Background:

Infections with resistant organisms have higher morbidity and mortality, are costlier to treat,
result in longer hospital stays and place a greater burden on health systems than infections
caused by susceptible organisms. Surveillance across all countries is needed to monitor and
respond to this emerging threat.
Method
We compared the trend of antimicrobial resistants (AMRs) in clinical isolates, divided by year
and bacteria spp., of samples obtained from nosocomial and community patients. Patient records
were collected, including age, sex, site of infection, isolated organisms, and drug susceptibility
patterns. A retrospective record review of data collected from the microbiology department at a
private laboratory between January 2012 and December 2017 was done. The outcome of interest
was the antibiotic susceptibility of bacterial isolates. Microsoft Excel 2016 was used to plot
trends from 2012 to 2017 and Epi Info™7 was used for statistical analysis. Here, we present a
systematic review and meta-analysis of 749 point prevalence surveys reporting antibiotic-
resistant bacteria from aquatic food animals in Asia, extracted from 343 articles published in
2000–2019. To explore the trends and correlation between antibiotics consumption and
antimicrobial resistance in children in a specialist hospital from 2016–2021 in China. This
retrospective study investigated data on the consumption of antibiotics and antimicrobial
resistance in children. The trends in antibiotics consumption and antimicrobial resistance rates
were analyzed by linear regression, while Spearman correlation analysis was employed to
evaluate their correlations.
Results
From 2019 to 2022, a total of 113,635 bacterial isolates were tested, of which 11,901 resulted in
antimicrobial resistants. An increase in the prevalence of several antibiotics resistant bacteria
was observed. Specifically, the percentage of CPO cases increased from 2.62% to 4.56%, the
percentage of MRSA increased from 1.84% to 2.81%, and the percentage of VRE increased from
0.58% to 2.21%. AMRs trend resulted in increases in CPO and MRSA for both community and
nosocomial. The proportion of important multidrugresistant pathogens remained stable over the
years. While the analysis showed diverse AMR profiles for different bacterial species. Over the
five years, generally decreased resistance rates were observed from the majority of the tested
species. For example, resistance to ceftriaxone decreased in Escherichia coli and Klebsiella
pneumoniae, while resistance to imipenem and meropenem decreased in Pseudomonas
aeruginosa. Moreover, resistance to methicillin, gentamicin, fosfomycin, and clindamycin also
decreased in clinical Staphylococcus aureus isolates. On the other hand, resistance levels of
Acinetobacter baumannii remained stable. The implementation of AMR surveillance in
Zimbabwe is limited. The increasing resistance rates indicate that Zimbabwe is affected by
AMR. This study was done to determine the magnitude of AMR in Harare and determine the
trends of AMR to first-line and to last-resort antibiotics and make recommendations to mitigate
the problem. Resistance was highest to ampicillin followed by penicillin, both ranging between
70 and 100% over the six years. Statistically significant increases in resistance to commonly
used antibiotics were observed in amoxicillin-resistant E. coli and Streptococcus pneumonia and
third generation cephalosporinresistant E. coli. There was an increase in resistance to last-line
antibiotics i.e., fluoroquinolone-resistant Salmonella spp. and carbapenem-resistant
Pseudomonas aeruginosa and Acinetobacter baumannii. However, methicillin-resistant S. aureus
showed a decreasing trend. A significant upward trend was detected in the annual resistance
rates of Enterococcus faecium to ciprofloxacin, Streptococcus pneumonia to ceftriaxone,
Acinetobacter baumannii to carbapenems, Enterobacter cloacae to carbapenems, Pseudomonas
aeruginosa to ceftazidime, and Escherichia coli to cefepime, while the annual resistance rates of
Escherichia coli to carbapenems had a significant downward trend (all P<0.05).
Conclusions: There is a high burden of drug resistance to common antibiotics in Harare and an
emergence of resistance to last-line antibiotics.
Introduction
AMR
Since the 1950s, this phenomenon has increased and is still increasing in recent years, affecting
countries, and increasing morbidity and mortality. AMR is a rising global epidemic that is
typically attributed to“selective pressure” brought on by excessive, or inappropriate use of
antibiotics in people and animals [3]. The WHO shared a list of “priority status” pathogens,
defined as ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae,
Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) pathogens to
focus and guide the development of new antibiotics [7,8]. In 2019, the WHO estimated 133,000
deaths attributable to AMR in Europe [24], implementing the surveillance against antimicrobial
resistance with the National Action Plans (NAP) against Antimicrobial Resistance.
Antimicrobial resistance (AMR) is a problem of increasing international concern (Trends 5).
AMR is the ability of microbes to withstand the effects of the antimicrobial therapies that were
previously effective in treating infections caused by such microbes (Trends 5). However, the
prevalence of drug-resistant pathogens varies greatly across regions (Trends 5). In high-income
countries, high levels of per capita antimicrobial consumption since the 1950s have driven the
selection of resistant bacteria,4 and recent initiatives to curb antimicrobial use have had limited
impact on consumption.5,6 (Trends 5) In middle-income countries, which are rapidly converging
to consumption levels found in high-income countries,7 poor sanitation, a continued high
background burden of bacterial infections and the increasing use of antibiotics have facilitated
the rapid growth and spread of AMR.8,9 (Trends 5). Antimicrobial use exerts selective pressures
driving antimicrobial resistance. In terrestrial animals, a growing body of evidence has linked
AMR with productivity loss and resistant infections carrying harmful consequences to animal
and human health6–9 (Trends 6) Rising AMR rates are expected to disproportionately affect
low-income and middle-income countries, jeopardizing development gains in vulnerable
communities, widening economic inequality, and contributing to a rise in extreme poverty by
203022. (Trends 6) The widespread emergence of antibacterial resistance has become one of
the major public health concerns for humankind due to unresponsiveness to treatment, which
results in persistent illness and increased risk of death.1 (Trends 8) Specifically, multidrug-
resistant organisms (MDROs) damage not only the infected patients but also other individuals.
On the other hand, antibacterial resistance has brought a tremendous economic burden (Trends
8). Since the selection pressure contributed by continued high rates of antibiotic use has resulted
in sustained resistant strains, which force a shift to more expensive and more broad-spectrum
antibiotics and could be a vicious cycle.6 (Trends 8)
Methods
Different types of bacterial resistance can be distinguished, including natural and acquired
resistance, and each one can act with different mechanisms [4]. The resistance mechanisms
developed by bacteria are essentially four: specific modification of the target, leading to the loss
or decrease of the drug’s affinity for its target; enzymatic inactivation of the antibiotic with
modification of its active molecular part; decreased permeability, which results in a decrease in
the number or diameter of the porins in the outer membrane of the Gram-negatives, making it
impossible for the drug to enter or be absorbed at a lower rate; and expulsion of the antibiotic
from the cell through energy-dependent efflux pumps. Likewise, Vancomycin-resistant
enterococci (VREs) have emerged in recent years as epidemiologically relevant pathogens,
posing challenges both for case management for multidrug resistance and from a public health
perspective due to the potential risk of transferring vancomycin resistance genes to other Gram-
positive organisms.
Conclusion
The epidemiology of AMR globally appears to be very diverse, with significant differences
between countries; in some cases, large-scale epidemics have involved numerous hospitals in the
same region. In other contexts, the presence of these microorganisms has become endemic, while
there are countries where the phenomenon is emerging. However, the epidemiological situation
in other Italian regions is not known, nor is the level of diffusion of EPCs in non-hospital
settings. Our research could provide a preliminary overview. This study focuses on analyses of
CRE, CRAB, CRPA, VRE, and MRSA isolated in patients from hospital environments, trying to
compare the results to antibiotic resistance isolated in Italian patients from a non-nosocomial
ambient from 2019 to 2022. Antimicrobial resistance surveillance is essential in understanding
the antimicrobial susceptibility of pathogenic bacteria and their resistance trends to important
antimicrobial drugs. This is crucial for clinical anti-infection empirical management and precise
treatment [1, 2]. Our study highlights the current resistance trends in the above five target
species, demonstrates the importance of bacterial surveillance studies, and plays a critical role in
guiding empirical antimicrobial therapy in clinical practice. In summary, the resistance status and
trends of most antimicrobials against the five target species were relatively stable. In Africa,
AMR surveillance is limited, but the available data suggest up to 100% resistance to beta-lactam
antibiotics [3]. WHO reported resistance to last resort antibiotics like vancomycin, 3rd
generation cephalosporins, clindamycin and carbapenems by some organisms. Resistance to
these last line antibiotics led the WHO to advocate for research and development of more
antimicrobials for treatment of these priority organisms in 2017 [4]. Due to the varied
prescription behaviors, types of antibiotics, and status of pathogens resistance across countries or
regions, the current study could be useful to local physicians and policymakers when planning
effective intervention strategies to control the antibiotics use and reduce the antimicrobial
resistance in children.
Methods
This study retrospectively analyzed the data on antibiotics consumption and antimicrobial
resistance in a specialist children’s hospital from January 1, 2016 to December 31, 2021. A total
of 670 beds are available for children in this hospital, which has an average level of 27,664
inpatients and 885,332 outpatients in children each year during the study periods. This study was
approved by the clinical research ethics committee of the Maternal and Child Health Hospital of
Hubei Province (2020IEC029) and carried out in accordance with the Helsinki Declaration. The
need to obtain individual informed consent was waived because this study utilized existing data
collected from the hospital information system and did not pose any additional risks to the
patients. Before data analysis, patient records and information were anonymous and unidentified.
Inc/Exc
We only utilized the data of children, including the newborns, while the data regarding the
patients, >14-years-old, were excluded. All isolates with data of susceptibility results were
recruited, including the positive clinical specimens, such as blood, sputum, urine, cerebrospinal
fluid, bronchoalveolar lavage fluid, wound, and anaerobic specimens etc. between 2016 and
2021.
Data analysis
The resistance rate was defined as the percentage of resistant isolates among the tested isolates.
Isolates with intermediate susceptibility were not included in the analysis of resistance. It should
be pointed out that carbapenem- resistant bacteria in Enterobacteriaceae (CRE) were defined as
resistance to either of imipenem, meropenem, and ertapenem in the current study. Because
Pseudomonas aeruginosa (P. aeruginosa) and Acinetobacter baumannii (A. baumannii) exhibit
natural resistance to ertapenem, CR-AB and carbapenem-resistant Pseudomonas aeruginosa was
shown to have resistance to imipenem or meropenem.
Result
Bacterial incidence
The five most frequently isolated bacteria genera identified in our review—Vibrio, Aeromonas,
Streptococcus, Edwardsiella, and Escherichia (E.coli)— together accounted for 68.5% of
surveys. Vibrio spp. (n = 191) and Aeromonas spp. (n = 174) contributed nearly half of all
surveys. Figure 2 describs the AMRs trend during the study period divided by bacterial spp. An
increase in the positive rate has been registered for all the species except the Acinetobacter
baumanii. The sharp increase of E. faecium from 37% (55 out of 149) to 96% (602 out of 625)
can be clearly seen, as well as the increase of S. aureus from 33% (397 out of 1206) to 57% (966
out of 1698). Less evident from the graph, but equally consistent, is the increase observed for E.
coli (0.39% in 2019, 48 out of 12,163; 0.26% in 2020, 37 out of 14,178; 0.23% in 2021, 41 out
of 17,519; 1% in 2022, 60 out of 5276); for P. auroginosa from 5% (82 out of 1565) to 11% (296
out of 2654); and for E. faecalis (3% in 2019, 69 out of 2236; 4% in 2020, 99 out of 2598; 6% in
2021, 186 out of 2950; 5% in 2022, 159 out of 2989). A wavering trend, though growing, was
reported in Klebsiella pneumonieae (7% in 2019, 228 out of 3052; 11% in 2020, 421 out of
3681; 12% in 2021, 536 out of 4450; 5,31% in 2022, 974 out of 18,359), while in A. baumannii
isolates it was noted a moderate decrease from 67% (206 up to 308) to 53% (240 up to 454).
AMR A slight increase was observed for each resistance: from 2.62% (564 out of 17,092) in
2019 to 4.56% (1570 out of 26,734) in 2022 for CPO; from 1.84% (397 out of 2069) in 2019 to
2.81% (966 out of 4062) in 2022 for MRSA; from 0.58% (124 out of 2385) in 2019 to 2.21%
(761 out of 3615) in 2022for VRE. Amongst these foodborne pathogens, resistance was highest
to penicillins (60.4%), macrolides (34.2%), sulfonamides (32.9%), and tetracyclines (21.5%)
(Fig. 2). Although highly variable, mean resistance rates to the highest priority critically
important antimicrobials for human medicine28 were highest for macrolides (34.2%, 95% CI 33
to 35%) followed by third-generation and fourth-generation cephalosporins (17.5%, 95% CI 17
to 18%) and quinolones (16.2%, 95% CI 15 to 17%). Mean resistance to third-generation
cephalosporins in E.coli was 27.1% (95% CI 25 to 29%) across surveys. Resistance to
compounds in the reserve group of last-resort antimicrobials for human medicine29 varied by
pathogen: fosfomycin resistance in E.coli was 10.3% (95% CI 6 to 14%); polymyxin B
resistance in E.coli was 19.4% (95% CI 7 to 32%), in Vibrio spp. was 39.1% (95% CI 33 to
44%) and in Aeromonas spp. was 71.5% (95% CI 67 to 76%); and colistin resistance in E.coli
was 5.2% (95% CI 2 to 8%), in Vibrio spp. was 42.7% (95% CI 38 to 47%) and in Aeromonas
spp. was 51.5% (95% CI 46 to 57%). In Gramnegative bacteria across all surveys, the mean
colistin resistance was 41.3% (95% CI 39 to 44%).
E. coli
The resistance rates of E. coli to most antimicrobial agents decreased over the five years.
Specifically, the resistance rate of clinical E. coli isolates to ceftriaxone decreased from 57.5% to
50.8% (Fig. 3). The rate of imipenem- resistant isolates also decreased from 2% in 2018 to 1.5%
in 2022 (Fig. 3). Moreover, the resistance rates of E. coli to amikacin, piperacillin-tazobactam,
cefoperazone- sulbactam, meropenem, ciprofloxacin and levofloxacin decreased from 2.7% to
2.2%, from 5.3% to 4.3%, from 6.5% to 5.5%, from 2.1% to 1.6%, from 66% to 61.4% and from
58.9% to 53.2%, respectively. Additionally, the resistance rates of E. coli to cefepime, cefoxitin,
trimethoprim- sulfamethoxazole, and fosfomycin decreased from 27.3% to 25.1%, 13.5% to
9.7%, 56.2% to 51.8% and 5% to 4.4%, respectively. However, the resistance rates of colistin
and tigecycline fluctuated around 1.0% and 0.1%, respectively. Notably, the resistance rate of E.
coli to polymyxin B increased from 0.7% in 2018 to 1.0% in 2022 (Fig. 4 and Supplementary
Appendix Table 2).
Klebsiella pneumoniae
The resistance rate of K. pneumoniae isolates to ceftriaxone decreased from 46.0% to 42.7%
during the five-year period (Fig. 3). While K. pneumoniae isolates showed a relatively stable
resistance rates to imipenem, meropenem, amikacin, piperacillin-tazobactam, cefepime and
tigecycline (Figs. 3 and 5). While the resistance rates to cefoperazone-sulbactam, levofloxacin
and trimethoprim-sulfamethoxazole decreased from 33% to 30.9%, from 38% to 35.2% and from
38.2% to 32.9% respectively. However, a significant decrease in resistance was observed for
ceftazidime-avibactam and ciprofloxacin, from 9.8% to 4.8% and from 50.2% to 38.3%,
respectively. A significant increase in resistance was observed for polymyxin B, from 1.0% to
5.1%. The resistance rate of K. pneumoniae to cefoxitin increased from 25.2% to 27.9%. Colistin
and tigecycline resistance rates fluctuated around 2.5% and 4.0%, respectively. (Fig. 5 and
Supplementary Appendix Table 3).
Pseudomonas aeruginosa
P. aeruginosa resistance decreased for all antimicrobial agents, during the five-year period. The
rates of imipenem- and meropenem-resistant isolates decreased from 30.7% to 23.8% and from
25.8% to 19.2%, respectively, during the 5-year sampling period (Fig. 3 and Supplementary
Appendix Table 4). Resistance to ceftazidime- avibactam significantly decreased from 11.1% to
6.3%. Furthermore, the resistance rates to cefoperazone- sulbactam, piperacillin-tazobactam,
ceftazidime, ciprofloxacin and amikacin decreased from 17.1% to 15%, 16.7% to 13.5%, 19.3%
to 14.9%, 24.1% to 15.3%, and 6.2% to 3.8%, respectively. The resistance rates of colistin and
polymyxin B fluctuated around 1.5% and 0.5% respectively (Fig. 6 and Supplementary
Appendix Table 4).
Acinetobacter baumannii
During the five-year period, the resistance levels of A. baumannii isolates to imipenem and
meropenem remained relatively stable, decreasing from 78% to 75.6% and from 78.8% to
76.6%, respectively (Fig. 3). Resistance to cefoperazone-sulbactam, amikacin, and levofloxacin
increased from 52.5% to 58.7%, 57.8% to 59.2% and 61.5% to 63.1%, respectively. Resistance
to ampicillinsulbactam, piperacillin-tazobactam, ceftazidime, ciprofloxacin, and tigecycline
decreased from 72.6% to 68.7%, from 77.9% to 77.4%, from 77.7% to 74.5%, from 79.1% to
75.4% and from 5.1% to 2.5%, respectively. Colistin and polymyxin B resistance rates were
fluctuated around 1% and 0.5%, respectively (Fig. 7 and Supplementary Appendix Table 5).
Staphylococcus aureus
The prevalence of methicillin resistance in S. aureus isolates decreased from 34.4% in 2018 to
30.5% in 2022 (Fig. 3). Furthermore, a significant reduction in resistance rates was noted for
several antibiotics. For instance, the percentage of S. aureus isolates resistant to gentamicin,
fosfomycin and clindamycin decreased from 17%, 13%, and 38.9% to 8.4%, 3.4%, and 26.7%,
respectively. Similarly, resistance rates to rifampicin, ciprofloxacin, trimethoprim-
sulfamethoxazole, and erythromycin decreased from 4.9% to 1.7%, 19.5% to 12.7%, 14.7% to
10.4% and 64.3% to 52.7% respectively. Notably, no isolates were observed resistant to
vancomycin and linezolid. On the other hand, resistance rates to teicoplanin and tigecycline
remained relatively low, fluctuating around 0.1% and 0.3%, respectively (Fig. 8 and
Supplementary Appendix Table 6).
Trends of total antimicrobial resistance by common antibiotics
Ninety-five percent of all bacteria analysed were resistant to penicillin in 2012. The resistance
decreased to 71.4% in 2014 and by 2017 it had increased again to 98.7%. Resistance to
amoxicillin decreased from 85.9 to 75.8% between 2012 and 2016 before increasing to 87.7% in
2017. Total resistance to cotrimoxazole was constantly high, ranging between 58 and 62%
throughout the study period. Over the 6 years there was increasing resistance to ceftriaxone (R2
= 0.90; p < 0.01) and augmentin (R2 = 0.90; p < 0.01) (Fig. 1). Resistance to ciprofloxacin (not
shown in the figure) showed a slight increase from 28.9% in 2012 to 37.8% in 2017. Mean
foodborne pathogen resistance to carbapenems was low (2.8%, 95% CI 2 to 4%), with the
exception of Aeromonas spp. In Aeromonas spp. across all regions, carbapenem resistance
increased from 5.1% (95% CI 2 to 8%) before 2010 to 51.1% (95% CI 43 to 60%) after 2010 (p
< 0.0001). From 2016 to 2021, the annual trend showed a significant increase in the resistance
rates of E. faecium to ciprofloxacin, S. pneumoniae to ceftriaxone, A. baumannii to carbapenems,
E. cloacae to carbapenems, P. aeruginosa to ceftazidime, and E. coli to cefepime (all P < 0.05).
Most of the annual resistance rates were maintained stable, while only the annual resistance rate
of E. coli to carbapenems had a significant decreasing trend during the study period (P < 0.05).
The various resistance rates are shown in Supplementary Table 3. Although most of the
resistance rates were stable in this study, certain antimicrobial resistance rates should be under
intensive focus as follows: the annual resistance rates of E. coli to ampicillin were >50% in each
year, the resistance rates of E. cloacae to third-generation cephalosporins were all >10% and the
resistance rates of K. pneumonia to ampicillin sulbactam and aztreonam were all >20% etc.
Trends of resistance to common antibiotics by specific organisms
The trends of resistance to different antibiotics by specific organisms between 2012 and 2017 are
summarised in Table 2. Resistance to amoxicillin was highest among Gramnegative bacteria. E.
coli had high resistance to amoxicillin throughout the six years i.e., 96.2% in 2012 and decreased
to a minimum of 84.1% in 2015 then increased again to 97.4% in 2017 (R2 = 0.07; p = 0.59). S.
pneumoniae showed increasing resistance to amoxicillin (i.e., 4.35 to 56.3%) between 2012 and
2017: the trend was statistically significant with R2 = 0.83; p = 0.01. Resistance to augmentin by
E.coli was statistically significant i.e., 20.1% in 2012 to 40.2% in 2017 (R2 = 0.98; p < 0.01). S.
pneumoniae also showed increasing resistance to augmentin i.e., from 0% in 2012 to a 71.4%
peak in 2016 and then a decrease to 55.5% in 2017 (R2 = 0.87; p < 0.01). S. aureus showed
declining resistance to augmentin from 6.8 to 2.0% between 2012 and 2017 (R2 = 0.79; p = 0.02)
Fig. 2.
Trends of resistance to cephalosporins by specific organisms
Resistance to cephalosporins by E. coli increased from 20.3% in 2012 to 34.9% in 2017 (R2 =
0.89; p < 0.01) while a decrease was noted in Acinetobacter baumannii from 69.1 to 29.8% (R2
= 0.89; p < 0.01). Pseudomonas aeruginosa and Salmonella spp. both showed < 15% resistance
to 3rd generation cephalosporins (i.e., ceftazidime) between 2012 and 2017 (Fig. 3). N.
gonorrhoea and S. pneumoniae were susceptible to ceftriaxone with 0% resistance over the study
period (data not shown).
Discussion
In recent years, the speed of diffusion of AMR, responsible for both nosocomial and community-
based infections, has reached alarming levels [18]. We reviewed and mapped antimicrobial
resistance in aquatic food animals in Asia during a period of substantial industry growth. Our
findings indicate that between 2000 and 2018, antimicrobial resistance in bacteria from cultured
aquatic food animals was stable (33%) while the resistance from wild-caught aquatic food
animals decreased sharply (52% to 22%).
AMR trends
The significant overall increase in cases seen after 2020 could be due to the rise of access in the
hospital for SARS-CoV-2 infection recovery, which has led clinicians to prioritize and monitor
the surveillance in all the reports. The results obtained in this study emphasized the importance
of introducing active screening in hospitals and even in the community to identify vehicles of
AMR infection to prevent further transmission. Furthermore, active screening as part of a
broader infection prevention program can contain colonization rates. The percentages of
resistance to the main classes of antibiotics for the pathogens under surveillance, compared with
the national trend, remain high and/or rising over the years [25]. It cannot be excluded that the
increased incidence of antimicrobial resistance could be attributed to the excess use of
antimicrobial agents during the coronavirus disease 2019 (COVID-19) pandemic¸ which can be
seen in Figure 2 by the increase in resistance trend for 2021 and 2022 in E. coli (0.23% and 1%),
P. aeruginosa (9% and 11%), S. aureus (47% and 57%), and E. faecium (60% and 96%). Patients
with COVID-19 have been vulnerable to other secondary infections owing to multiple
comorbidities with severe COVID-19, prolonged hospitalization, and severe acute respiratory
syndrome coronavirus 2 (SARS-CoV- 2)-associated immune dysfunction. These hospital patients
have often acquired secondary bacterial infections [28], which can increase the odds of
developing AMR; however, even in community patients, resistance growth has been observed in
the last two years, especially for K. pneumoniae (2021: nosocomial, N, 56% vs. community, C
51%; 2022: N 51% vs. C 76%) and E. faecium (2021: N 45% vs. C 66%; 2022: N 83% vs. C
71%), possibly being more sensitive to other infections for the same excess in the use of
antibiotics. Moreover, the spread of SARS-CoV-2 among the population could have favorited
bacterial infections in the compromised immune systems patients by COVID-19 [29]. The
overuse of colistin to prevent the spread of Gram-negative bacteria in nosocomial patients
(CPO+ in 2020: 37%, 2021: 35%, 2022: 28%) [31]. Still, it is possible that this trend could be
inverted soon for the development of colistin resistance. Furthermore, self-antibiotic medication
and broad-spectrum antibiotics during the COVID-19 era, such as ampicillin, erythromycin, and
ciprofloxacin, were the risk factors for higher levels of Gram-positive bacteria resistance in
community patients [31]. The increasing resistance rates to last line antibiotics are very
worrisome and may lead to the spread of life-threatening infections especially in hospitals [14].
Antimicrobial resistance rates to augmentin and cephalosporins (though much lower than
amoxicillin and penicillin) were increasing significantly over time. The increases could be due to
a rise in their use as clinicians avoid the highly resisted amoxicillin and penicillin. From the
study findings, carbapenem resistance by Enterobacteriaceae was very low (i.e., < 1%)
throughout the 6 years in this study. The findings are consistent with Magwenzi et al. 2017 who
reported a low prevalence of carbapenem-resistant Enterobacteriaceae of 1% in Harare. An
increasing trend was seen in fluoroquinolone resistance by Salmonella spp. and Campylobacter
spp. According to the 2011 guidelines for the management of typhoid fever, ciprofloxacin is the
drug of choice over the traditional first-line drugs (i.e., chloramphenicol, ampicillin, amoxicillin
or cotrimoxazole) [28]. This empirical use of ciprofloxacin is a plausible cause of the increased
resistance. Mashe et al. 2016 reported a sharp increase in ciprofloxacin-resistant S. typhi. The
resistance rates were much lower in the current study probably because all Salmonella species
included and may have confounded the resistance rates of S. typhi [7]. They attributed it to
genetic mutations in the quinolone-resistant-determining regions and exchange of drug resistant
bacteria between animals and humans through acquisition of qnr genes. In this study, we
indicated the serious global health threat posed by third-generation cephalosporin-resistant K.
pneumoniae, fluoroquinolone-resistant E. coli, third-generation cephalosporin-resistant E. coli,
and MRSA compared to other combinations, as well as the significantly higher consumption
rates for broad-spectrum penicillins compared to the other classes of antibiotics on a global scale
(Trends 4). Additionally, our results suggest that the LMICs and HICs show completely opposite
trends in antibiotic resistance in bacterial pathogens and antibiotic consumption and that LMICs
generally present relatively higher resistance rates in common bacterial pathogens but lower
antibiotic consumption rates than HICs, indicating that LMICs might have relatively serious
problems of inappropriate antibiotic consumption (Trends 4).
The possibility that a proportion of the colistin resistance identified is acquired cannot be ruled
out, particularly through plasmid-mediated transfer amongst members of the Enterobacteriaceae
family48. (Trends 6) Such resistance may be attributable to the prolific use of colistin and other
polymyxins in the region, which is only recently evolving through national regulatory action, and
the possible recruitment of mcr-family mobile resistance determinants, their broad dissemination
through horizontal gene transfer, and the wide distribution potential of aquatic
environments14,48,49. (Trends 6) The high rates of resistance to multiple classes of critically
important antimicrobials in aquatic animal foodborne pathogens in our study raise urgent
concerns regarding both therapeutic efficacy of first-line antimicrobials and the further erosion of
last-resort therapeutic options for multi-drug resistant infections resulting in severe disease.
(Trends 6). According to CHINET, the integrated data of children and adults exhibited that the
rates of CRAB were >50% from 2010–2021.25–27 Although the rates of CRAB were all <50%
in this study period, the trend was significantly increasing and the resistance rate was up to
48.9% in 2021. Inconsistence with previous study that there was a significant decreased trend in
the resistance rates of E.cloacae to carbapenems,8 there was an obvious upward trend in our
study; however, our result was in agreement with the CHINET data. Our results showed that
increased consumption of the carbapenems was significantly associated with rising resistance
rates of A. baumannii to carbapenems, which was in accordance with a multicenter study with
data from 153 tertiary hospitals in China.13 Previous studies from high-income countries, such
as Korea and Saudi Arabia, also had similar results that increasing resistance of A. baumannii to
carbapenems was correlated to carbapenems exposure.28,29 Moreover, the resistance rate of E.
cloacae to carbapenems was positively correlated with carbapenems consumption in our study.
However, a contradictory result was detected in a tertiary hospital in China from 2012 to 2019.8
Under selective antibiotic pressure, P. aeruginosa clinical isolates have a remarkable capacity for
acquiring new resistance mechanisms,16 which included expressing metallo-enzymes that are
active against the most stable of the β- lactam classes, the carbapenems.31 Therefore, the
antibiotics of β-lactam classes and carbapenems could have a mutual effect on the resistance of
P. aeruginosa to these antibiotics. The current results demonstrated a significant positive
association between the consumption of carbapenems and the resistance of P. aeruginosa to
ceftazidime, which was consistent with a previous study in Germany.14 In addition, previous
studies from middle-income countries, such as China and Serbia, showed that the resistance rate
of P. aeruginosa to carbapenems had a positive correlation with the usage of antipseudomonal
third-generation cephalosporins and β-lactam, respectively.10,17 As mentioned above, these
could be attributed to the mutual effect on the resistance of P. aeruginosa to the antibiotics of β-
lactam classes and carbapenems. Furthermore, the upward resistance rate of P. aeruginosa to
ceftazidime was closely related to the increasing consumption of C/BLI combinations in this
study, which might imply this similar effect even when combining BLI.
Limitations
While we can explain some of these trends, there is a lot of genetic dynamism involved in
antimicrobial resistance. Also, some resistance genes are acquired from bacteria of a different
genus while other resistant strains come from other parts of the world through human migration.
The study had limitations since it was a retrospective study. It could not be ascertained whether
the infections were community acquired or nosocomial or whether resistance was primary or
secondary. Hence the AMR rates were generalised to the whole study population. Also, the
sample comprised approximately 85% specimens from private institutions, therefore, might not
adequately represent resistance rates in public health settings. This was a retrospective study;
hence, some confounders, such as the change in the length of hospital stay, infection control
practices, and certain factors influencing antimicrobial resistance as mentioned above, could not
be evaluated. Therefore, multicenter and well-designed studies are required to substantiate the
present findings and elucidate the correlation between antibiotics consumption and antimicrobial
resistance.
Summary
Additionally, the development of a new rapid detection method for bacterial infection, which still
requires time-consuming procedures such as cultures, can represent an important tool to avoid
unnecessary or incorrect antibiotic prescriptions [39–41].
Conclusions
The increases registered suggest that efforts to control and prevent the spread of antibiotic-
resistant bacteria may need to be strengthened, such as through improved infection control
practices and appropriate use of antibiotics. It is also important to continue monitoring these
trends to track the effectiveness of interventions and to identify emerging resistance patterns. In
view of the increasing AMR issue worldwide and the current lack of new antimicrobials,
international solidarity is called for to fight against antimicrobial resistance and to sustain the
effectiveness of antimicrobials to treat bacterial infections for future generations.