ANTIBIOTICS CONSUMPTION AMONG HOSPITALIZED PATIENTS IN INTENSIVE CARE UNITS AT SANA’A CITY, YEMEN

Ghamdan A. Al-Tahish1image, Ali A. Alyahawi*2image

1Faculty of Laboratory Medicine, 21 September University, Republic of Yemen.

2Faculty of Clinical Pharmacy, 21 September University, Republic of Yemen.

 

Abstract

Background: Monitoring antibiotic consumption is crucial to addressing antimicrobial resistance. The aim of current study was to investigate the use and consumption of antibiotics in an intensive care unit in Sana'a, Yemen using DDD and DOT methods, and to our knowledge it is the first of its kind to study this topic.

Methods: A retrospective study on data from the ICU register. The study was carried out from September 2021 to February 2022 on hospitalized  patients of five ICUs of main hospitals at 2020. Antimicrobial consumption data were mostly collected manually. Data were analyzed and presented as defined daily dose (DDD) and days of therapy (DOT) per 1000 patient-days.

Results: A total of 1970 patients were included in this study and the overall consumption of antibiotics in ICUs was as high as 18,017.91 DDD per 1000 patient-days and as high as 17448.73 DOT per 1000 patient-days. The study results found that ceftriaxone, vancomycin, and meropenem were most frequently consumed using DDD and DOT methods among ICU patients, with results by DDDs per 1000 patient-days being 2479.23, 2124.55, and 1830.54, respectively, and results by DOTs per 1,000 patient days being 2,112.69. 2055.33 and 1890.86. The highest amount of antibiotics consumption among WHO AWaRe classification was for "watch" group of 26267.4 and 14674.5 DDDs per 1000 patient per day.

Conclusions: A high consumption of antimicrobial agents such as ceftriaxone, vancomycin and meropenem was found in ICUs of five selected hospitals. There was a significant increasing in “Watch” group antibiotics use and about three-fourths of the prescribed antibiotics were from this group. The study results can be used as a basis before designing any intervention aimed at improving antibiotic use in hospital intensive care units.

Keywords: Antibiotic consumption, AWaRe classification, DDD, DOT, ICUs.

 

INTRODUCTION

 

Antibiotics are currently encountering significant global public health challenges, such as antimicrobial resistance and inappropriate use1. According to the World Health Organization (WHO), more than two-thirds of antibiotics are administered in hospitals, and approximately 30% of these are used inappropriately on a global scale2. A strong correlation exists between high antibiotic consumption and resistance, which is exacerbated by irrational antibiotic use at both individual and community levels3.

The misuse and resistance of antibiotics have emerged as critical public health issues, with alarming evidence accumulating over recent years regarding their inappropriate utilization4,5. In low- and middle-income countries (LMICs), about one-third of antibiotic use is inappropriate, with nearly 90% of prescribed antibiotics being broad-spectrum agents, such as third or fourth-generation cephalosporins, highlighting the need for Antimicrobial Stewardship Programs in hospitals6.

To monitor the consumption of antimicrobials and promote the prudent use of antibiotics, the WHO developed a methodology for antimicrobial consumption surveillance using a metric, the defined daily dose (DDD), as per the anatomical, therapeutic and chemical classification (ATC) system. The WHO has classified antibiotics into three categories as AWaRe: Access for antibiotics needed for common infections that should be available and accessible, Watch for broad-spectrum antibiotics that should be used with caution because of their high potential to develop resistance and reserve for antibiotics that should be reserved for the treatment of multidrug-resistant infections and used only when other alternatives fail7.

 The intensive care unit (ICU) is often called the epicenter of infections, due to its extremely vulnerable patients, the wide use of invasive devices and broad-spectrum antimicrobials, which favors the emergence of multidrug resistance (MDR). The prognosis of patients who develop hospital-acquired infections (HAI) in the ICU is poor and the mortality rates are higher if it involves an MDR organisms. Inappropriate use of broad- spectrum antimicrobials is frequent, partly because of unwarranted prescriptions of antimicrobials, which may be caused by uncertainty regarding the type of infection, among other possible explanation8-11.

Yemen is among the developing nations where antimicrobial resistance (AMR) promote inappropriate and overuse of antimicrobial consumption are posing a danger to public health12-24. The magnitude of antimicrobial consumption in Yemen unknown, because no previous published studies and reports that addressed this subject using WHO metrics, so this study aimed to estimate antibiotic consumption in ICUs of hospitals by using DDD and DOT methods in Sana'a, Yemen. The study results can be used as base before designing any intervention aiming to optimize antibiotics utilization in hospitals ICUs.

 

MATERIALS AND METHODS

 

Study design

Aretrospectivestudy of medical records for all admissions to the ICUs. The study was carried out from September 2021 to February 2022on hospitalized   patients in ICUs of main hospitals at 2020.

Study area:

This study was conducted in five main hospitals at Sana'a city–Yemen, three of them were public hospitals and two were private. Public hospitals included Al-Thawra Modern General Hospital (ATH) AL- Jomhori Teaching Hospital (AJH) and 48 Hospital (48H), while private hospitals included Dr. Abdulkader Almutawakel Hospital (AMH) and University Science and Technology Hospital (USTH).

Study population

All patients admitted in ICUs of these hospitals at 2020. All the data was collected manually from patient records except data of USTH was electronic.

Sample size

 All adult patients admitted to ICUs with prescribed and received antibiotics of five hospitals during 2020 were included (1970 patients) in this study.

Excluded data

All children admitted  to ICUs was excluded because the WHO developed the DDD as a unit of drug use, which is defined as the average daily dose of a drug for its main indication in adults.. Patients who lacked data on prescribed and received medications also were excluded.

Data collection

Data of patients in ICUs were extracted from the ICU patient register by fourth-year Laboratory Medicine students that well trained according to an organized questionnaire containing several variables included the age of a patient, sex, entry day, discharge day, inpatient days or admission, inpatient days or admission name of antimicrobial with strength, strength antibiotic type (tab, vial, amp, syr, sus), antibiotic description (dose No/day/period), route of administration (oral, IM,IV) antibiotic scientific name, antibiotic class, antibiotic subclass.                

Defined Daily Dose Method (DDD)

To estimated antimicrobial use using the DDD method, the total number of grams of each antimicrobial used during the period of study were summed and divided by the WHO-assigned DDD. Dividing total grams of use by the DDD (grams/day) yields an estimate of the number of days of antimicrobial therapy. All DDDs were based on the 2020 version of the ATC classification system. To express aggregate use, total DDDs were normalized per 1000 patient-days.

Days of Therapy Method (DOT)

To estimate antibiotic use using the DOT method, one DOT represented the administration of a single agent on a given day, regardless of the number of doses administered or dosage strength. A single patient receiving two antimicrobial drugs would be recorded as receiving 2 DOTs (1 for each antimicrobial administered) and so on according to the number of antimicrobials received daily. To express aggregate use, total DOTs were normalized to 1000 patient-days.

World Health Organization Essential Medicine List (WHO 2019) “Access, Watch, and Reserve (AWaRe)” antibiotics classification were used to assess antibiotic use pattern among participants.

Statistical analysis

All data were coded and entered into a Microsoft Excel file. The spreadsheet was used for the calculation of DDDs based on the strength of each antibiotic, the number of dose units and the DDD values allocated by the World Health Organization. The statistical analyses were done using SPSS version 22.0 software package for windows. Measures of relative consumption, expressed as a percentage of total consumption of groups of antibiotics, were derived for each antibiotic and DDD for “Watch” and “Access” category of antibiotics was calculated.

Ethical Approval

Ethical clearance was obtained from the qualified authorities. The study protocol was approved by the ethics committee of hospitals and 21 September University.

 

RESULTS

 

A total of 1970 patients were included in this study. The data of admitted patients of ICUs hospitals at 2020 was collected from patient recorders of five selected hospitals at Sana’a city. This study was conducted from September 2021 to February 2022 and the following results were found:

Demographic characteristics of study participants

A total of 1970 patients their data were collected,1197 from University Science and Technology Hospital (USTH), while only 167, 345, 156 and 105 were collected from 48 Hospital (48H), AL-Thawra Modern General Hospital (ATH), Al-Jomhori Teaching Hospital (AJH), and Dr. Abdulkader Almutawakel Hospital (AMH), respectively. 

The most participated patients showed that 60.7% in this study were from USTH while lowest participation from AMH was 5.3%. Among ICUs patients the males were the majority (67.4 %), more than females (33%) in this study.  The age categories were distributed from 15 years to more than 60 years, and the highest number of participants belong to the oldest age category was (38.5%) while the lowest number belong to the youngest category was (17.2%), as showed in Table 1.

Antimicrobial prescription

As shown in Table 2, on average the number of consumed antimicrobial/patient, amount (in gram) of consumed antimicrobial/patient, number of admission days/patient and days of treatment/patient were 2.67, 8.67, 7.04, 17.45 among ICUs hospitals, respectively. Regarding route of antimicrobial administration, the parenteral route was the most common route in ICUs.

Antimicrobial use patterns by using antibiotics metrics

Table 3 shows the most average of antimicrobial consumption regarding antimicrobial consumption using DDDs and DOT in ICUs patients were ceftriaxone, vancomycin, and meropenem reported 2479.23, 2124.55 and 1830.54 DDDs per 1000 patient-days, respectively. While the average amount of polymyxin B, tigecycline, and colistin were 670.05, 294.42, and 8.68 DDDs per 1000 patient-days, respectively. On the other side, the most average of antimicrobial consumption using DOTs, reported ceftriaxone, vancomycin, and meropenem with 2112.69, 2055.33, and, 1890.86 DOTs per 1000 patient-days, respectively. The same antibiotics were reported by both methods. The Table 4 shows a total consumption of antibiotic for systemic use was 18017 DDD per 1000 patient-days.

The vast majority of consumption among therapeutic/Pharmacological subgroups consisted of cephalosporins (3882 DDD per 1000 patient-days), while carbapenems (2987 DDD per 1000 patient-days) and quinolones (2900 DDD per 1000 patient per days). The rate of DOTs per 1000 patient-days were cephalosporins was 4227.41DOTs per 1000 patient-days, while carbapenems was 2888.83DOTs per 1000 patient-days, and quinolones was 2660.41DOTs per 1000 patient-days.

DISCUSSION

 

Excessive exposure to antibiotics fosters a complicated relationship between antibiotic resistance and the irrational use of these medications25. Understanding the extent of antibiotic exposure and patterns of antibiotic use is crucial for preventing inappropriate usage and its consequences26. The findings of this study highlight a significant concern regarding ICU-specific antimicrobial consumption in five hospitals in Sana’a, Yemen.

The high consumption rates, as indicated by both DDD and DOT methods, mirror patterns observed in other regions grappling with antimicrobial resistance challenges. In the present  study the  total consumption  by DDD/1000 patient- days  of antimicrobials was 18017 that higher than reported from studies in Brazil, Saudi Arabia, Romania and from 130 European hospitals that reported  14368.85  and  812.5,  1172.40,  792±147, respectively7,8,27,28.

In current study, ceftriaxone, vancomycin, and meropenem were the most frequently consumed antibiotics in ICUs irrespective of the metrics used. this finding align with study conducted in Saudi Arabia which also reported the  highest usage of ceftriaxone and vancomycin29. Similarly, studies  carried out in Brazil and America Latin observed that meropenem and vancomycin were the most highly consumed antibiotics27,30. The frequent prescription of broad spectrum antibiotic like ceftriaxone in intensive care units has been consistently reported in various studies27,31-34. These observations are in the line with our findings, indicating a common trend in the high utilization of these antibiotics in critical care setting. On the other hand, the majority of international studies have showed that penicillins35-37 are the most frequently consumed antimicrobials in adult ICUs.

The high usage of cephalosporins, carbapenemsand quinolones aligns with global consumption patterns, particularly in low and middle-income countries where empirical therapy is common due to limited diagnostic facilities38. The elevated consumption of these broad-spectrum antibiotics raises concerns about the potential acceleration of antimicrobial resistance. In line with our findings, the majority of international studies have showed that cephalosporins39-41 are the most frequently consumed antimicrobials in adult ICUs.

Cephalosporins consumption  was 3882.95 by DDD / 1000 patient-days higher  than 2135.08 and  264.19 that reported from  other studies8, 27. The consumption of carbapenems in this study was considerably higher than the rates reported by several reports around the world. For example, it was 2987  DDDs per 1000 patient-days in current ICUs compared with 255.9  in Saudia7,36.9 in French ICUs35, 37.8 in the US National Nosocomial Infections Surveillance (NNIS) medical-surgical ICUs36, 81.4 in German ICUs37, 90.0 in the International Nosocomial Infection Control Consortium (INICC) ICUs39, 58–143 in Swedish ICUs40, 196.5 in Italian ICUs41, and 257.1 in Australian and New Zealand ICUs42.

The consumption of vancomycin in this study was 1830.54 DDDs per 1000 patient-days which was higher than Saudi ICUs 98.27, NNIS, INICC, and German ICUs (36.7–91.9)36,37,39, also in Italian and Australian and New Zealand ICUs (146.9–191.8)42,43. In contrary, study carried out by T.L. de Castro et al., in 2023 reported higher rate of carbapenems and vancomycin consumption than our results; 3110,02 and 2322.6  DDDs per 1000 patient-days27.

Comparing the current ICU-specific DOT rates, this study had  DOTs per 1000 patient-days  of 2888.83 for  carbapenems consumption  that significant higher than 235.7 and 196.3 reported by studies done in an adult ICU in  Saudi Arabia7  and Canada41. Vancomycin reported  2055.33  by DOTs per 1000 patient-days, that higher than reported  in the previous studies; 129.5 and  187.27,41.

The most frequently consumed antibiotics according to therapeutic/pharmacological subgroup were cephalosporin's, carbapenem and quinolones consisting mainly of parenteral. The current study showed that 73% of antibiotics used were from the “Watch” group antibiotics. This finding is slightly higher  than  the survey that reported  in Ethiopia; 66%27, 66.1% in West and Central Asia44, and 64.4% in four low and middle-income countries45. This "watch"  includes antibiotics that are at a higher risk of resistance and should be prioritized for stewardship efforts46. The high consumption rates of these antibiotics in our study reiterate the necessity for stringent guidelines to monitor and control their use.

The high consumption of broad spectrum antimicrobials was due to the prevalence of infections caused by gram-negative bacteria that produce extended-spectrum β-lactamase (ESBL) and methicillin-resistant Staphylococcus aureus (MRSA), respectively30. One of the reasons for the significant differences in antibiotic consumption in our study compared to similar studies in other countries can be attributed to the ongoing military conflict in Yemen. This conflict has led to a significant influx of injured soldiers and civilians into the capital's hospitals. In addition, the COVID-19 outbreak that occurred during the study period had a major impact on the healthcare system in Yemen. Many COVID-19 patients, including those with severe and critical illness, were admitted to the study hospitals. Furthermore, there is a lack of a clear, standardized treatment policy for critical cases. So, all these factors may contribute to the substantial difference in antibiotic consumption in the study hospitals. Additionally, the high prevalence of antibiotic-resistant bacteria in these hospitals has led to the excessive use of broad-spectrum antibiotics47-49. 

Limitations of the study

A major limitation of this study was the inability to access all data of patients admitted to most hospitals due to administrative constraints and the unavailability of an electronic patient data system which facilitates data acquisition rather than manually collecting them from the ICU registry. Finally, the study was not designed to take into account working differences between ICUs in patient mix or predominant bacterial pathogens and their susceptibility patterns.

CONCLUSIONS

 

Current results show a high consumption of broad-spectrum antimicrobial agents such as cephalosporin and carbapenem in addition to vancomycin by patients of   intensive care units of 48H, ATH, AJH, AMH and USTH. The consumption of ceftriaxone, vancomycin, and meropenem were the highest using both DDD and DOT methods among ICU patients. The findings highlight the urgent need for an effective antimicrobial stewardship program in these hospitals with focusing on ICUs specific antimicrobial consumption. The study results can be used as base before designing any intervention aiming to optimize antibiotics utilization in hospitals ICUs. 

 

ACKNOWLEDGEMENTS

 

The authors extend their thanks and appreciation to the University Science and Technology Hospital, Al-Thawra Modern General Hospital, AL- Jomhori Teaching Hospital, 48 Hospital and Dr. Abdulkader Almutawakel Hospital, Republic of Yemen to provide necessary facilities for this work. 

 

AUTHOR’S CONTRIBUTION

 

Al-Tahish GA: writing original draft, methodology, investigation. Alyahawi AA: formal analysis, data curation, conceptualization. Final manuscript was read and approved by all authors.

 

DATA AVILIABILITY

 

The data will be available to anyone upon request from the corresponding author.

 

CONFLICT OF INTEREST 

 

None to declare. 

 

REFERENCES

 

  1. Pires D, de Kraker MEA, Tartari E, Abbas M, Pittet D. Fight antibiotic resistance—It’s in your hands’: call from the World Health Organization for 5th may 2017. Clin Infect Dis 2017;64(12):1780-3.https://doi.org/10.1093/cid/cix226
  1. Organization WH. Antimicrobial stewardship programmes in health-care facilities in low-and middle-income countries: a WHO practical toolkit: World Health Organization; 2019.
  2. Bell BG, Schellevis F, Stobberingh E, Goossens H, Pringle M. A systematic review and meta-analysis of the effects of antibiotic consumption on antibiotic resistance. BMC infectious diseases 2014;14:1-25.https://doi.org/10.1186/1471-2334-14-13
  1. Tillotson GS, Zinner SH. Burden of antimicrobial resistance in an era of decreasing susceptibility. Expert Review Anti Infect Ther 2017;15(7):663-76.https://doi.org/10.1080/14787210.2017.1337508
  1. Sulis G, Adam P, Nafade V, et al. Antibiotic prescription practices in primary care in low-and middle-income countries: A systematic review and meta-analysis. PLoS Med 2020;17(6):e1003139.https://doi.org/10.1371/journal.pmed.1003139
  1. Ayukekbong JA, Ntemgwa M, Atabe AN. The threat of antimicrobial resistance in developing countries: Causes and control strategies. Antimicrobial Resis Infec Control 2017;6:1-8. https://doi.org/10.1186/s13756-017-0208-x
  2. Balkhy HH, El-Saed A, El-Metwally A, et al. Antimicrobial consumption in five adult intensive care units: A 33-month surveillance study. Antimicrobial Resis Infec Control 2018;7:1-9.https://doi.org/10.1186/s13756-018-0451-9
  1. Axente C, Licker M, Moldovan R, et al. Antimicrobial consumption, costs and resistance patterns: A two year prospective study in a Romanian intensive care unit. BMC infectious diseases 2017;17:1-9.https://doi.org/10.1186/s12879-017-2440-7
  1. Brusselaers N, Vogelaers D, Blot S. The rising problem of antimicrobial resistance in the intensive care unit. Annals Intens Care 2011;1:1-7.https://doi.org/10.1186/2110-5820-1-47
  1. Xu J, Duan X, Wu H, Zhou Q. Surveillance and correlation of antimicrobial usage and resistance of Pseudomonas aeruginosa: A hospital population-based study. PLoS One 2013;8(11):e78604.https://doi.org/10.1371/journal.pone.0078604
  1. McLaughlin M, Advincula MR, Malczynski M, et al. Correlations of antibiotic use and carbapenem resistance in Enterobacteriaceae. Antimicrobial Agents Chemother 2013;57(10):5131-3.https://doi.org/10.1128/AAC.00607-13
  1. Alyahawi A, Alrubaiee G, Alkaf A. Evaluation of carbapenem use among patients at Intensive Care Unit (ICU) in Sana'a, Yemen. Universal J Pharm Res 2019.https://doi.org/10.22270/ujpr.v4i6.333
  1. Al-Shehari MM, Al-Khamesy KSA, Al-Shamahy HA, et al. Distribution and antibacterial resistance of wound pathogenic bacteria in patients of Sana’a hospitals, Yemen. Universal J Pharm Res 2023.https://doi.org/10.22270/ujpr.v8i3.942
  1. Orubu ES, Al-Dheeb N, Ching C, et al. Assessing antimicrobial resistance, utilization, and stewardship in Yemen: an exploratory mixed-methods study. The American J Trop Med Hyg 2021; 105(5):1404.https://doi.org/10.4269/ajtmh.21-0101
  1. Al-Shami HZ, Al-Haimi MA, Al-Shamahy HA, et al. Patterns of antimicrobial resistance among major bacterial pathogens isolated from clinical samples in two tertiary’s hospitals, in Sana'a, Yemen. Universal J Pharm Res 2021.https://doi.org/10.22270/ujpr.v6i5.674
  1. Alyahawi A, Alkaf A, Alnamer R, Alnosary T. Study of resistance for recently marketed carbapenem drug among hospitalised patients in Sana'a, Yemen. Universal J Pharm Res 2018. https://doi.org/10.22270/ujpr.v3i5.203
  2. Saleh AAM, Al-Shamahy HA, Al-Hrazi RMA, et al. Biofilm formation and antibiotic susceptibility of uropathogens in patients with catheter associated urinary tract infections in ibb City-Yemen. Universal J Pharm Res 2019. https://doi.org/10.22270/ujpr.v4i6.329
  3. Al-Hammadi MA, Al-Shamahy HA, Ali AQ. The prevalence and phenotypic characterization of extended-spectrum β-lactamases-producing Escherichia coli strains isolates recovered from Tertiary Hospitals in Sana'a city, Yemen. Universal J Pharm Res 2018.https://doi.org/10.22270/ujpr.v3i6.220
  1. Al-Safani AMA, Al-Shamahy HA, Al-Moyed KA. Prevalence, antimicrobial susceptibility pattern and risk factors of MRSA isolated from clinical specimens among military patients at 48 medical compound in Sana'a city-Yemen. Universal J Pharm Res 2018:40-4.https://doi.org/10.22270/ujpr.v3i3.165
  1. Al-Haifi AY, Al Makdad ASM, Salah MK, Al-Shamahy HA, Al Shehari WAA. Epidemiology, bacterial profile, and antibiotic sensitivity of lower respiratory tract infections in Sana’a and Dhamar city, Yemen. Universal J Pharm Res 2020. https://doi.org/10.22270/ujpr.v5i2.386
  2. ALhlale MF, Humaid A, Saleh AH, Alsweedi KS, Edrees WH. Effect of most common antibiotics against bacteria isolated from surgical wounds in Aden Governorate hospitals, Yemen. Universal J Pharm Res 2020.https://doi.org/10.22270/ujpr.v5i1.358
  1. Alyahawi A, Alkaf A, Alhomidi AM. Prevalence of Methicillin Resistant Staphylococcus aureus (MRSA) and antimicrobial susceptibility patterns at a private hospital in Sana'a, Yemen. Universal J Pharm Res 2018:4-9.https://doi.org/10.22270/ujpr.v3i3.159
  1. Al-Tahish GAA, Al-Yosaffi EA, Al-Shamahy HA, et al. Prevalence of blatem, blashv, and blactx-m genes among esbl-producing Escherichia coli isolated from the blood samples of icus patients of university hospitals in Sana'a city, Yemen. Universal J Pharm Res 2023.https://doi.org/10.22270/ujpr.v8i6.1032
  1. Alyahawi A, Alhomidi AM, Al-Henhena N. Prevalence of Pseudomonas aeruginosa and antimicrobial susceptibility patterns at a private hospital in Sana'a, Yemen. Universal J Pharm Res 2018. https://doi.org/10.22270/ujpr.v3i4.177
  2. Cantón R, Horcajada JP, Oliver A, Garbajosa PR, Vila J. Inappropriate use of antibiotics in hospitals: The complex relationship between antibiotic use and antimicrobial resistance. Infect Dis Clin Microbiol 2013;31:3-11.https://doi.org/10.1016/S0213-005X(13)70126-5
  1. Dechasa M, Chelkeba L, Jorise A, Sefera B, Melaku T. Antibiotics use evaluation among hospitalized adult patients at Jimma Medical Center, southwestern Ethiopia: The way to pave for antimicrobial stewardship. J Pharm Policy Pract 2022;15(1):84.https://doi.org/10.1186/s40545-022-00490-4
  1. de Castro TL, Cambiais AMVB, Sforsin ACP, Pinto VB, Falcão MAP. Characterization of consumption and costs of antimicrobials in intensive care units in a Brazilian tertiary hospital. Explor Res Clin Soc Pharm 2023;11:100289.https://doi.org/10.1016/j.rcsop.2023.100289
  1. MacKenzie F. Antibiotic consumption in European hospitals. Medicine Infect Dis 2005;35:S121-2.
  2. Alawi MM, Darwesh BM. A stepwise introduction of a successful antimicrobial stewardship program: Experience from a tertiary care university hospital in Western, Saudi Arabia. Saudi Med J 2016;37(12):1350.https://doi.org/10.15537/smj.2016.12.15739
  1. Versporten A, Zarb P, Caniaux I, et al. Antimicrobial consumption and resistance in adult hospital inpatients in 53 countries: results of an internet-based global point prevalence survey. The Lancet Global Health 2018;6(6):e619-e29.https://doi.org/10.1016/S2214-109X(18)30186-4
  1. Ismail D. Cost of antibiotics in medical intensive care. J Hosp Infect 2022;124:47-55.https://doi.org/10.1016/j.jhin.2022.03.003
  1. Wang Y-Y, Du P, Huang F, Li D-J, Gu J, Shen F-M, et al. Antimicrobial prescribing patterns in a large tertiary hospital in Shanghai, China. Int J Antimic Agent 2016;48(6):666-73.https://doi.org/10.1016/j.ijantimicag.2016.09.008
  1. Kayambankadzanja RK, Lihaka M, Barratt-Due A, et al. The use of antibiotics in the intensive care unit of a tertiary hospital in Malawi. BMC Infect Dis 2020;20:1-7.https://doi.org/10.1186/s12879-020-05505-6
  1. Baral P, Hann K, Pokhrel B, et al. Annual consumption of parenteral antibiotics in a tertiary hospital of Nepal, 2017–2019: A cross-sectional study. Public Health Action 2021; 11(1):52-7. https://doi.org/10.5588/pha.21.0043
  2. Dumartin C, L'Hériteau F, Péfau M, Bertrand X, et al. Antibiotic use in 530 French hospitals: Results from a surveillance network at hospital and ward levels in 2007. J Antimicr Chemother 2010;65(9):2028-36.https://doi.org/10.1093/jac/dkq228
  1. Rosenthal VD, Maki DG, Jamulitrat S, et al. International nosocomial infection control consortium (INICC) report, data summary for 2003-2008, issued June 2009. American J Infec Control 2010;38(2):95-104. e2.https://doi.org/10.1016/j.ajic.2009.12.004
  1. Meyer E, Schwab F, Gastmeier P, Rueden H, Daschner F. Surveillance of antimicrobial use and antimicrobial resistance in German intensive care units (SARI): A summary of the data from 2001 through 2004. Infection 2006;34:303-9. https://doi.org/10.1007/s15010-006-6619-x
  2. Hamers RL, van Doorn HR. Antibiotic consumption in low-income and middle-income countries. The Lancet Global Health 2018;6(7):e732.https://doi.org/10.1016/S2214-109X(18)30270-5
  1. Rosenthal VD, Maki DG, Mehta A, et al. International nosocomial infection control consortium report, data summary for 2002-2007, issued January 2008. American J Infect Control 2008; 36(9):627-37.https://doi.org/10.1016/j.ajic.2008.03.003
  1. Walther SM, Erlandsson M, Burman L, et al. Antibiotic prescription practices, consumption and bacterial resistance in a cross section of Swedish intensive care units. Acta Anaesthesiologica Scandinavica 2002;46(9): 1075-81.https://doi.org/10.1034/j.1399-6576.2002.460904.x
  1. Candeloro CL, Kelly LM, Bohdanowicz E, Martin CM, Bombassaro AM. Antimicrobial use in a critical care unit: A prospective observational study. Int J Pharmacy Pract 2012;20(3):164-71.https://doi.org/10.1111/j.2042-7174.2011.00176.x
  1. Vaccheri A, Silvani MC, Bersaglia L, et al. A 3 year survey on the use of antibacterial agents in five Italian hospitals. J Antimicro Chemother 2008;61(4):953-8.https://doi.org/10.1093/jac/dkn010
  1. Dulhunty J, Paterson D, Webb S, Lipman J. Antimicrobial utilisation in 37 Australian and New Zealand intensive care units. Anaesthesia Intensive Care 2011;39(2):231-7.https://doi.org/10.1177/0310057X1103900212
  1. Pauwels I, Versporten A, Drapier N, Vlieghe E, Goossens H. Hospital antibiotic prescribing patterns in adult patients according to the WHO Access, Watch and Reserve classification (AWaRe): Results from a worldwide point prevalence survey in 69 countries. J Antimicrobial Chemother 2021;76(6):1614-24.https://doi.org/10.1093/jac/dkab050
  1. Ingelbeen B, Koirala KD, Verdonck K, et al. Antibiotic use prior to seeking medical care in patients with persistent fever: a cross-sectional study in four low-and middle-income countries. Clin Microbiol Infe 2021; 27(9):1293-300. https://doi.org/10.1016/j.cmi.2020.11.003
  2. Barlam TF, Cosgrove SE, Abbo LM, et al. Implementing an antibiotic stewardship program: Guidelines by the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America. Clin Infect Dis 2016;62(10):e51-e77.https://doi.org/10.1093/cid/ciw118
  1. Al-Mehdar AA, Al-Akydy AG. Pattern of antimicrobial prescribing among in-patients of a teaching hospital in Yemen: A prospective study. Universal J Pharm Res 2017.https://doi.org/10.22270/ujpr.v2i5.R3
  1. Badulla WF, Alshakka M, Mohamed Ibrahim MI. Antimicrobial resistance profiles for different isolates in Aden, Yemen: A cross‐sectional study in a resource‐poor setting. BioMed Research Int 2020;2020(1):1810290.https://doi.org/10.1155/2020/1810290
  1. Grau S, Hernandez S, Echeverria-Esnal D, et al. Antimicrobial consumption among 66 acute care hospitals in Catalonia: Impact of the COVID-19 pandemic. Antibiotics 2021; 10(8):943.https://doi.org/10.3390/antibiotics10080943