... ... 617 Table 4.3.13 Frequency distributions of respondents by qualifications and according to
degrees to which their past experiences influence their decisions to prescribe
antibiotics (Question 9vi). ... 617 Table 4.3.14 Frequency distributions of respondents by qualification and indications of
how often they prescribe antibiotics in outpatient settings on suspicion
of presence of infection (Question 10(i) ... 628 Table 4.3.15 Frequency distributions of respondents by qualification and indications of
how often they prescribe antibiotics in outpatient settings only after
they positively establish presence of infection following patient examination ... 628 Table 4.3.16 Frequency distributions of respondents by qualification and indications
of how often they prescribe antibiotics in outpatient settings only after
laboratory investigations establish the presence of infection ... '" ... ... .... 630 Table 4.3.17 Frequency distributions of respondents by qualification and indications
of how often they prescribe antibiotics in outpatient settings even if they
are not sure of their diagnosis ... ... 630 Table 4.3.18(a) Percentage frequency distributions of respondents in outpatient settings
according to how often they prescribe antibiotics in practice without
establishing presence of infection... ... ... ... ... .... 632 Table 4.3.18(b) Percentage frequency distributions of respondents in outpatient
List of Tables
Table 4.3.19 Frequency distributions of respondents by qualification and indications of whether or not they request for rapid microscopic identification of
pathogens prior to prescribing antibiotics for treatment in inpatient settings... 640 Table 4.3.20 Frequency distributions of respondents by qualification and indications of
whether or not they send specimens for culture sensitivity tests before
initiating empiric antibiotic treatment in inpatient settings ... ... ... ... ... 640 Table 4.3.21 Frequency distributions of respondents by qualification and indications of
whether or not they send specimens for culture sensitivity tests only after
patient non response to initial empiric antibiotic treatment in inpatient settings ... 641 Table 4.3.22 Frequency distributions of respondents by qualification and indications of whether
or not they revise antibiotic treatment by discontinuing initially prescribed antibiotics and replacing them for antibiotics to which organisms show sensitivity. ... ... 641 Table 4.3.23 Frequency distributions of respondents by qualification and indications of
whether or not they revise antibiotic treatment by adding to initially
prescribed antibiotics, antibiotics to which organisms are sensitive ... 642 Table 4.3.24 Frequency distributions of respondents in inpatient settings with laboratory
facilities according to how often they observe or violate principles of antibiotic
prescribing. ... ... ... ... ... .... 644 Table 4.3.25 Frequencies of respondents' scores in test of knowledge in principles of
antibiotic selection and prescribing ... 654 Table 4.3.26 Frequency distribution of respondents by qualifications and according to
performance scores and classifications ... 656 Table 4.3.27 Frequency distribution of respondents by qualification and according
to correctness assessment of stated signs of URTI ... 658 Table 4.3.28 Percentage frequency distribution of respondents according to signs
and symptoms indicated for URTI ... 659 Table 4.3.29 Frequency distribution of respondents by qualification and according to
correctness assessment of stated signs and symptoms of LRTI ... 660 Table 4.3 30 Percentage frequency distribution of respondents according to signs
and sym ptoms indicated for LRTI ... 660 Table 4.3.31 Frequency distribution of respondents by qualification and according to
correctness assessment of stated signs and symptoms of NSTUTI ... 661 Table 4.3.32 Percentage frequency distribution of respondents according to signs
Table 4.3.33 Frequency distribution of respondents by qualification and according to correctness assessment of bacterial pathogens stated as being
associated with URTI ... '" ... '" ... ... ... ... ... ... ... ... ... ... ... 663 Table 4.3.34 Frequency distribution of respondents according to their indications of
bacterial pathogens commonly associated with URTI. ... ... ... 663 Table 4.3.35 Frequency distribution of respondents by qualification and according
to correctness assessment of stated bacterial pathogens associated
with LRTI ... ... ... ... ... ... ... ... ... ... 665 Table 4.3.36 Frequency distribution of respondents according to their indications of
bacterial pathogens commonly associated with LRTI ... 666 Table 4.3.37 Frequency distribution of respondents by qualification and according to
correctness assessment of stated bacterial pathogens associated with
NSTUTI ... 667 Table 4.3.38 Frequency distribution of respondents according to their indications of
bacterial pathogens commonly associated with UTI ... 668 Table 4.3.39 Frequency distribution of respondents according to their indications of
antibiotics of choice in gram-positive cocci infections of surgical wound ... 670 Table 4.3.40 Frequency distribution of respondents according to their indications of
antibiotics of choice in gram-negative bacilli infections of surgical wound ... 670 Table 4.3.41 Frequency distributions of respondents according to degrees to which they
consider in practice factors of cost of antibiotics in the selection of antibiotics ... 673 Table 4.3.42 Frequency distributions of respondents according to degrees to which they
consider in practice factors of bacterial pathogen antibiotic sensitivity in the
selection of antibiotics. ... ... ... ... ... ... .. ... 673 Table 4.3.43 Frequency distributions of respondents according to other factors considered
in the selection of antibiotics. ... 674 Table 4.3.44 Frequency distribution of respondents by qualifications and according
to degrees to which antibiotic stock outs limit choice of antibiotics... ... 700 Table 4.3.45 Frequency distribution of respondents by practice types and according to
degrees to which antibiotic stock outs limit choice of antibiotics... ... 700 Table 4.3.46 Frequency distribution of respondents by qualifications and according to
response indications as to whether or not they ask patients to buy
1st choice prescribed antibiotics ... ... ... ... 702 Table 4.3.47 Frequency distribution of respondents by practice types and according to
response indications as to whether or not they ask patients to buy 1st choice
List of Tables
Table 4.3.48 Frequency distribution of respondents by qualifications and according to response indications as to whether or not they prescribe 2nd choice in place
of 1st choice prescribed antibiotics ... ... ... 703
Table 4.3.49 Frequency distribution of respondents by practice types and according to response indications as to whether or not they prescribe 2nd choice
in place of 1 st choice prescribed antibiotics... 703
.Table 4.3.50 Frequency distributions of respondents with laboratory facilities according to their indications of whether or not they request for rapid microscopic identification or Grams stain characteristics of bacterial pathogens
before antibiotic therapy initiation ... ... ... ... 711 Table 4.3.51 Frequency distributions of respondents indicating they make requests for
microscopic identification of infecting pathogens according to their practice
sites and time lengths of receiving feed back from laboratories. ... 711 Table 4.3.52 Frequency distributions of respondents who do not request for microscopic
identification or Gram stain characteristics of bacterial pathogens prior to prescribing antibiotics according to reasons for not requesting for such
information. ... 712 Table 4.3.53 Frequency distribution of respondents according to their qualifications
and perceptions on need for antibiotic prescription guidelines. ... ... 718 Table 4.3.54 Frequency distribution of respondents according to their qualifications and
LIST OF FIGURES Page Figure 2.1 Comparison of the structure and composition of gram-positive and
gram-negative bacteria cell walls ... ... ... 19 Figure 3.1 Framework of general procedural steps in the conduct of all phases of the
study... ... ... ... ... ... ... ... .... 203 Figure 3.2 Empirical research Phase I: Framework of procedures of data
collection and analysis in antibiotic prescribing pattern study... ... 206 Figure 3.3 Empirical research Phase II: Framework of procedures of data collection and
analysis in determining bacterial isolate sensitivity patterns... ... 233 Figure 3.4 Empirical research Phase III: Framework of Questionnaire
development and administration ... 247 Figure 4.1.1 Percentage frequency distribution of prescriptions according to study sites ... 268 Figure 4.1.2 Percentage frequency distribution of prescription categories according to ward
types ... ... ... ... ... .. ... ... ... 277 Figure 4.1.3 Percentage frequency distributions of numbers of prescribed antibiotics per
prescription used in treating infections among inpatients
311 Figure 4.1.4 Percentage frequencies of number of prescribed antibiotics per prescription
at study sites ... ,... ,... '" .. 312 Figure 4.1.5 Percentage frequency distributions of numbers of prescribed antibiotics per
prescription within prescription categories... ... ... ... 314 Figure 4.1.6 Percentage frequencies of diagnosed infections treated at inpatient settings
at all study sites... ... ... ... ... ... ... ... 330 Figure 4.1.7 Percentage frequencies of prescribed antibiotics in inpatient departments
within study period (June 15 -July 15 2006) ... 333 Figure 4.1.8 Percentage frequency distribution of outpatient patient prescriptions by
study site ... '" ... ... . .. ... ... ... ... .. .. ... ... ... ... .. ... 365 Figure 4.1.9 Frequency distribution of prescriptions according to indicated categories of
appropriateness at respective study sites... ... ... 367 Figure 4.1.10 Frequencies of average costs of prescriptions for categories of prescription
used for treatment... ... . .. ... ... ... ... ... ... ... ... .. . ... ... .. . ... ... ... .. . ... .... ... .... 378 Figure 4.1.11 Percentage frequencies of prescriber diagnosed cases of indicated infection
List of figures
Figure 4.1.12 Percentage frequencies of antibiotic prescribing in outpatient departments at
study sites (June 15 -July 152006) ... '" ... ... ... 412 Figure 4.1.13 Percentage frequencies of isolation of bacterial pathogens form urine specimens
of communal patients presenting with urinary tract infections at study sites
Figure 4.2.1 Frequencies of pathogen isolation at study sites from Jan 2000 to June 2006... 454 Figure 4.2.2 Frequency distribution of bacteria isolates from all study sites from
Figure 4.2.3 Percentage frequency distributions of gram-positive cocci isolates at study
Figure 4.2.4 Percentage frequency distributions of gram-negative bacilli isolates at study
Figure: 4.2.5 Frequencies of Neisseria spp (gram-negative cocci) isolation at study sites
Figure 4.2.7 Percentage incidences of isolation of bacterial pathogens from Cerebrospinal
Figure 4.2.16 Percentage incidences of isolation of bacterial pathogens from Penile
Figure 4.2.17 Percentage incidences of isolation of bacterial pathogens from High
(June 16toJuly31,2006 ... 436
Jan 2000 to June 2006 ... 454
sites (Jan 2000 to June 2006) ... ... ... ... ... ... ... 455
sites (Jan 2000 to June 2006) ... ... ... 455
from Jan 2000 to June 2006. ... ... 457 Figure 4.2.6 Percentage incidences of isolation of bacterial pathogens from Ascitic fluid .... 468
Fluid ... ... ... 468 Figure 4.2.8 Percentage incidences of isolation of bacterial pathogens from Pleural fluid... 469 Figure 4.2.9 Percentage incidences of isolation of bacterial pathogens from Ear swab .. .... 470 Figure 4.2.10 Percentage incidences of isolation of bacterial pathogens from Throat swab ... 472 Figure 4.2.11 Percentage incidences of isolation of bacterial pathogens from Eye swab 472 Figure 4.2.12 Percentage incidences of isolation of bacterial pathogens from Pus swab 473 Figure4.2.13 Percentage incidences of isolation of bacterial pathogens from Blood ... 474 Figure 4.2.14 Percentage incidences of isolation of bacterial pathogens from Sputum.. ... ... ... 475 Figure 4.2.15 Percentage incidences of isolation of bacterial pathogens from Urine.. ... .... 476
discharge .. ... ... ... ... 477
vaginal swab ... ... ... ... ... ... ... ... ... .... 478 Figure 4.2.18(a) Yearly variations in percentage pathogen resistances to ampicillin
Figure 4.2.18(b) Figure 4.2.19( a) Figure 4.2.19(b) Figure 4.2.20(a) Figure 4.2.20(b) Figure 4.2.21 (a) Figure 4.2.21 (b) Figure 4.2.22(a) Figure 4.2.22(b) Figure 4.2.23(a) Figure 4.2.23(b) Figure 4.2.24(a) Figure 4.2.24(b) Figure 4.2.25(a)
Pathogen yearly resistances to ampicillin showing increases or
decreases of pathogens' average resistance rates in 2001-2005 higher than or below their 2000 resistance rates ... 531 Yearly variations in percentage pathogen .resistances to penicillin from
year 2000 to 2005 ... 532 Pathogen yearly resistances to penicillin showing increases or
decreases of pathogens' average resistance rates in 2001-2005 higher than or below their 2000 resistance rates ... '" ... 532 Yearly variations in percentage pathogen resistances to erythromycin
from year 2000 to 2005 ... 536 Pathogen yearly resistances to erythromycin showing increases or
decreases of pathogens' average resistance rates in 2001-2005 higher than or below their 2000 resistance rates ... 536 Yearly variations in percentage pathogen resistances to methicillin!
cloxacillin from year 2000 to 2005 ... ... ... 537 Percentage yearly resistances Staphylococcus aureus of to methicillin!
Cloxacillin showing increases of pathogen's average resistance rate in
2001-2005 higher than its 2000 resistance rates ... , .... '" ... ... 537 Yearly variations in percentage pathogen resistances to tetracycline
from year 2000 to 2005 ... ... ... ... ... ... ... ... ... .... 541 Pathogen yearly resistances to Tetracycline showing increases
or decreases of pathogens' average resistance rates in 2001-2005
higher than or below their 2000 resistance rates ... ... 541 Yearly variations in percentage pathogen resistances to co-trimoxazole from year 2000 to 2005 ... 542 Pathogen yearly resistances to co-trimoxazole showing increases or
decreases of pathogens' average resistance rates in 2001-2005 higher than or below their 2000 resistance rates... ... ... ... ... 542 Yearly variations in percentage pathogen resistances to chloramphenicol from year 2000 to 2005 ... 547 Pathogen yearly resistances to chloramphenicol showing increases
or decreases of pathogens' average resistance rates in 2001-2005 higher than or below their 2000 resistance rates ... .... ... 547 Yearly variations in percentage pathogen resistances to TGC from year 2000 to 2005 ... 548
List of figures Figure 4.2.25(b) Figure 4.2.26(a) Figure 4.2.26(b) Figure 4.2.27(a) Figure 4.2.27(b) Figure 4.2.28(a) Figure 4.2.28(b) Figure 4.2.29(a) Figure 4.2.29(b) Figure 4.2.30(a) Figure 4.2.30(b) Figure 4.3.1 Figure 4.3.2 Figure 4.3.3
Pathogen yearly resistances to TGC (cefotaxime/ceftriaxone) showing increases or decreases of pathogens' average resistance rates in
2001-2005 higher than or below their 2000 resistance rates. ... 548 Yearly variations in percentage pathogen resistances to gentamicin from year 2000 to 2005 ... 553 Pathogen yearly resistances to gentamicin showing increases or
Decreases of pathogens' average resistance rates in 2001-2005 higher than or below their 2000 resistance rates... ... 553 Yearly variations in percentage pathogen resistances to amikacin
from year 2000 to 2005 ... 554 Pathogen yearly resistances to amikacin showing increases or decreases of pathogens' average resistance rates in 2001-2005 higher than or below their 2000 resistance rates ... 554 Yearly variations in percentage pathogen resistances to ciprofloxacin
from year 2000 to 2005 ... 557
Pathogen yearly resistances to ciprofloxacin showing increases or decreases of pathogens' average resistance rates in 2001-2005 higher
than or below their 2000 resistance rates ... 557 Yearly variations in percentage pathogen resistances to nalidixic acid
from year 2000 to 2005 ... 558 Pathogen yearly resistances to nalidixic acid showing increases
or decreases of pathogens' average resistance rates in 2001-2005
higher than or below their 2000 resistance rates ... 558 Yearly variations in percentage pathogen resistances to nitrofurantoin
from year 2000 to 2005 ... 561 Pathogen yearly resistances to nitrofurantoin showing increases or
decreases of pathogens' average resistance rates in 2001-2005 higher than or below their 2000 resistance rates ... 561
Percentage distribution of respondents according to qualification ... 597 Respondents' scores in test of knowledge in principles of
antibiotic selection and prescribing ... 654 Percentage frequency distribution of respondents by their qualifications and according to their descriptive performance levels in knowledge test. .. 655
Appendix 2 Data collection tool -2: Individual outpatient data collection sheet. ... ... ... 806 Appendix 3 Data collection tool: 3 Antibiotic prescription data summary tool for prescription
rationality rating - Inpatients ... ... 807 Appendix 4 Data collection tool: 4 Antibiotic prescription data summary tool for prescription
rationality rating - Outpatients... ... 808 Appendix 5 Examples of antibiotic prescriptions classified into categories of appropriateness
according to employed method of assessment... ... ... ... 809 Appendix 6 Guidelines for interpreting case note indicated diagnosis/symptom complexes
in the establishment of the presence or absence of bacterial infections. ... ... 814 Appendix 7 Characteristics of antibiotics routinely used in Lesotho ... 841 Appendix 8 Data collection tool: 5 Antibiotic prescription data summary tool for inpatient
treatment cost determination. ... ... ... ... 845 Appendix 9 Data collection tool no. 6: Antibiotic prescription data summary tool for
outpatient treatment cost determination ... 846 Appendix 10 Data collection tool no. 7: Antibiotic cost data collection tool 847
Appendix 11 Data collection tool no. 8: Pathogen antibiotic culture sensitivity test
results data collection form. ... 848 Appendix 12 Calculated percentage overall activities (POA) of antibiotics against major
pathogens associated with infections among inpatients and outpatients. ... ... ... 849
Appendix 12 (i) Percentage over all activity determinations of antibiotics against major pathogens associated with ascites among inpatients (Source of isolates:
Ascitic fluid from inpatients) ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... 849 Appendix 12 (ii) Percentage overall activity determinations of antibiotics against major
pathogens associated with CNS infections (meningitis) among inpatients (Source of isolates: Cerebrospinal fluid from inpatients) ... 850 Appendix 12 (iii): Percentage overall activity determinations of antibiotics against major
pathogens associated with lower respiratory tract infections among
