Next Article in Journal
The Use of the TARGET Antibiotic Checklist to Support Antimicrobial Stewardship in England’s Community Pharmacies
Next Article in Special Issue
Antibiotic Utilization Patterns for Different Wound Types among Surgical Patients: Findings and Implications
Previous Article in Journal
Phenolic Compounds in Bacterial Inactivation: A Perspective from Brazil
Previous Article in Special Issue
Knowledge, Attitude and Practices of Self-Medication Including Antibiotics among Health Care Professionals during the COVID-19 Pandemic in Pakistan: Findings and Implications
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Antibiotics
Volume 12
Issue 4
10.3390/antibiotics12040646
antibiotics-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles thumb_up
...
Endorse textsms
...
Comment
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

Antibiotic Overprescribing among Neonates and Children Hospitalized with COVID-19 in Pakistan and the Implications

by
Zia UI Mustafa
1,2,
Amer Hayat Khan
1,*,
Sabariah Noor Harun
1,
Muhammad Salman
3 and
Brian Godman
4,5,6,*
1
Discipline of Clinical Pharmacy, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Gelugor 11800, Penang, Malaysia
2
Department of Pharmacy Services, District Headquarter (DHQ) Hospital, Pakpattan 57400, Pakistan
3
Institute of Pharmacy, Faculty of Pharmaceutical and Allied Health Sciences, Lahore College for Women University, Lahore 54000, Pakistan
4
Strathclyde Institute of Pharmacy and Biomedical Science (SIPBS), University of Strathclyde, Glasgow G4 0RE, UK
5
Department of Public Health Pharmacy and Management, School of Pharmacy, Sefako Makgatho Health Sciences University, Pretoria 0208, South Africa
6
Centre of Medical and Bio-Allied Health Sciences Research, Ajman University, Ajman P.O. Box 346, United Arab Emirates
*
Authors to whom correspondence should be addressed.
Antibiotics 2023, 12(4), 646; https://doi.org/10.3390/antibiotics12040646
Submission received: 23 February 2023 / Revised: 16 March 2023 / Accepted: 21 March 2023 / Published: 24 March 2023
(This article belongs to the Special Issue Antimicrobial Stewardship and Prescribing Practice)
Browse Figures
Review Reports Versions Notes

Abstract

:
There are concerns with excessive antibiotic prescribing among patients admitted to hospital with COVID-19, increasing antimicrobial resistance (AMR). Most studies have been conducted in adults with limited data on neonates and children, including in Pakistan. A retrospective study was conducted among four referral/tertiary care hospitals, including the clinical manifestations, laboratory findings, the prevalence of bacterial co-infections or secondary bacterial infections and antibiotics prescribed among neonates and children hospitalized due to COVID-19. Among 1237 neonates and children, 511 were admitted to the COVID-19 wards and 433 were finally included in the study. The majority of admitted children were COVID-19-positive (85.9%) with severe COVID-19 (38.2%), and 37.4% were admitted to the ICU. The prevalence of bacterial co-infections or secondary bacterial infections was 3.7%; however, 85.5% were prescribed antibiotics during their hospital stay (average 1.70 ± 0.98 antibiotics per patient). Further, 54.3% were prescribed two antibiotics via the parenteral route (75.5%) for ≤5 days (57.5), with most being ‘Watch’ antibiotics (80.4%). Increased antibiotic prescribing was reported among patients requiring mechanical ventilation and high WBCs, CRP, D-dimer and ferritin levels (p < 0.001). Increased COVID-19 severity, length of stay and hospital setting were significantly associated with antibiotic prescribing (p < 0.001). Excessive antibiotic prescribing among hospitalized neonates and children, despite very low bacterial co-infections or secondary bacterial infections, requires urgent attention to reduce AMR.

1. Introduction

In Pakistan, cases of COVID-19 have now been reported in almost every geographical location of the country and across all age groups. In Lahore, 19,367 children between the ages of 1 and 18 had been affected with COVID-19 between March 2020 and March 2021 [1], and in Islamabad, 5792 children up to 10 years of age had tested positive for COVID-19 from the start of the pandemic until April 2021 [2].
An early study from Karachi indicated that among children admitted with COVID-19, 26% of the cases were moderate and 12% severe, with a mortality rate of 7%, principally among those with severe disease [3]. A World Health Organization (WHO)-sponsored study also showed high mortality rates (up to 14%) among children in Pakistan admitted with moderate-to-severe COVID-19 during the early stages of the pandemic [4].
Whilst children typically have lower infection rates with COVID-19 than adults, alongside milder symptoms [5,6,7,8], up to 10% of children admitted to hospital with COVID-19 experienced severe disease. Up to 20% or more of admitted children were subsequently admitted to pediatric intensive care units (PICUs) [5,9,10,11]. Viral pneumonia was the commonest presenting condition [10,12,13]. However, there are concerns with children developing Kawasaki Disease (KD)-like symptoms, now known as Pediatric Inflammatory Multisystem Syndrome (PIMS-TS), alongside experiencing coagulation disorders as well as respiratory changes and abdominal involvement with COVID-19 [14,15,16,17,18,19,20]. These combined symptoms increase admission to (PICUs). Admission to PICUs is an issue in lower- and middle-income countries (LMICs) versus higher-income countries, with more limited healthcare resources and deaths among these hospitalized children [11]. This was reflected by the high mortality rates (40%) among pediatric patients admitted to Dr. Cipto Mangunkusumo Hospital in Indonesia at the start of the COVID-19 pandemic, before improvements in knowledge and possible treatments [21]. Admission to ICUs is a concern among patients with COVID-19, as they can develop fungal or bacterial co-infections, increasing mortality and hospital length of stay [22,23].
Whilst local health authorities in Pakistan and others have supported the prescribing of antibiotics in patients with COVID-19 with secondary bacterial or bacterial co-infections [10,24,25,26,27,28], their excessive use is common among patients across countries hospitalized with COVID-19, including children, especially with concerns with pneumonia and the implications [9,10,29,30,31]. This is despite only a limited number of patients actually having secondary bacterial or bacterial co-infections in practice [29,31,32]. These prescribing habits have not been helped by some national guidelines advocating the empiric prescribing of antibiotics along with hydroxychloroquine in patients with COVID-19, despite limited evidence of benefit [12,33,34,35]. Published studies have also documented appreciable prescribing of antibiotics in patients with COVID-19 in Pakistan, again, despite limited evidence of bacterial co-infections and secondary bacterial infections [23,36,37,38,39].
Excessive prescribing of antibiotics is a concern, as their inappropriate and unjustified use increases antimicrobial resistance (AMR) [40,41,42,43,44,45]. Increasing AMR appreciably increases morbidity, mortality and costs, and has been described as the next pandemic unless addressed [42,46,47,48,49]. This is a key issue in patients with COVID-19, as AMR rates are increasing with an appreciable number of inappropriate prescriptions [50,51,52]. Consequently, these inappropriate prescribing habits need to be curtailed where possible. This is particularly important in Pakistan, which is currently the third largest consumer of antibiotics worldwide, with an appreciable increase in antibiotic use in recent years [53]. Alongside this, both multi-drug resistance (MDR) and extensive drug resistance (XDR) bacteria have been seen in different regions of Pakistan [54,55,56,57,58,59].
A number of published studies from Pakistan have highlighted appreciable prescribing of antibiotics in adult hospitalized patients with COVID-19. This is despite the limited prevalence of bacterial co-infections or secondary bacterial infections [37,38,39]. In addition, there has been considerable prescribing of ‘Watch’ and ‘Reserve’ antibiotics from the WHO AWaRe list. This is important as the antibiotics from the ‘Watch’ and ‘Reserve’ list have a greater resistance potential than those from the ‘Access’ list [41,60]. Their prescribing in Pakistan needs to be appreciably reduced to achieve a suggested target of 60% ‘access’ antibiotics being prescribed [37,38,39,60]. However, we are unaware of any studies that have been conducted among neonates and children in Pakistan to investigate the current utilization patterns in this group. This is important given concerns with mortality rates among children with COVID-19 admitted initially to hospitals in Pakistan, as well concerns generally with children admitted to PICUs in LMICs with COVID-19 [3,11].
Consequently, the aims of this study were to thoroughly investigate the clinical manifestations and laboratory findings of neonates and children admitted to hospitals in Pakistan with COVID-19. Secondly, to investigate the prevalence of bacterial co-infections and secondary bacterial infections, alongside the extent of antibiotic prescribing among this population hospitalized in Pakistan due to COVID-19. Subsequently, to use the findings to guide future strategies in Pakistan if there is excessive prescribing of antibiotics, especially ‘Watch’ and ‘Reserve’ antibiotics.

2. Results

A total of 1237 neonates and children were seen in the emergency rooms of participating hospitals between March 2022 and December 2022. Among these children, 511 were admitted to the COVID-19 wards. Seventy-eight cases were subsequently excluded due to incomplete medical records. This left a final sample of 433 children (Figure 1).
The demographic details of the children are shown in Table 1. Most of the study population were children aged 5 to 12 years (45%), followed by those aged 1 to 5 years (33.7%), and 64% were male children. Of the admitted children, 85.9% were COVID-19-positive, with 14.1% suspected cases. Suspected cases included children who were not currently testing positive; however, their parents had seen signs and symptoms of COVID-19. In addition, these children had at least one family member diagnosed with COVID-19.
As far as disease severity is concerned, 4.8% of cases were asymptomatic, 21.5% had mild disease, 26.9% had moderate disease, 38.2% had severe disease and 8.6% were critical cases. Of the children, 37.4% were admitted to the ICU, with 2.8% requiring mechanical ventilation. Fever was one of the common symptoms among the study population, present in 71.8% of children, followed by a cough (66.1%) and tachypnea (62.1%). X-ray abnormalities were reported in 81.1% of the children and 65.1% had elevated WBCs (Table 1). More than half (52.4%) of the study population required hospitalization between 8 and 14 days.
Figure 2 shows all the medication prescribed to the study population. Besides antibiotics, the three most commonly prescribed treatments were intravenous fluids and/or inhalation fluids (85.5%), antipyretics (61.7%) and corticosteroids (55.9%).
A total of 370 (85.5%) neonates and children were prescribed antibiotics during their hospital stay, with 736 antibiotics prescribed among them (average 1.70 ± 0.98 antibiotics per patient; Table 2). More than half (54.3%) of the children were prescribed two antibiotics, followed by 24.9% with one, and 20.8% of the children were prescribed three antibiotics (Table 2). The majority of the antibiotics (75.5%) were administered parenterally. More than half of the antibiotics were prescribed for ≤5 days, and 39.4% for 6–10 days.
Antibiotics prescribed according to the ATC class and subclass are shown in the Table 3. Third-generation cephalosporins and macrolides were the most commonly prescribed classes of antibiotics. The top three most commonly prescribed antibiotics were azithromycin (n = 183), ceftriaxone (n = 173) and meropenem (n = 74).
Antibiotic usage grouped according to the AWaRe classification are shown in Figure 3. Most of the prescribed antibiotics were from the ‘Watch’ group (80.4%, n = 592). Only 16.7% (n = 123) of the prescribed antibiotics were from the ‘Access’ group.
A comparison of antibiotic usage between the demographic and clinical variables are shown in Table 4. A significant difference regarding the extent and nature of antibiotics prescribed was observed among the different hospitals (p = 0.001).
In a post hoc analysis (Table 5), the prescribing of antibiotics was significantly higher among neonates and children in Hospital 2 compared to those in Hospitals 3 and 4. As anticipated, antibiotic prescribing was substantially higher in COVID-19-positive patients, with an increasing number of antibiotics prescribed with increasing severity of COVID-19 (Table 4). Increased antibiotic prescribing was also observed among patients requiring mechanical ventilation, as well as those with elevated WBCs, CRP, D-dimer and ferritin levels (Table 4).
A multiple linear regression analysis was performed to confirm all the factors linked with antibiotic prescribing among admitted children (Table 6). Increased COVID-19 severity, hospital length of stay and the hospital setting were found to be significantly associated with antibiotic prescribing.
As far as outcomes are concerned, 3.2% children died during the study period, whereas 96.8% were discharged from the participating hospitals.
Bacterial culture testing was ordered for 28 patients. Of these, 12 came back negative and 16 patients had identified bacterial pathogens. Consequently, the confirmed prevalence of bacterial or secondary bacterial infections was 3.7% (Figure 4).
Details of culture and sensitivity testing are provided in Table 7. The most common bacterial pathogens identified in our study sample were Pseudomonas aeruginosa (n = 9, 32.1%) and Streptococcus pneumoniae (n = 3, 10.7%).

3. Discussion

We believe this is one of the first studies conducted among neonates and children hospitalized in Pakistan due to suspected or confirmed COVID-19. This includes the clinical manifestations and laboratory findings of admitted children, the prevalence of bacterial co-infections and the subsequent management of children, including any prescribing of antimicrobials during their stay in hospitals. There was a lower prevalence of COVID-19 among admitted neonates and infants in this study compared with children in the higher age groups. This is similar to the findings in Ghana and India, as well as in the USA [9,12,61]. However, this is different to the findings from a study in Bangladesh, where the majority of admitted children were aged 0 to 5 years [10]. The low prevalence of COVID-19 in neonates and infants might be associated with low transmission levels in this age group, due to greater immobility. However, we cannot say this with certainty.
The majority of admitted neonates and children in this study were COVID-19-positive and without co-morbidities, similar to findings from Ghana, Italy and India [9,12,62]. In addition, children were typically admitted with moderate-to-severe disease rather than asymptomatic or mild disease. This is similar to the findings of studies in Ghana, Iran and the USA [12,63,64]; however, different from a study in Saudi Arabia with very young infants (≤90 days), and Qatar, where thresholds for admitting children were lower than for adults, as well as in a study from Turkey [65,66,67]. The higher prevalence of severe and critical COVID-19 children reported in our study may be associated with the fact that we conducted this study among four referral/teachings hospitals, with mild cases likely to be treated in primary or secondary care hospitals in the province.
More than one third of our study population was admitted to the ICU, with the most common symptoms among them being fever, cough and tachypnoea. This is similar to the US (25.5% admitted to ICU), as well as a systematic review comparing LMICs to higher-income countries [68,69]. However, our findings are different from studies in Bangladesh (13.7%), India (22.2%), Spain (19.7%) and the UK (4.1%) in terms of children admitted to ICU with COVID-19 [9,10,70,71]. The potential reasons for the high ICU admission in our study could again be referrals to these specialist hospitals. The symptoms of fever, cough and tachypnoea, typical of viral pneumonia, were similar through to other studies undertaken with children across countries [9,10,72,73,74]. X-ray abnormalities were one of the most frequent laboratory findings, followed by out-of-range WBCs and CRP in our study, which is similar to other published studies documenting changes in chest X-rays in patients with COVID-19 [3,74,75,76]. However, other authors found different findings [67]. We are not sure of the reasons behind the different findings between the studies. This may be due to differences in admittance criteria; however, we are not sure.
There was appreciable prescribing of antibiotics among the neonates and children hospitalized with COVID19 in our study at >85%, with more than half being prescribed two antibiotics. In addition, nearly one-quarter of admitted patients were prescribed three different antibiotics during their hospital stay, with an average of 1.70 ± 0.98 antibiotics per patient. This is despite only 3.7% of neonates and children having confirmed bacterial co-infections or secondary bacterial infections. However, similarly high rates of antibiotic prescribing were seen in our previous study among all hospitalized neonates and children conducted between 10 December 2021 and 5 January 2022 [13], similar to studies undertaken in Bangladesh (86.3%) and India (75.3%) [9,10]. The prescribing of antibiotics in our study was though higher than seen in studies in Latin America (24.5%) and Turkey [67,77]. In addition, more than half of the antibiotics prescribed in our study were for ≤5 days and via parenteral route of administration. This is similar to a study from Spain, where the majority of the antibiotics administered were prescribed for <5 days among children hospitalized with COVID-19 [71].
Of equal concern is that 80.4% of the prescribed antibiotics were from the WHO ‘Watch’ category, increasing resistance rates [41]. This is similar though to the high rates of prescribing of ‘Watch’ antibiotics among children in Bangladesh and India [9,10]. These high rates need to be urgently addressed, given the already rising rates of AMR in Pakistan, and ongoing challenges to reduce this as part of their national action plan to reduce AMR [78,79]. We are seeing antimicrobial stewardship programs (ASPs) being successfully introduced among hospitals across LMICs to improve appropriate antibiotic prescribing despite initial concerns, and these can serve as exemplars for Pakistan in the future [44,45,80,81,82,83]. We will be following this up in future studies now that the AWaRe book has been published, providing guidance for a range of infections, combined with suggested prescribing and quality indicators [60,84].
The mortality rate of 3.2% seen in our study is lower than earlier studies in Pakistan involving children, which is encouraging [3,4]. This may reflect improved knowledge with treating children with COVID-19, with similar findings in other countries [10,85].
We are aware of a number of limitations with our study. Firstly, we only collected data from referral/tertiary care hospitals in the Punjab Province. Secondly, we did not use a validated data collection form. However, this was based on an appreciable number of published papers, as well as the experience of the co-authors in similar studies across countries, building on an earlier study involving neonates and children in Pakistan. Thirdly, we did not include any data on the use of anti-fungal medicines in our study despite ICU patients potentially having both fungal and bacterial infections. This is because we wanted to principally concentrate on antibiotic prescribing given increasing AMR rates in Pakistan, and the consequences. Lastly, we did not contact patients directly, and only collected data from the patients’ medical records. However, this is similar to all retrospective studies in hospitals, including point-prevalence surveys. Despite these limitations, we believe our findings are robust, providing direction to key stakeholder groups in Pakistan involved in managing neonates and children with COVID-19, especially surrounding the inappropriate prescribing of antibiotics.

4. Materials and Methods

4.1. General Outline of the Study

A retrospective, medical records review study was conducted in the COVID-19 wards among four tertiary care hospitals in the Punjab Province, designated for the management of children suspected or diagnosed with COVID-19. Since the emergence of COVID-19 and identification of very first case of laboratory confirmed COVID-19 in the country, these hospitals have served as the referral hospitals for the province for the management of children with COVID-19, up to the age of 12 years.
Punjab was selected for this study because it is the most populus province in Pakistan, with a number of previous studies undertaken by the co-authors in the province, including patients with COVID-19, serving as comparators [23,39,86,87,88,89,90]. Moreover, these tertiary care/teaching hospitals were equipped with adequate medical personnel, laboratory facilities and personal protective equipment, as well as medicines for the effective management of children admitted with COVID-19. Tertiary care hospitals were selected for the current study because they are likely to provide guidance to the primary and secondary care hospitals in this province and across Pakistan.

4.2. Study Variables

Based on previous studies [10,12,23,37,38,39,89,90,91,92], data on the following variables were collected from the medical records of hospitalized neonates and children suspected or confirmed with COVID-19:
  • Demographic characteristics of the study participants, including their age, gender, residence, number of days at the hospital, admission to the intensive care unit, presence of any co-morbidity, and the use of ventilation during hospital stays.
  • Status of COVID-19 was documented by the investigators. A positive or confirmed COVID-19 patient is defined as a positive result on a real-time reverse-transcriptase polymerase chain reaction (PCR) assay of nasal or pharyngeal swab specimens. As mentioned, suspected cases included children who were not currently testing positive; however, their parents had seen signs and symptoms of COVID-19. In addition, these children had at least one family member diagnosed with COVID-19.
  • COVID-19 disease severity, categorized into asymptomatic, mild, moderate, severe and critical, as per the guidelines for the management of COVID-19 issued by the Ministry of National Health Services, Regulation, and Coordination, Government of Pakistan. Asymptomatic cases meant children were tested as positive with COVID-19; however, were currently without symptoms. Mild cases include those manifesting symptoms due to COVID-19, but without hemodynamic disturbances and X-ray abnormalities. Mild cases did not require oxygen and the oxygen saturation in mild cases must be ≥94%. Those patients that had abnormal chest X-rays, including X-rays infiltrates involving <50% of the total lung fields, oxygen saturation below 94%, but above 90%, and without any severe symptoms, were declared as moderate cases of COVID-19. Severe cases of COVID-19 included children that had a fever and cough along with respiratory rate < 30, severe respiratory distress, chest X-rays with infiltrates involving <50% of the total lung fields and oxygen saturation ≤ 90 on room air. Critical cases were those that showed a worsening of respiratory symptoms or the presence of acute respiratory distress syndrome (ARSD), respiratory or cardiac failure and bilateral opacities or lung collapse on chest X-rays or CT scans.
  • Signs and symptoms of COVID-19 including a fever, cough, sore throat, tachypnea, deceases level of consciousness, headache/body ache, lethargy, nausea, vomiting, diarrhea, and irritability, were documented from individual medical records.
  • Laboratory findings, including white blood cell counts (WBCs), c-reactive protein (CRP) level, D-dimer, and serum ferritin, were recorded by the investigators in patients’ notes. X-ray findings were reviewed by the medical doctors and consulted with treating physicians in case any clarification was needed. Normal ranges of WBCs, CRP D-dimer and serum ferritin were taken from the reference mentioned in the testing kits that were available and used in the laboratories of the participating hospitals.
  • Existence of bacterial co-infection and secondary bacterial infection among COVID-19 patients. Bacterial co-infection was identified as those bacterial infections identified in ≤2 days after hospital admission due to COVID-19 and bacterial secondary infection as bacterial infections identified in >2 days after admission, confirmed microbiologically.
  • Details about the antibiotics prescribed among hospitalized neonates and children. This included how many hospitalized COVID-19 patients were prescribed antibiotics during their stay in hospitals, as well as the existence of bacterial co-infection and bacterial secondary infections. Antibiotics were further classified according to the ATC classification, as well as the WHO AWaRe classification [60,93,94]. ‘Access’ antibiotics should typically be prescribed to treat commonly encountered infections, as they have a lower resistance potential, with those in the ‘Watch’ group ideally only prescribed in critical conditions, as they have a greater chance of resistance development. Those in the ‘Reserve’ category should only be prescribed in multi-drug resistance cases, with the aim of curbing rising AMR rates [41,60,84,94,95,96].
  • The total number of antibiotics, the average number of antibiotics prescribed per patient, the duration of antibiotic therapy and the consumption of other antimicrobials. We did not specifically document the extent of prescribing of antifungals, although we are aware that there can be joint fungal and bacterial co-infections in patients in the ICU [22], as our main focus was on the extent of the prescribing of antibiotics, especially ‘Watch’ antibiotics in this population, alongside the extent of bacterial infections, including secondary bacterial infections.
  • Outcomes, including whether neonates or children were discharged from a hospital or died.

4.3. Inclusion and Exclusion Criteria and Data Collection Procedures

Inclusion criteria included neonates and children ≤ 12 years age admitted to the COVID-19 wards, including intensive care units, among the four referral hospitals in Punjab, with suspected or proven COVID-19 and having complete medical records available at the hospital record room.
All neonates and children admitted in other wards of the designated hospitals diagnosed with illnesses other than COVID-19 or having incomplete medical records were excluded from this study.
The team of investigators comprised pharmacists, medical doctors, nurses, pharmacy and laboratory technicians. The investigators visited the record rooms for the COVID-19 wards in the participating hospitals and thoroughly searched the files to collect the necessary information. All the medical records were paper-based in these hospitals.

4.4. Statictical Analyses

Continuous data were reported as the mean ± standard deviation, whereas categorical data were reported as the number (N) and/or percentage (%). Antibiotic use was compared among demographic and clinical variables using an independent t-test and ANOVA, where applicable. Furthermore, post hoc analyses were performed to determine potential differences between three or more groups when the ANOVA test yielded significant results. Multiple logistic regression analyses were also performed to determine factors linked with antibiotic use in children hospitalized with COVID-19 (method: stepwise). All data analysis were performed in SPSS version 22 for Microsoft windows.

4.5. Ethical Considerations

Ethical approval for the study was obtained from the Human Research Ethics Committee, Department of Pharmacy Practice, The University of Lahore (REC/DPP/FOP/49). Moreover, permission to conduct the study in the different hospitals was obtained from the administrators/ethic committee of each hospital prior to data collection. No personal patient information was collected at any stage of data collection.
The confidentiality of the data was ensured by the allocation of anonymized identifier to every patient, which was separated from the data, for the purpose of verifying the accuracy of the recorded data. Institutional ethics committee allowed the investigators to collect data without patient consent, as this was a retrospective study with no direct contact with the patients and/or their parents.

5. Conclusions

Overall, neonates and children admitted to tertiary hospitals in Pakistan due to COVID-19 were excessively prescribed antibiotics, despite very low prevalence of bacterial co-infections. Of equal concern was that the vast majority of prescribed antibiotics was from the ‘Watch’ category, potentially worsening AMR. This needs to be urgently addressed across Pakistan, with the appropriate implementation of ASPs.

Author Contributions

Z.U.M., A.H.K. and B.G. were involved with the conceptualization of the study and the methodology. Z.U.M. and B.G. provided the background for the study and assisted with the methodology, Z.U.M., A.H.K., S.N.H. and M.S. were involved with data collection, its analysis and validation. Z.U.M., A.H.K., S.N.H., M.S. and B.G. assisted with the analysis and interpretation of the data. Z.U.M. and B.G. produced the first paper of the paper with all authors reviewing subsequent drafts before submission. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

Ethical approval for the study was obtained from the Human Research Ethics Committee, Department of Pharmacy Practice, The University of Lahore (REC/DPP/FOP/49). Moreover, permission to conduct the study in the different hospitals was obtained from the administrators/ethic committee of each hospital prior to data collection. No personal patient information was collected at any stage of data collection.

Informed Consent Statement

No informed consent was sought since, as mentioned, there was no direct contact with patients or their guardians. The data collected were obtained directly from patients’ medical records and the data were anonymized. This is in line with other similar studies undertaken by the co-authors [9,10,97,98,99,100,101,102].

Data Availability Statement

Further data are available on reasonable request from the corresponding authors.

Acknowledgments

We are grateful to the administration and healthcare providers of the participant hospitals for their support in the data collection and interpretation of this project.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Ahmed, T.; Ilyas, M.; Yousafzai, W. COVID-19 in Children Rattles Healthcare-Hospitals in Three Major Cities Suspect Higher Number of Coronavirus Cases in Minors. 2021. Available online: https://tribune.com.pk/story/2293275/covid-19-in-children-rattles-healthcare (accessed on 10 February 2023).
  2. The Express Tribune. At Least 5792 Children Tested Positive for COVID-19 in Islamabad. 2021. Available online: https://tribune.com.pk/story/2292667/at-least-5792-children-tested-positive-for-covid-19-in-islamabad (accessed on 8 February 2023).
  3. Shahid, S.; Raza, M.; Junejo, S.; Maqsood, S. Clinical features and outcome of COVID-19 positive children from a tertiary healthcare hospital in Karachi. J. Med. Virol. 2021, 93, 5988–5997. [Google Scholar] [CrossRef] [PubMed]
  4. Latif, A. Pakistani Children Face 14% Mortality Risk after Catching COVID: Study. 2021. Available online: https://www.aa.com.tr/en/asia-pacific/pakistani-children-face-14-mortality-risk-after-catching-covid-study/2445719# (accessed on 8 February 2023).
  5. Bhuiyan, M.U.; Stiboy, E.; Hassan, M.Z.; Chan, M.; Islam, M.S.; Haider, N.; Jaffe, A.; Homaira, N. Epidemiology of COVID-19 infection in young children under five years: A systematic review and meta-analysis. Vaccine 2021, 39, 667–677. [Google Scholar] [CrossRef]
  6. Cui, X.; Zhao, Z.; Zhang, T.; Guo, W.; Guo, W.; Zheng, J.; Zhang, J.; Dong, C.; Na, R.; Zheng, L.; et al. A systematic review and meta-analysis of children with coronavirus disease 2019 (COVID-19). J. Med. Virol. 2020, 93, 1057–1069. [Google Scholar] [CrossRef] [PubMed]
  7. Ma, X.; Liu, S.; Chen, L.; Zhuang, L.; Zhang, J.; Xin, Y. The clinical characteristics of pediatric inpatients with SARS-CoV-2 infection: A meta-analysis and systematic review. J. Med. Virol. 2021, 93, 234–240. [Google Scholar] [CrossRef] [PubMed]
  8. Howard-Jones, A.R.; Bowen, A.C.; Danchin, M.; Koirala, A.; Sharma, K.; Yeoh, D.K.; Burgner, D.P.; Crawford, N.W.; Goeman, E.; Gray, P.E.; et al. COVID-19 in children: I. Epidemiology, prevention and indirect impacts. J. Paediatr. Child Health 2021, 58, 39–45. [Google Scholar] [CrossRef]
  9. Kumar, S.; Haque, M.; Shetty, A.; Choudhary, S.; Bhatt, R.; Sinha, V.; Manohar, B.; Chowdhury, K.; Nusrat, N.; Jahan, N.; et al. Characteristics and Management of Children With Suspected COVID-19 Admitted to Hospitals in India: Implications for Future Care. Cureus 2022, 14, e27230. [Google Scholar] [CrossRef]
  10. Chowdhury, K.; Haque, M.; Nusrat, N.; Adnan, N.; Islam, S.; Lutfor, A.B.; Begum, D.; Rabbany, A.; Karim, E.; Malek, A.; et al. Management of Children Admitted to Hospitals across Bangladesh with Suspected or Confirmed COVID-19 and the Implications for the Future: A Nationwide Cross-Sectional Study. Antibiotics 2022, 11, 105. [Google Scholar] [CrossRef]
  11. Irfan, O.; Muttalib, F.; Tang, K.; Jiang, L.; Lassi, Z.S.; Bhutta, Z. Clinical characteristics, treatment and outcomes of paediatric COVID-19: A systematic review and meta-analysis. Arch. Dis. Child. 2021, 106, 440–448. [Google Scholar] [CrossRef]
  12. Sefah, I.A.; Sarkodie, S.A.; Pichierri, G.; Schellack, N.; Godman, B. Assessing the Clinical Characteristics and Management of COVID-19 among Pediatric Patients in Ghana: Findings and Implications. Antibiotics 2023, 12, 283. [Google Scholar] [CrossRef]
  13. Mustafa, Z.U.; Khan, A.H.; Salman, M.; Sulaiman, S.A.S.; Godman, B. Antimicrobial Utilization among Neonates and Children: A Multicenter Point Prevalence Study from Leading Children’s Hospitals in Punjab, Pakistan. Antibiotics 2022, 11, 1056. [Google Scholar] [CrossRef]
  14. Mantovani, A.; Rinaldi, E.; Zusi, C.; Beatrice, G.; Saccomani, M.D.; Dalbeni, A. Coronavirus disease 2019 (COVID-19) in children and/or adolescents: A meta-analysis. Pediatr. Res. 2020, 89, 733–737. [Google Scholar] [CrossRef] [PubMed]
  15. Mardi, P.; Esmaeili, M.; Iravani, P.; Abdar, M.E.; Pourrostami, K.; Qorbani, M. Characteristics of Children With Kawasaki Disease-Like Signs in COVID-19 Pandemic: A Systematic Review. Front. Pediatr. 2021, 9, 625377. [Google Scholar] [CrossRef] [PubMed]
  16. Shahriarirad, R.; Dashti, A.S.; Ghotbabadi, S.H. Multisystem Inflammatory Syndrome with Features of Atypical Kawasaki Disease during the COVID-19 Pandemic. Case Rep. Pediatr. 2021, 2021, 1–4. [Google Scholar] [CrossRef] [PubMed]
  17. Yasuhara, J.; Watanabe, K.; Takagi, H.; Sumitomo, N.; Kuno, T. COVID-19 and multisystem inflammatory syndrome in children: A systematic review and meta-analysis. Pediatr. Pulmonol. 2021, 56, 837–848. [Google Scholar] [CrossRef] [PubMed]
  18. Hobbs, C.V.; Khaitan, A.; Kirmse, B.M.; Borkowsky, W. COVID-19 in Children: A Review and Parallels to Other Hyperinflammatory Syndromes. Front. Pediatr. 2020, 8, 593455. [Google Scholar] [CrossRef]
  19. Tiwari, A.; Balan, S.; Rauf, A.; Kappanayil, M.; Kesavan, S.; Raj, M.; Sivadas, S.; Vasudevan, A.K.; Chickermane, P.; Vijayan, A.; et al. COVID-19 related multisystem inflammatory syndrome in children (MIS-C): A hospital-based prospective cohort study from Kerala, India. BMJ Paediatr. Open 2021, 5, e001195. [Google Scholar] [CrossRef]
  20. Brandi, N.; Ciccarese, F.; Rimondi, M.R.; Balacchi, C.; Modolon, C.; Sportoletti, C.; Renzulli, M.; Coppola, F.; Golfieri, R. An Imaging Overview of COVID-19 ARDS in ICU Patients and Its Complications: A Pictorial Review. Diagnostics 2022, 12, 846. [Google Scholar] [CrossRef]
  21. Dewi, R.; Kaswandani, N.; Karyanti, M.R.; Setyanto, D.B.; Pudjiadi, A.H.; Hendarto, A.; Djer, M.M.; Prayitno, A.; Yuniar, I.; Indawati, W.; et al. Mortality in children with positive SARS-CoV-2 polymerase chain reaction test: Lessons learned from a tertiary referral hospital in Indonesia. Int. J. Infect. Dis. 2021, 107, 78–85. [Google Scholar] [CrossRef]
  22. Bardi, T.; Pintado, V.; Gomez-Rojo, M.; Escudero-Sanchez, R.; Lopez, A.A.; Diez-Remesal, Y.; Castro, N.M.; Ruiz-Garbajosa, P.; Pestaña, D. Nosocomial infections associated to COVID-19 in the intensive care unit: Clinical characteristics and outcome. Eur. J. Clin. Microbiol. Infect. Dis. 2021, 40, 495–502. [Google Scholar] [CrossRef]
  23. Mustafa, Z.U.; Tariq, S.; Iftikhar, Z.; Meyer, J.C.; Salman, M.; Mallhi, T.H.; Khan, Y.H.; Godman, B.; Seaton, R.A. Predictors and Outcomes of Healthcare-Associated Infections among Patients with COVID-19 Admitted to Intensive Care Units in Punjab, Pakistan; Findings and Implications. Antibiotics 2022, 11, 1806. [Google Scholar] [CrossRef]
  24. WHO. Clinical Management of COVID-19: Living Guideline, 15 September 2022. Available online: https://www.who.int/publications/i/item/WHO-2019-nCoV-Clinical-2022.2 (accessed on 8 February 2023).
  25. Ministry of National Health Services Regulations and Coordination, Government of Pakistan. Guidelines-Management of COVID19 in Children 2020. Available online: https://www.childhealthtaskforce.org/sites/default/files/2021-04/Pakistan%20Ministry%20of%20National%20Health%20Services%2C%20Management%20of%20COVID-19%20in%20Children.pdf (accessed on 7 February 2023).
  26. NICE. COVID-19 Rapid Guideline: Managing COVID-19. 2022. Available online: https://www.nice.org.uk/guidance/ng191/resources/covid19-rapid-guideline-managing-covid19-pdf-51035553326 (accessed on 8 January 2023).
  27. National Institutes of Health. COVID-19 Treatment Guidelines; Anti-SARS-CoV-2 Antibody Products. 2022. Available online: https://www.covid19treatmentguidelines.nih.gov/ (accessed on 17 January 2022).
  28. Langford, B.J.; So, M.; Raybardhan, S.; Leung, V.; Soucy, J.-P.R.; Westwood, D.; Daneman, N.; MacFadden, D.R. Antibiotic prescribing in patients with COVID-19: Rapid review and meta-analysis. Clin. Microbiol. Infect. 2021, 27, 520–531. [Google Scholar] [CrossRef]
  29. Alshaikh, F.S.; Godman, B.; Sindi, O.N.; Seaton, R.A.; Kurdi, A. Prevalence of bacterial coinfection and patterns of antibiotics prescribing in patients with COVID-19: A systematic review and meta-analysis. PLoS ONE 2022, 17, e0272375. [Google Scholar] [CrossRef] [PubMed]
  30. Khan, S.; Hasan, S.S.; Bond, S.E.; Conway, B.R.; Aldeyab, M.A. Antimicrobial consumption in patients with COVID-19: A systematic review and meta-analysis. Expert Rev. Anti-Infect. Ther. 2021, 20, 749–772. [Google Scholar] [CrossRef] [PubMed]
  31. Langford, B.J.; So, M.; Raybardhan, S.; Leung, V.; Westwood, D.; MacFadden, D.R.; Soucy, J.-P.R.; Daneman, N. Bacterial co-infection and secondary infection in patients with COVID-19: A living rapid review and meta-analysis. Clin. Microbiol. Infect. 2020, 26, 1622–1629. [Google Scholar] [CrossRef] [PubMed]
  32. Lansbury, L.; Lim, B.; Baskaran, V.; Lim, W.S. Co-infections in people with COVID-19: A systematic review and meta-analysis. J. Infect. 2020, 81, 266–275. [Google Scholar] [CrossRef]
  33. Adebisi, Y.A.; Jimoh, N.D.; Ogunkola, I.O.; Uwizeyimana, T.; Olayemi, A.H.; Ukor, N.A.; Lucero-Prisno, D.E. The use of antibiotics in COVID-19 management: A rapid review of national treatment guidelines in 10 African countries. Trop. Med. Health 2021, 49, 1–5. [Google Scholar] [CrossRef]
  34. Republic of Ghana Ministry of Health. Provisional Standard Treatment Guidelines for Novel Coronavirus Infection: COVID-19 Guidelines for Ghana. 2020. Available online: https://www.moh.gov.gh/wp-content/uploads/2016/02/COVID-19-STG-JUNE-2020-1.pdf (accessed on 10 January 2023).
  35. RECOVERY Collaborative Group; Horby, P.; Mafham, M.; Linsell, L.; Bell, J.L.; Staplin, N.; Emberson, J.R.; Wiselka, M.; Ustianowski, A.; Elmahi, E.; et al. Effect of Hydroxychloroquine in Hospitalized Patients with COVID-19. N. Engl. J. Med. 2020, 383, 2030–2040. [Google Scholar] [CrossRef]
  36. Hayat, K.; Mustafa, Z.U.; Ikram, M.N.; Ijaz-Ul-Haq, M.; Noor, I.; Rasool, M.F.; Ishaq, H.M.; Rehman, A.U.; Hasan, S.S.; Fang, Y. Perception, Attitude, and Confidence of Physicians About Antimicrobial Resistance and Antimicrobial Prescribing Among COVID-19 Patients: A Cross-Sectional Study From Punjab, Pakistan. Front. Pharmacol. 2022, 12. [Google Scholar] [CrossRef]
  37. Ramzan, K.; Shafiq, S.; Raees, I.; Mustafa, Z.U.; Salman, M.; Khan, A.H.; Meyer, J.C.; Godman, B. Co-Infections, Secondary Infections, and Antimicrobial Use in Patients Hospitalized with COVID-19 during the First Five Waves of the Pandemic in Pakistan; Findings and Implications. Antibiotics 2022, 11, 789. [Google Scholar] [CrossRef]
  38. Mustafa, Z.U.; Saleem, M.S.; Ikram, M.N.; Salman, M.; Butt, S.A.; Khan, S.; Godman, B.; Seaton, R.A. Co-infections and antimicrobial use among hospitalized COVID-19 patients in Punjab, Pakistan: Findings from a multicenter, point prevalence survey. Pathog. Glob. Health 2021, 116, 421–427. [Google Scholar] [CrossRef]
  39. Ul Mustafa, Z.; Salman, M.; Aldeyab, M.; Kow, C.S.; Hasan, S.S. Antimicrobial consumption among hospitalized patients with COVID-19 in Pakistan. SN Compr. Clin. Med. 2021, 3, 1691–1695. [Google Scholar] [CrossRef] [PubMed]
  40. World Health Organization. No Time to Wait: Securing the Future from Drug-Resistant Infections. 2019. Available online: https://www.who.int/publications/i/item/no-time-to-wait-securing-the-future-from-drug-resistant-infections (accessed on 10 January 2023).
  41. Sulis, G.; Sayood, S.; Katukoori, S.; Bollam, N.; George, I.; Yaeger, L.H.; Chavez, M.A.; Tetteh, T.; Yarrabelli, S.; Pulcini, C.; et al. Exposure to World Health Organization’s AWaRe antibiotics and isolation of multidrug resistant bacteria: A systematic review and meta-analysis. Clin. Microbiol. Infect. 2022, 28, 1193–1202. [Google Scholar] [CrossRef]
  42. Dadgostar, P. Antimicrobial Resistance: Implications and Costs. Infect. Drug Resist. 2019, 12, 3903–3910. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  43. Abu Hammour, K.; Al-Heyari, E.; Allan, A.; Versporten, A.; Goossens, H.; Abu Hammour, G.; Manaseer, Q. Antimicrobial Consumption and Resistance in a Tertiary Care Hospital in Jordan: Results of an Internet-Based Global Point Prevalence Survey. Antibiotics 2020, 9, 598. [Google Scholar] [CrossRef]
  44. Godman, B.; Egwuenu, A.; Haque, M.; Malande, O.; Schellack, N.; Kumar, S.; Saleem, Z.; Sneddon, J.; Hoxha, I.; Islam, S.; et al. Strategies to Improve Antimicrobial Utilization with a Special Focus on Developing Countries. Life 2021, 11, 528. [Google Scholar] [CrossRef]
  45. Abdullah, S.; Rahman, S.U.; Muhammad, F.; Mohsin, M. Association between antimicrobial consumption and resistance rate of Escherichia coli in hospital settings. J. Appl. Microbiol. 2023, 134, lxac003. [Google Scholar] [CrossRef] [PubMed]
  46. Gautam, A. Antimicrobial Resistance: The Next Probable Pandemic. J. Nepal Med. Assoc. 2022, 60, 225–228. [Google Scholar] [CrossRef] [PubMed]
  47. Global burden of bacterial antimicrobial resistance in 2019: A systematic analysis. Lancet 2022, 399, 629–655. [CrossRef] [PubMed]
  48. OECD Health Policy Studies. Stemming the Superbug Tide. 2018. Available online: https://www.oecd-ilibrary.org/sites/9789264307599-en/index.html?itemId=/content/publication/9789264307599-en&mimeType=text/html (accessed on 8 January 2023).
  49. Cassini, A.; Högberg, L.D.; Plachouras, D.; Quattrocchi, A.; Hoxha, A.; Simonsen, G.S.; Colomb-Cotinat, M.; Kretzschmar, M.E.; Devleesschauwer, B.; Cecchini, M.; et al. Attributable deaths and disability-adjusted life-years caused by infections with antibiotic-resistant bacteria in the EU and the European Economic Area in 2015: A population-level modelling analysis. Lancet Infect. Dis. 2019, 19, 56–66. [Google Scholar] [CrossRef] [Green Version]
  50. Ghosh, S.; Bornman, C.; Zafer, M.M. Antimicrobial Resistance Threats in the emerging COVID-19 pandemic: Where do we stand? J. Infect. Public Health 2021, 14, 555–560. [Google Scholar] [CrossRef]
  51. Hsu, J. How COVID-19 is accelerating the threat of antimicrobial resistance. BMJ 2020, 369, m1983. [Google Scholar] [CrossRef]
  52. Iwu, C.J.; Jordan, P.; Jaja, I.F.; Iwu, C.D.; Wiysonge, C.S. Treatment of COVID-19: Implications for antimicrobial resistance in Africa. Pan Afr. Med. J. 2020, 35, 119. [Google Scholar] [CrossRef]
  53. Klein, E.Y.; Van Boeckel, T.P.; Martinez, E.M.; Pant, S.; Gandra, S.; Levin, S.A.; Goossens, H.; Laxminarayan, R. Global increase and geographic convergence in antibiotic consumption between 2000 and 2015. Proc. Natl. Acad. Sci. USA 2018, 115, E3463–E3470. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  54. Ullah, I.; Javaid, A.; Tahir, Z.; Ullah, O.; Shah, A.A.; Hasan, F.; Ayub, N. Pattern of Drug Resistance and Risk Factors Associated with Development of Drug Resistant Mycobacterium tuberculosis in Pakistan. PLoS ONE 2016, 11, e0147529. [Google Scholar] [CrossRef] [Green Version]
  55. Butt, M.H.; Saleem, A.; Javed, S.O.; Ullah, I.; Rehman, M.U.; Islam, N.; Tahir, M.N.; Malik, T.; Hafeez, S.; Misbah, S. Rising XDR-Typhoid Fever Cases in Pakistan: Are We Heading Back to the Pre-antibiotic Era? Front. Public Health 2021, 9, 794868. [Google Scholar] [CrossRef]
  56. Atif, M.; Mukhtar, S.; Sarwar, S.; Naseem, M.; Malik, I.; Mushtaq, A. Drug resistance patterns, treatment outcomes and factors affecting unfavourable treatment outcomes among extensively drug resistant tuberculosis patients in Pakistan; a multicentre record review. Saudi Pharm. J. 2022, 30, 462–469. [Google Scholar] [CrossRef] [PubMed]
  57. Bilal, H.; Khan, M.N.; Rehman, T.; Hameed, M.F.; Yang, X. Antibiotic resistance in Pakistan: A systematic review of past decade. BMC Infect. Dis. 2021, 21, 1–19. [Google Scholar] [CrossRef]
  58. Jabeen, F.; Khan, Z.; Sohail, M.; Tahir, A.; Tipu, I.; Murtaza Saleem, H.G. Antibiotic Resistance Pattern of Acinetobacter Baumannii Isolated From Bacteremia Patients in Pakistan. J. Ayub Med. Coll. Abbottabad. 2022, 34, 95–100. [Google Scholar] [PubMed]
  59. Javaid, N.; Sultana, Q.; Rasool, K.; Gandra, S.; Ahmad, F.; Chaudhary, S.U.; Mirza, S. Trends in antimicrobial resistance amongst pathogens isolated from blood and cerebrospinal fluid cultures in Pakistan (2011–2015): A retrospective cross-sectional study. PLoS ONE 2021, 16, e0250226. [Google Scholar] [CrossRef]
  60. Sharland, M.; Zanichelli, V.; Ombajo, L.A.; Bazira, J.; Cappello, B.; Chitatanga, R.; Chuki, P.; Gandra, S.; Getahun, H.; Harbarth, S.; et al. The WHO essential medicines list AWaRe book: From a list to a quality improvement system. Clin. Microbiol. Infect. 2022, 28, 1533–1535. [Google Scholar] [CrossRef] [PubMed]
  61. Deville, J.G.; Song, E.; Ouellette, C.P. COVID-19: Clinical Manifestations and Diagnosis in Children. 2023. Available online: https://www.uptodate.com/contents/covid-19-clinical-manifestations-and-diagnosis-in-children# (accessed on 8 January 2023).
  62. Dona, D.; Montagnani, C.; Di Chiara, C.; Venturini, E.; Galli, L.; Lo Vecchio, A.; Denina, M.; Olivini, N.; Bruzzese, E.; Campana, A.; et al. COVID-19 in Infants Less than 3 Months: Severe or Not Severe Disease? Viruses 2022, 14, 2256. [Google Scholar] [CrossRef]
  63. Mahmoudi, S.; Mehdizadeh, M.; Badv, R.S.; Navaeian, A.; Pourakbari, B.; Rostamyan, M.; Ekbatani, M.S.; Eshaghi, H.; Abdolsalehi, M.R.; Alimadadi, H.; et al. The Coronavirus Disease 2019 (COVID-19) in Children: A Study in an Iranian Children’s Referral Hospital. Infect. Drug Resist. 2020, 13, 2649–2655. [Google Scholar] [CrossRef]
  64. Preston, L.E.; Chevinsky, J.R.; Kompaniyets, L.; Lavery, A.M.; Kimball, A.; Boehmer, T.K.; Goodman, A.B. Characteristics and Disease Severity of US Children and Adolescents Diagnosed With COVID-19. JAMA Netw. Open 2021, 4, e215298. [Google Scholar] [CrossRef]
  65. Shaiba, L.A.; Altirkawi, K.; Hadid, A.; Alsubaie, S.; Alharbi, O.; Alkhalaf, H.; Alharbi, M.; Alruqaie, N.; Alzomor, O.; Almughaileth, F.; et al. COVID-19 Disease in Infants Less Than 90 Days: Case Series. Front. Pediatr. 2021, 9, 674899. [Google Scholar] [CrossRef]
  66. Butt, A.A.; Dargham, S.R.; Loka, S.; Shaik, R.M.; Chemaitelly, H.; Tang, P.; Hasan, M.R.; Coyle, P.V.; Yassine, H.M.; Al-Khatib, H.A.; et al. Coronavirus Disease 2019 Disease Severity in Children Infected with the Omicron Variant. Clin. Infect. Dis. 2022, 75, e361–e367. [Google Scholar] [CrossRef]
  67. Guner Ozenen, G.; Sahbudak Bal, Z.; Umit, Z.; Bilen, N.M.; Yildirim Arslan, S.; Yurtseven, A.; Saz, E.U.; Burcu, B.; Sertoz, R.; Kurugol, Z.; et al. Demographic, clinical, and laboratory features of COVID-19 in children: The role of mean platelet volume in predicting hospitalization and severity. J. Med. Virol. 2021, 93, 3227–3237. [Google Scholar] [CrossRef]
  68. Kitano, T.; Kitano, M.; Krueger, C.; Jamal, H.; Al Rawahi, H.; Lee-Krueger, R.; Sun, R.D.; Isabel, S.; García-Ascaso, M.T.; Hibino, H.; et al. The differential impact of pediatric COVID-19 between high-income countries and low- and middle-income countries: A systematic review of fatality and ICU admission in children worldwide. PLoS ONE 2021, 16, e0246326. [Google Scholar] [CrossRef] [PubMed]
  69. Ungar, S.P.; Solomon, S.; Stachel, A.; Shust, G.F.; Clouser, K.N.; Bhavsar, S.M.; Lighter, J. Hospital and ICU Admission Risk Associated with Comorbidities Among Children with COVID-19 Ancestral Strains. Clin. Pediatr. 2023, 00099228221150605. [Google Scholar] [CrossRef]
  70. Ward, J.L.; Harwood, R.; Smith, C.; Kenny, S.; Clark, M.; Davis, P.J.; Draper, E.S.; Hargreaves, D.; Ladhani, S.; Linney, M.; et al. Risk factors for PICU admission and death among children and young people hospitalized with COVID-19 and PIMS-TS in England during the first pandemic year. Nat. Med. 2021, 28, 193–200. [Google Scholar] [CrossRef]
  71. Aguilera-Alonso, D.; Epalza, C.; Sanz-Santaeufemia, F.J.; Grasa, C.; Villanueva-Medina, S.; Pérez, S.M.; Hernández, E.C.; Urretavizcaya-Martínez, M.; Pino, R.; Gómez, M.N.; et al. Antibiotic Prescribing in Children Hospitalized With COVID-19 and Multisystem Inflammatory Syndrome in Spain: Prevalence, Trends, and Associated Factors. J. Pediatr. Infect. Dis. Soc. 2022, 11, 225–228. [Google Scholar] [CrossRef]
  72. Du, W.; Yu, J.; Wang, H.; Zhang, X.; Zhang, S.; Li, Q.; Zhang, Z. Clinical characteristics of COVID-19 in children compared with adults in Shandong Province, China. Infection 2020, 48, 445–452. [Google Scholar] [CrossRef]
  73. Taheri, L.; Gheiasi, S.F.; Taher, M.; Basirinezhad, M.H.; Shaikh, Z.A.; Dehghan Nayeri, N. Clinical Features of COVID-19 in Newborns, Infants, and Children: A Systematic Review and Meta-analysis. Compr. Child Adolesc. Nurs. 2021, 45, 137–155. [Google Scholar] [CrossRef]
  74. García, H.; Allende-López, A.; Morales-Ruíz, P.; Miranda-Novales, G.; Villasis-Keever, M.; COVID-19 in Neonates with Positive RT-PCR Test. Systematic Review. Arch. Med. Res. 2022, 53, 252–262. [Google Scholar] [CrossRef] [PubMed]
  75. Spoulou, V.; Noni, M.; Koukou, D.; Kossyvakis, A.; Michos, A. Clinical characteristics of COVID-19 in neonates and young infants. Eur. J. Pediatr. 2021, 180, 3041–3045. [Google Scholar] [CrossRef] [PubMed]
  76. de Jaegere, T.M.H.; Krdzalic, J.; Fasen, B.; Kwee, R.M. Radiological Society of North America Chest CT Classification System for Reporting COVID-19 Pneumonia: Interobserver Variability and Correlation with Reverse-Transcription Polymerase Chain Reaction. Radiol. Cardiothorac. Imaging 2020, 2, e200213. [Google Scholar] [CrossRef] [PubMed]
  77. Yock-Corrales, A.; Lenzi, J.; Ulloa-Gutiérrez, R.; Gómez-Vargas, J.; Antúnez-Montes, O.Y.; Aida, J.A.R.; del Aguila, O.; Arteaga-Menchaca, E.; Campos, F.; Uribe, F.; et al. High rates of antibiotic prescriptions in children with COVID-19 or multisystem inflammatory syndrome: A multinational experience in 990 cases from Latin America. Acta Paediatr. 2021, 110, 1902–1910. [Google Scholar] [CrossRef]
  78. Saleem, Z.; Hassali, M.A.; Hashmi, F.K. Pakistan’s national action plan for antimicrobial resistance: Translating ideas into reality. Lancet Infect. Dis. 2018, 18, 1066–1067. [Google Scholar] [CrossRef]
  79. Saleem, Z.; Godman, B.; Azhar, F.; Kalungia, A.C.; Fadare, J.; Opanga, S.; Markovic-Pekovic, V.; Hoxha, I.; Saeed, A.; Al-Gethamy, M.; et al. Progress on the national action plan of Pakistan on antimicrobial resistance (AMR): A narrative review and the implications. Expert Rev. Anti-Infect. Ther. 2021, 20, 71–93. [Google Scholar] [CrossRef]
  80. Siachalinga, L.; Mufwambi, W.; Lee, L.-H. Impact of antimicrobial stewardship interventions to improve antibiotic prescribing for hospital inpatients in Africa: A systematic review and meta-analysis. J. Hosp. Infect. 2022, 129, 124–143. [Google Scholar] [CrossRef]
  81. Akpan, M.R.; Isemin, N.U.; Udoh, A.E.; Ashiru-Oredope, D. Implementation of antimicrobial stewardship programmes in African countries: A systematic literature review. J. Glob. Antimicrob. Resist. 2020, 22, 317–324. [Google Scholar] [CrossRef]
  82. Cox, J.A.; Vlieghe, E.; Mendelson, M.; Wertheim, H.; Ndegwa, L.; Villegas, M.V.; Gould, I.; Hara, G.L. Antibiotic stewardship in low- and middle-income countries: The same but different? Clin. Microbiol. Infect. 2017, 23, 812–818. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  83. Saleem, Z.; Godman, B.; Cook, A.; Khan, M.A.; Campbell, S.M.; Seaton, R.A.; Siachalinga, L.; Haseeb, A.; Amir, A.; Kurdi, A.; et al. Ongoing Efforts to Improve Antimicrobial Utilization in Hospitals among African Countries and Implications for the Future. Antibiotics 2022, 11, 1824. [Google Scholar] [CrossRef]
  84. WHO. The WHO AWaRe (Access, Watch, Reserve) Antibiotic Book. 2022. Available online: https://www.who.int/publications/i/item/9789240062382 (accessed on 1 February 2023).
  85. Hussain, M.; Al Mamun, M.A. COVID-19 in children in Bangladesh: Situation analysis. Asia Pac. J. Paediatr. Child Health 2020, 3, 59–65. [Google Scholar]
  86. Saleem, Z.; Haseeb, A.; Godman, B.; Batool, N.; Altaf, U.; Ahsan, U.; Khan, F.U.; Mustafa, Z.U.; Nadeem, M.U.; Farrukh, M.J.; et al. Point Prevalence Survey of Antimicrobial Use during the COVID-19 Pandemic among Different Hospitals in Pakistan: Findings and Implications. Antibiotics 2022, 12, 70. [Google Scholar] [CrossRef]
  87. Mustafa, Z.U.; Salman, M.; Yasir, M.; Godman, B.; Majeed, H.A.; Kanwal, M.; Iqbal, M.; Riaz, M.B.; Hayat, K.; Hasan, S.S. Antibiotic consumption among hospitalized neonates and children in Punjab province, Pakistan. Expert Rev. Anti-Infect. Ther. 2021, 20, 931–939. [Google Scholar] [CrossRef]
  88. Mustafa, Z.U.; Majeed, H.K.; Latif, S.; Salman, M.; Hayat, K.; Mallhi, T.H.; Khan, Y.H.; Khan, A.H.; Abubakar, U.; Sultana, K.; et al. Adherence to Infection Prevention and Control Measures Among Health-Care Workers Serving in COVID-19 Treatment Centers in Punjab, Pakistan. Disaster Med. Public Health Prep. 2023, 17, e298. [Google Scholar] [CrossRef] [PubMed]
  89. Kamran, S.H.; Mustafa, Z.U.; Rao, A.Z.; Hasan, S.S.; Zahoor, F.; Sarwar, M.U.; Khan, S.; Butt, S.; Rameez, M.; Abbas, M.A.; et al. SARS-CoV-2 infection pattern, transmission and treatment: Multi-center study in low to middle-income districts hospitals in Punjab, Pakistan. Pak. J. Pharm. Sci. 2021, 34, 1135–1142. [Google Scholar]
  90. Mustafa, Z.U.; Kow, C.S.; Salman, M.; Kanwal, M.; Riaz, M.B.; Parveen, S.; Hasan, S.S. Pattern of medication utilization in hospitalized patients with COVID-19 in three District Headquarters Hospitals in the Punjab province of Pakistan. Explor. Res. Clin. Soc. Pharm. 2021, 5, 100101. [Google Scholar] [CrossRef]
  91. Government of Pakistan. Ministry Of National Health Services, Regulations and Coordination. In Clinical Management Guidelines for COVID-19 Infections; 2020. Available online: https://nhsrc.gov.pk/SiteImage/Misc/files/20200704%20Clinical%20Management%20Guidelines%20for%20COVID-19%20infections_1203.pdf (accessed on 3 January 2023).
  92. Godman, B.; Haque, M.; Islam, S.; Iqbal, S.; Urmi, U.L.; Kamal, Z.M.; Shuvo, S.A.; Rahman, A.; Kamal, M.; Haque, M.; et al. Rapid Assessment of Price Instability and Paucity of Medicines and Protection for COVID-19 Across Asia: Findings and Public Health Implications for the Future. Front. Public Health 2020, 8, 585832. [Google Scholar] [CrossRef]
  93. WHO. Anatomical Therapeutic Chemical (ATC) Classification. 2021. Available online: https://www.who.int/tools/atc-ddd-toolkit/atc-classification (accessed on 5 January 2023).
  94. Hsia, Y.; Lee, B.R.; Versporten, A.; Yang, Y.; Bielicki, J.; Jackson, C.; Newland, J.; Goossens, H.; Magrini, N.; Sharland, M.; et al. Use of the WHO Access, Watch, and Reserve classification to define patterns of hospital antibiotic use (AWaRe): An analysis of paediatric survey data from 56 countries. Lancet Glob. Health 2019, 7, e861–e871. [Google Scholar] [CrossRef] [Green Version]
  95. Sharland, M.; Pulcini, C.; Harbarth, S.; Zeng, M.; Gandra, S.; Mathur, S.; Magrini, N. Classifying antibiotics in the WHO Essential Medicines List for optimal use—Be AWaRe. Lancet Infect. Dis. 2018, 18, 18–20. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  96. Klein, E.Y.; Milkowska-Shibata, M.; Tseng, K.K.; Sharland, M.; Gandra, S.; Pulcini, C.; Laxminarayan, R. Assessment of WHO antibiotic consumption and access targets in 76 countries, 2000–15: An analysis of pharmaceutical sales data. Lancet Infect. Dis. 2020, 21, 107–115. [Google Scholar] [CrossRef] [PubMed]
  97. Godman, B.; Momanyi, L.; Opanga, S.; Nyamu, D.; Oluka, M.; Kurdi, A. Antibiotic prescribing patterns at a leading referral hospital in Kenya: A point prevalence survey. J. Res. Pharm. Pract. 2019, 8, 149–154. [Google Scholar] [CrossRef]
  98. Okoth, C.; Opanga, S.; Okalebo, F.; Oluka, M.; Kurdi, A.; Godman, B. Point prevalence survey of antibiotic use and resistance at a referral hospital in Kenya: Findings and implications. Hosp. Pract. 2018, 46, 128–136. [Google Scholar] [CrossRef] [Green Version]
  99. Dlamini, N.N.; Meyer, J.C.; Kruger, D.; Kurdi, A.; Godman, B.; Schellack, N. Feasibility of using point prevalence surveys to assess antimicrobial utilisation in public hospitals in South Africa: A pilot study and implications. Hosp. Pract. 2019, 47, 88–95. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  100. Skosana, P.; Schellack, N.; Godman, B.; Kurdi, A.; Bennie, M.; Kruger, D.; Meyer, J. A point prevalence survey of antimicrobial utilisation patterns and quality indices amongst hospitals in South Africa; findings and implications. Expert Rev. Anti-Infect. Ther. 2021, 19, 1353–1366. [Google Scholar] [CrossRef]
  101. Saleem, Z.; Hassali, M.A.; Versporten, A.; Godman, B.; Hashmi, F.K.; Goossens, H.; Saleem, F. A multicenter point prevalence survey of antibiotic use in Punjab, Pakistan: Findings and implications. Expert Rev. Anti-Infect. Ther. 2019, 17, 285–293. [Google Scholar] [CrossRef] [Green Version]
  102. Kurdi, A.; Hasan, A.J.; Baker, K.I.; Seaton, R.A.; Ramzi, Z.S.; Sneddon, J.; Godman, B. A multicentre point prevalence survey of hospital antibiotic prescribing and quality indices in the Kurdistan regional government of Northern Iraq: The need for urgent action. Expert Rev. Anti-Infect. Ther. 2020, 19, 805–814. [Google Scholar] [CrossRef]
Antibiotics 12 00646 g001 550
Figure 1. Flow chart of identification of COVID patients aged ≤ 12 for inclusion in the study.
Figure 1. Flow chart of identification of COVID patients aged ≤ 12 for inclusion in the study.
Antibiotics 12 00646 g001
Antibiotics 12 00646 g002 550
Figure 2. Details of medication prescribed to the study population. NB: * Intravenous fluids and/or inhalation fluids.
Figure 2. Details of medication prescribed to the study population. NB: * Intravenous fluids and/or inhalation fluids.
Antibiotics 12 00646 g002
Antibiotics 12 00646 g003 550
Figure 3. Antibiotic usage classified according to WHO AWaRe Classification. NB: Please refer to the methodology for the definitions of the AWaRe groupings.
Figure 3. Antibiotic usage classified according to WHO AWaRe Classification. NB: Please refer to the methodology for the definitions of the AWaRe groupings.
Antibiotics 12 00646 g003
Antibiotics 12 00646 g004 550
Figure 4. Findings of the blood culture tests (N = 28).
Figure 4. Findings of the blood culture tests (N = 28).
Antibiotics 12 00646 g004
Table
Table 1. Demographic and clinical characteristics of the sample.
Table 1. Demographic and clinical characteristics of the sample.
VariablesN (%)
Number of patients per hospital
H1225 (52.0)
H257 (13.2)
H350 (11.5)
H4101 (23.3)
Age
Neonate (1–28 days)17 (3.9)
Infant (1–12 months)75 (17.3)
Toddler (1–5 years)146 (33.7)
Child (5–12 years)195 (45.0)
Gender
Male275 (63.5)
Female158 (36.5)
Residence
Rural125 (28.9)
Urban308 (71.1)
Comorbidity (including low birth weight, preterm and anemia)
Yes44 (10.2)
No389 (89.8)
COVID status
Positive372 (85.9)
Suspected61 (14.1)
Severity of COVID-19 (N = 372)
Asymptomatic18 (4.8)
Mild80 (21.5)
Moderate100 (26.9)
Severe142 (38.2)
Critical32 (8.6)
ICU admission
Yes162 (37.4)
No271 (62.6)
Invasive mechanical ventilation
Yes12 (2.8)
No421 (97.2)
Signs and symptoms402 (92.8)
Tachypnea269 (62.1)
Decreased level of consciousness117 (27.0)
Cough286 (66.1)
Fever311 (71.8)
Sore throat216 (30.5)
Headache/body aches132 (30.5)
Lethargy160 (37.0)
Nausea/vomiting191 (44.1)
Diarrhea76 (11.3)
Others49 (11.3)
Lab and other findings
Positive imaging findings351 (81.1)
Elevated WBCs282 (65.1)
Elevated CRP164 (37.9)
Elevated D-dimer93 (21.5)
Elevated ferritin55 (12.7)
Bacterial culture testing28 (6.5)
Length of stay
≤7 days112 (25.9)
8–14 days227 (52.4)
15–21 days74 (17.1)
>21 days20 (4.6)
NB: ICU—Intensive Care Unit.
Table
Table 2. Details of antibiotics used in the study population.
Table 2. Details of antibiotics used in the study population.
VariablesN (%)
Neonates and children prescribed antibiotics
Yes370 (85.5)
No63 (14.5)
Total number of antibiotics prescribed to all the children prescribed antibiotics (N = 370)736
Average antibiotics prescribed per patient (Mean ± SD)1.70 ± 0.98
Number of antibiotics prescribed per patients (N = 370)
One92 (24.9)
Two201 (54.3)
Three or more77 (20.8)
Route of antibiotic therapy (N = 736)
Intravenous556 (75.5)
Oral180 (24.5)
Duration of antibiotic therapy
≤5 days423 (57.5)
6–10 days290 (39.4)
>10 days23 (3.1)
Table
Table 3. Details of prescribed antibiotics according to Anatomical Therapeutic Chemical (ATC) and AWaRe Classification.
Table 3. Details of prescribed antibiotics according to Anatomical Therapeutic Chemical (ATC) and AWaRe Classification.
ATC ClassSubclassName of the Antibiotic and ATC ClassAWaRe ClassN
Beta-lactam antibacterials, penicillins (J01C)Penicillins with extended spectrum (J01CA)Amoxicillin
(J01CA04)		Access2
Ampicillin
(J01CA01)		Access11
Co-amoxiclav
(J01CR02)		Access40
Combinations of penicillins, including beta-lactamase inhibitors (J01CR)Piperacillin + Tazobactam
(J01CR05)		Watch32
Other beta-lactam antibacterials (J01D)Carbapenems (J01DH)Meropenem
(J01DH02)		Watch74
Third-generation cephalosporins (J01DD)Ceftriaxone
(J01DD04)		Watch173
Ceftazidime
(J01DD02)		Watch19
Cephoperazone
(J01DD12)		Watch12
Cefotaxime
(J01DD01)		Watch16
Cefixime
(J01DD08)		Watch2
Fourth-generation cephalosporins (J01DE)Cefepime
(J01DE01)		Watch35
Macrolides, lincosamides and streptogramins (J01F)Macrolides (J01FA)Azithromycin (J01FA10)Watch183
Clarithromycin
(J01FA09)		Watch5
Quinolone antibacterials (J01M)Fluoroquinolones (J01MA)Ciprofloxacin
(J01MA02)		Watch11
Levofloxacin
(J01MA12)		Watch3
Moxifloxacin
(J01MA14)		Watch2
Aminoglycoside antibacterials (J01G)Other aminoglycosides (J01GB)Amikacin
(J01GB06)		Access60
Other antibacterials (J01X)Glycopeptide antibacterials (J01XA)Vancomycin
(J01XA01)		Watch25
Imidazole derivatives (J01XD)Metronidazole
(J01XD01)		Access10
Other antibacterials (J01XX)Linezolid
(J01XX08)		Reserve21
NB: Details of the AWaRe classification and its importance are in methodology.
Table
Table 4. Comparison of antibiotic usage among selected variables.
Table 4. Comparison of antibiotic usage among selected variables.
VariablesNo. of Antibioticsp-Value
Hospitals
H11.81 ± 0.950.001
H22.11 ± 0.77
H31.44 ± 1.03
H41.35 ± 1.00
Age
Neonate (1–28 days)1.53 ± 0.800.483
Infant (1–12 months)1.69 ± 1.01
Toddler (1–5 years)1.79 ± 1.00
Child (5–12 years)1.65 ± 0.97
Gender
Male1.70 ± 1.010.954
Female1.70 ± 0.94
Residence
Rural1.71 ± 0.970.869
Urban1.69 ± 0.98
Comorbidity
Yes1.84 ± 1.120.314
No1.68 ± 0.96
COVID status
Positive1.76 ± 0.980.002
Suspected1.34 ± 0.89
Severity of COVID (N = 372)
Asymptomatic0.44 ± 0.78<0.001
Mild1.05 ± 1.11
Moderate1.68 ± 0.68
Severe2.16 ± 0.65
Critical2.72 ± 0.81
ICU admission
Yes2.22 ± 0.71<0.001
No1.39 ± 0.99
Invasive mechanical ventilation
Yes2.67 ± 0.65<0.001
No1.67 ± 0.97
X-ray abnormalities
Yes1.83 ± 1.88<0.001
No1.12 ± 1.17
Elevated WBCs
Yes1.95 ± 0.86<0.001
No1.23 ± 1.02
Elevated CRP
Yes2.19 ± 0.74<0.001
No1.41 ± 0.99
Elevated D-dimer
Yes2.16 ± 0.74<0.001
No1.57 ± 1.00
Elevated ferritin
Yes2.22 ± 0.81<0.001
No1.62 ± 0.98
Bacterial culture testing
Yes1.96 ± 0.840.098
No1.68 ± 0.99
Length of stay
≤7 days1.04 ± 1.03<0.001
8–14 days1.73 ± 0.81
15–21 days2.28 ± 0.73
>21 days2.95 ± 0.39
NB: Bold = statistically significant.
Table
Table 5. Post hoc analysis of antibiotic use among hospital and COVID-19 severity categories.
Table 5. Post hoc analysis of antibiotic use among hospital and COVID-19 severity categories.
ComparisonMean DifferenceStandard Errorp-Value
Hospital
H1 vs. H2−0.290.120.078
H1 vs. H30.370.160.098
H1 vs. H40.470.120.001
H2 vs. H30.670.180.002
H2 vs. H40.760.14<0.001
H3 vs. H40.090.180.952
COVID-19 severity
Asymptomatic vs. mild−0.610.220.072
Asymptomatic vs. moderate−1.240.20<0.001
Asymptomatic vs. severe−1.720.19<0.001
Asymptomatic vs. critical−2.270.23<0.001
Mild vs. moderate−0.630.14<0.001
Mild vs. severe−1.110.14<0.001
Mild vs. critical−1.670.19<0.001
Moderate vs. severe−0.480.09<0.001
Moderate vs. critical−1.040.16<0.001
Severe vs. critical−0.560.150.007
Length of hospital stay (days)
≤7 vs. 8–14−0.690.11<0.001
≤7 vs. 15–21−1.250.13<0.001
≤7 vs. >21−1.910.13<0.001
8–14 vs. 15–21−0.560.10<0.001
8–14 vs. >21−1.220.10<0.001
15–21 vs. >21−0.670.12<0.001
NB: Bold = statistically significant.
Table
Table 6. Factors associated with antibiotic use in children with COVID-19.
Table 6. Factors associated with antibiotic use in children with COVID-19.
Coefficients a,b
ModelUnstandardized CoefficientsStandardized CoefficientsTSig.95% CI for B
BSEBetaLower BoundUpper Bound
(Constant)0.0100.149 0.0680.946−0.2820.302
COVID-19 severity0.4040.0440.4279.226<0.0010.3180.490
Length of hospital stay0.3700.0580.2936.325<0.0010.2550.485
Hospital−0.1570.030−0.204−5.185<0.001−0.217−0.098
a Number of prescribed antibiotics. b Selecting only cases for which COVID-19 status = Positive.
Table
Table 7. Findings of culture and sensitivity testing.
Table 7. Findings of culture and sensitivity testing.
PathogenNSensitivity Results
S. pneumonia3Linezolid, levofloxacin, vancomycin
P. aeruginosa4Ceftriaxone, carbapenems
P. aeruginosa2Ceftriaxone, carbapenems, aminoglycosides
P. aeruginosa3Meropenem
K. pneumoniae2Pipericillin, ceftazidime, meropenem
E. coli1Pipericillin, metronidazole
S. aureus1Levofloxacin, imipenem
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

Share and Cite

MDPI and ACS Style

Mustafa, Z.U.; Khan, A.H.; Harun, S.N.; Salman, M.; Godman, B. Antibiotic Overprescribing among Neonates and Children Hospitalized with COVID-19 in Pakistan and the Implications. Antibiotics 2023, 12, 646. https://doi.org/10.3390/antibiotics12040646

AMA Style

Mustafa ZU, Khan AH, Harun SN, Salman M, Godman B. Antibiotic Overprescribing among Neonates and Children Hospitalized with COVID-19 in Pakistan and the Implications. Antibiotics. 2023; 12(4):646. https://doi.org/10.3390/antibiotics12040646

Chicago/Turabian Style

Mustafa, Zia UI, Amer Hayat Khan, Sabariah Noor Harun, Muhammad Salman, and Brian Godman. 2023. "Antibiotic Overprescribing among Neonates and Children Hospitalized with COVID-19 in Pakistan and the Implications" Antibiotics 12, no. 4: 646. https://doi.org/10.3390/antibiotics12040646

APA Style

Mustafa, Z. U., Khan, A. H., Harun, S. N., Salman, M., & Godman, B. (2023). Antibiotic Overprescribing among Neonates and Children Hospitalized with COVID-19 in Pakistan and the Implications. Antibiotics, 12(4), 646. https://doi.org/10.3390/antibiotics12040646

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop