Scientifica

Scientifica / 2021 / Article

Research Article | Open Access

Volume 2021 |Article ID 5573345 | https://doi.org/10.1155/2021/5573345

Farzad Khademi, Amirhossein Sahebkar, "Is Penicillin-Nonsusceptible Streptococcus pneumoniae a Significant Challenge to Healthcare System? A Systematic Review and Meta-Analysis", Scientifica, vol. 2021, Article ID 5573345, 12 pages, 2021. https://doi.org/10.1155/2021/5573345

Is Penicillin-Nonsusceptible Streptococcus pneumoniae a Significant Challenge to Healthcare System? A Systematic Review and Meta-Analysis

Academic Editor: Abdel Halim Salem
Received14 Jan 2021
Accepted20 May 2021
Published27 May 2021

Abstract

Background. In recent years, antibiotic-resistant pathogens including penicillin-nonsusceptible Streptococcus pneumoniae (PNSP) have posed serious threats against human health. The aim of this meta-analysis was to investigate the prevalence of Streptococcus pneumoniae drug resistance particularly the incidence of PNSP strains in Iran. Methods. A systematic search was done in national and international electronic databases using Persian and English keywords. Up until May 20, 2020, a total of 58 publications were detected as eligible articles based on the inclusion and exclusion criteria, and then the selected studies were enrolled for data extraction and meta-analysis according to the PRISMA guidelines. Results. A high rate of PNSP (46.9%) and multidrug-resistant (MDR) S. pneumoniae (45.3%) in our isolates were evident. Furthermore, total frequency resistance to other drugs in S. pneumoniae was as follows: erythromycin 41.1%, azithromycin 53.2%, tetracycline 39.9%, levofloxacin 1.7%, rifampin 1.2%, clindamycin 31.7%, vancomycin 1.7%, trimethoprim/sulfamethoxazole 63.9%, chloramphenicol 20%, ceftriaxone 10.9%, amoxicillin 30.5%, ciprofloxacin 8.3%, imipenem 6.1%, linezolid 0%, and cefotaxime 8.3%. Conclusion. Although the overall prevalence of cephalosporin- and carbapenem-resistant Streptococcus pneumoniae was low, penicillin-resistant strains, especially PNSP, could become a significant challenge to the healthcare system in Iran. Hence, the prescription of penicillin as the first-choice antibiotic in the treatment of S. pneumoniae infections should be avoided.

1. Introduction

Streptococcus pneumoniae (S. pneumoniae) (pneumococcus) is a Gram-positive diplococcus that is an exclusively normal inhabitant in the oropharynx and nasopharynx of healthy individuals [1, 2]. Colonization rates are higher in the extreme of age (children under 5 and adults older than 65 years old) and immunocompromised patients especially in developing countries [3]. The bacterium enters the body through droplets and aerosols by person-to-person transmission. It then disseminates into other sites including circulation, brain, lungs, paranasal sinuses, and middle ears and causes severe diseases such as pneumonia, sinusitis, otitis media, bacteremia, and meningitis [13]. Pneumonia of any cause is an important disease affecting children under the age of five. In 2017, the World Health Organization (WHO) announced 808,694 pneumonia-related child deaths which accounts for 15% of total mortality in children younger than five years old [4]. The two most common bacterial causes of pneumonia in children are S. pneumoniae and Haemophilus influenzae type b, respectively [3]. Recently, a plan released by the WHO/UNICEF named the Integrated Global Action Plan for the Prevention and Control of Pneumonia and Diarrhea (GAPPD) with the aim of reducing the death rate to less than 3 children per 1000 live births by 2025 [4]. The main strategies to protect, prevent, and treat children with pneumococcal pneumonia include exclusive breastfeeding, adequate complementary feeding, hand washing, reducing household air pollution, prevention of HIV, oxygen therapy, vaccinations, and also the administration of appropriate antibiotics [4]. Potent anticapsular pneumococcal vaccines (PPSV23, PCV13, and PCV7) were developed based on the prevalent serotypes of S. pneumoniae; however, they are less effective in developing countries due to different distribution patterns of serotypes by geographic locations [1], and hence, they are not part of the childhood immunization plan in Iran. Over the last several decades, penicillin was the drug of choice for the treatment of pneumococcal diseases [1, 2]. However, up to 40% of these bacteria are found to be penicillin-resistant [5]. A list of antibiotic-resistant pathogens was released by WHO in February 2017 that urgently requires effective antibiotics [6]. Penicillin-nonsusceptible S. pneumoniae (PNSP) strains are priority 3 (medium) on the list and known as increasingly drug-resistant pathogens which require further research and development of new antibiotics [6]. Given the distinct geographical distributions, which can affect bacterial phenotypic and genetic characteristics such as drug susceptibility, and self-medication of antibiotics in Iran, the current systematic review and meta-analysis was performed to follow four objectives: (1) to estimate the overall prevalence of S. pneumoniae strains resistant to different antibiotics among all age groups in Iran, (2) to determine S. pneumoniae drug resistance in Iranian children, (3) to assess the prevalence of PNSP strains, and (4) to investigate antimicrobial resistance profiles in different provinces of Iran.

2. Methods

2.1. Search Strategies

The current systematic review and meta-analysis is designed based on the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines [7]. A comprehensive search was performed on studies published from October 1993 to May 2020. English keywords in the ISI Web of Knowledge, PubMed, Scopus, and Google Scholar databases and Persian keywords in national search engines including Scientific Information Database (http://www.sid.ir) and Magiran (http://www.Magiran.com) were used to find original articles addressing S. pneumoniae antibiotic resistance in Iran. For this purpose, the search terms (i.e., S. pneumoniae, antibiotic resistance, and Iran) were extracted from Medical Subject Headings (MeSH) and combined with connectors (AND/OR).

2.2. Inclusion and Exclusion Criteria

The articles were selected based on the title, abstract, and full text. First, the titles of cross-sectional studies on the prevalence of drug resistance were evaluated according to the author, bacterium, and country names, and then, abstracts and full texts were further assessed. Inclusion criteria were original articles assessing the prevalence of pneumococcus drug resistance, full-text availability, publication in English or Persian languages, and studies with sufficient data and limited to Iran. Exclusion criteria were studies reporting drug resistance patterns only at the level of Streptococcus genus or other than S. pneumoniae, evaluating the prevalence of S. pneumoniae resistance with low sample size, repetitive publications, nonoriginal articles, and articles available only in abstract form or abstracts from conferences.

2.3. Quality Assessment and Data Extraction

Included articles were further assessed in terms of quality using the Joanna Briggs Institute (JBI) critical appraisal checklist, and then, necessary data were extracted and tabulated in Table 1 [66]. The main data included the first author’s surname, study location, publication date, study enrollment date, age group, sample size, antibiotic susceptibility testing methods, the prevalence of S. pneumoniae resistance to different drugs, and the prevalence of multidrug-resistant (MDR) pneumococci.


Author (ref)ProvincePublished timeEnrollment timeAge groupStrain (n)ASTAntibiotic resistance (n)
PNSPERYAZMTETLVXRIFCLIVANSXTCHLCROAMXCIPIPMLZDCTXMDR

Gharibani et al. [8]Ardabil20192015Children43Disk diffusion4132311800120357NDNDNDNDNDND32
Khoshdel et al. [9]Chaharmahal and Bakhtiari20092007Children38Disk diffusion11NDNDNDNDNDNDNDNDNDNDNDNDNDNDNDND
Imani et al. [10]Chaharmahal and Bakhtiari20072005ND17Broth microdilution1610NDNDNDNDNDNDNDND1ND2NDNDNDND
Abdinia et al. [11]East Azerbaijan20142003–2013Children37Disk diffusion146NDNDND1ND01224ND3NDND3ND
Hadi and Bagheri [12]Fars20192011–2016Children10Disk diffusion73NDNDNDND30914NDNDNDNDNDND
Kargar et al. [13]Fars20152011–2012Children/adult45Disk diffusionNDNDNDND31NDNDNDNDNDNDND40NDNDNDND
Kargar et al. [14]Fars20122010–2011Children/adult50Disk diffusion30282252NDNDND240NDNDNDNDND2530
Shishegar et al. [15]Fars20112007–2008Children10Disk diffusionND1NDNDNDNDNDND10ND240NDND2ND
Japoni et al. [16]Fars20102005–2006ND13Disk diffusion53NDNDNDND1061NDND1NDNDNDND
Kohanteb and Sadeghi [17]Fars2007NDChildren/adult115Broth microdilution39211528NDNDND0ND97ND9NDND5ND
Ghaemi et al. [18]Golestan20021998–1999Children63Disk diffusion355ND23NDND13NDNDNDNDNDNDNDNDNDND
Khademi et al. [19]Hamadan20162013–2014Children/adult6Disk diffusionNDNDNDNDNDNDND03ND0ND1NDND0ND
Yousefi Mashouf et al. [20]Hamadan20142009–2013Children35Disk diffusionNDNDNDNDNDNDNDND912ND19NDNDNDNDND
Yousefi Mashouf et al. [21]Hamadan20031998–2000Children11Disk diffusionNDNDNDNDNDNDNDND34ND6NDNDNDNDND
Mosleh et al. [22, 23]Hamadan2014NDND55E-test521410NDNDNDND0NDNDNDND655NDND12
Yeganeh-Moghadam et al. [24]Isfahan20142011–2013Children15Disk diffusionND59NDNDNDNDND15ND990NDND9ND
Ghazikalayeh et al. [25]Isfahan20142011–2012Children291Disk diffusion4710ND740050NDNDNDNDNDND0NDND
Sabory et al. [26]Kermanshah20152012Children83Disk diffusionNDND53NDND34NDND31ND347NDNDNDND34
Khosravi et al. [27]Khuzestan20072005–2006Adult6Disk diffusionNDNDND3NDNDNDND0ND3NDNDNDNDNDND
Moafi and Issazadeh [28]Qazvin20162013–2014Children6Disk diffusionNDNDNDNDNDNDNDND44NDNDNDNDNDNDND
Mamishi et al. [29]Tehran20192017–2018Children4Disk diffusion14NDNDNDND201NDNDNDNDNDNDNDND
Ghahfarokhi et al. [30]Tehran20202015–2019Children/adult80Disk diffusion2949ND31NDND470571513NDNDNDNDND41
Azarsa et al. [31]Tehran20192015Children/adult46Disk diffusion12NDNDNDNDNDNDNDNDNDNDNDNDNDNDNDND
Mousavi et al. [32]Tehran20172014–2015Children76Disk diffusion7665654ND0NDNDNDNDNDNDNDNDNDND76
Ahmadi et al. [33]Tehran20192013–2016Children/adult100Disk diffusion2259ND57NDND49ND9223NDND3NDNDND54
Houri et al. [34]Tehran20172013–2016Children53Broth microdilution1115ND130NDND012ND4NDNDND039
Talebi et al. [35]Tehran20192013–2015ND161Disk diffusion9396ND121NDND84ND15195NDNDNDNDNDND69
Moghadam et al. [36]Tehran20172013–2015Children/adult100Disk diffusion2664ND770ND56096440NDND00ND71
Farshad et al. [37]Tehran20162013Adult48Disk diffusion40NDNDNDNDNDNDNDNDNDNDNDNDNDNDNDND
Rahbar et al. [38]Tehran20192012–2016Children/adult50E-test153635281ND2603213NDNDNDNDNDNDND
Tabatabaei et al. [39]Tehran20172012–2015Children/adult73Broth microdilution1661NDNDNDNDND011ND23NDNDNDND31ND
Talebi et al. [40]Tehran20162011–2013Children/adult100Disk diffusion2860ND85NDND780934800ND00050
Azadegan et al. [41]Tehran20152011–2013Children/adult186Disk diffusionND88ND186NDNDNDNDNDNDNDNDNDNDNDNDND
Abdollahi et al. [42]Tehran20182011–2012Children102Disk diffusion6124ND110NDND07023NDNDNDNDND0ND
Ahmadi et al. [43]Tehran20132011Children/adult88Disk diffusionND47ND55NDNDNDNDNDNDNDNDNDNDNDNDND
Soltan Dallal et al. [44]Tehran20132011Children/adult15Disk diffusion1210ND0NDNDND8ND8ND12NDNDNDNDND
Sadeghi et al. [45]Tehran20152010–2012Children/adult80E-test36NDNDNDNDNDNDNDNDNDNDNDNDNDNDNDND
Ahmadi et al. [46]Tehran20152010–2012Children/adult70Disk diffusion60NDNDNDNDNDNDNDNDNDNDNDNDNDNDNDND
Mahmoudi et al. [47]Tehran20132009–2011Children7Disk diffusion5NDNDNDNDNDNDND7ND4NDNDNDNDNDND
Khoramrooz et al. [48]Tehran20122009–2010Children23Disk diffusion61113ND0ND8023ND3ND0ND0NDND
Rahimi et al. [49]Tehran20152008–2012Children/adult38NA32ND8NDNDND2294NDND6NDNDNDND
Habibian et al. [50]Tehran20132008–2012ND50Broth microdilution9NDNDNDNDNDND4NDNDNDND2NDNDNDND
Dashti et al. [51]Tehran20122008–2009Children573Disk diffusion53ND315377ND0ND9683426239NDND17ND
Ashtiani et al. [52]Tehran20142001–2011Children194Disk diffusion8999NDNDNDNDND01395823NDNDNDND25ND
Pourakbari et al. [53]Tehran20122001–2005Children46Disk diffusion1429NDNDNDND3ND388NDNDNDNDNDNDND
Aligholi et al. [54]Tehran20092001–2005Children50Agar dilution1529NDNDND0ND0NDND0ND15NDNDNDND
Oskoui et al. [55]Tehran20102000–2008ND54Disk diffusion389ND10NDNDNDND28NDNDNDNDNDND29
Jahanmehr et al. [56]Tehran20041999–2001ND66Disk diffusion12NDNDNDNDNDND0NDNDND12NDNDNDNDND
Oskoui et al. [57]Tehran20031998–2000ND130Disk diffusion11410ND47NDNDND05728NDNDNDNDNDNDND
Rezaeizadeh et al. [58]Tehran20121998–2008Children30Disk diffusion176NDNDNDNDND0196NDNDNDNDNDNDND
Modarres et al. [59]Tehran19981993–1995Children51Disk diffusion11NDNDNDNDND29342NDNDNDNDNDNDND
Gharailoo et al. [60]Sistan and Balouchastan20162013–2014Children42Disk diffusion4223ND260NDND0396ND7NDNDND0ND
Bokaeian et al. [61]Sistan and Balouchastan20122008–2010Children75Disk diffusion6266ND430NDND047120NDND0NDND43
Bokaeian et al. [62]Sistan and Balouchastan20112007–2008Children/adult136Broth microdilution4325ND13NDNDND0ND115ND2NDND318
Rahbar et al. [63]West Azerbaijan20051999–2001ND24Disk diffusion8NDNDNDNDND000NDNDND0NDNDNDND
Behnaz et al. [64]Yazd20042002Children72Disk diffusion3645ND22NDNDNDND45NDNDNDNDNDNDNDND
Karami et al. [65]Zanjan20092006–2007Children/adult57Broth macrodilution33NDNDNDNDNDND0NDNDNDNDNDNDNDNDND

PNSP: penicillin-nonsusceptible S. pneumoniae (intermediately resistant and fully resistant); ERY: erythromycin; AZM: azithromycin; TET: tetracycline; LVX: levofloxacin; RIF: rifampin; CLI: clindamycin; VAN: vancomycin; SXT: trimethoprim/sulfamethoxazole; CHL: chloramphenicol; CRO: ceftriaxone; AMX: amoxicillin; CIP: ciprofloxacin; IPM: imipenem; LZD: linezolid; CTX: cefotaxime; MDR: multidrug-resistant (resistant to ≥3 antibiotic classes); AST: antimicrobial susceptibility testing; ND: not determined.
2.4. Meta-Analysis

Meta-analysis of the extracted data on the S. pneumoniae antibiotic resistance was performed using the Comprehensive Meta-Analysis (CMA) software (Biostat, Englewood, NJ), and the frequency of drug resistance was expressed as the percentage and 95% confidence intervals (95% CIs). Further analysis on the location of the study and age groups was also conducted. To evaluate the heterogeneity across the included studies, I2 statistics and the chi-square test (χ2) with the Cochrane Q statistic (Q test) ( value <0.05 was considered statistically significant) were used. A random-effects model (DerSimonian–Laird method) was used to pool the data when heterogeneity was considered high (I2 ≥ 25%). Distribution bias among published studies was calculated quantitatively using Begg’s and Egger’s tests ( value <0.05 indicates a significant bias) and visualized via the funnel plot graphs for each antibiotic.

3. Results

3.1. Results of Search and Characteristics of the Included Articles

Data were available from 15 provinces as follows: Ardabil (n = 1), Chaharmahal and Bakhtiari (n = 2), East Azerbaijan (n = 1), Fars (n = 6), Golestan (n = 1), Hamadan (n = 5), Isfahan (n = 2), Kermanshah (n = 1), Khuzestan (n = 1), Qazvin (n = 1), Tehran (n = 31), Sistan and Balouchastan (n = 3), West Azerbaijan (n = 1), Yazd (n = 1), and Zanjan (n = 1). Detailed characteristics of the selected articles are summarized in Table 1. A total of 1249 reports were identified for the analysis of S. pneumoniae antibiotic resistance in Iran. Finally, 58 articles (50 in English and 8 in Persian) were included in the study (Figure 1). Disk diffusion, E-test, and broth micro- and macrodilution were the most common methods used for antimicrobial susceptibility testing in the included articles.

3.2. Total S. pneumoniae Drug Resistance in Iran

The pooled prevalence of S. pneumoniae resistance to various antibiotics including erythromycin, azithromycin, tetracycline, levofloxacin, rifampin, clindamycin, vancomycin, trimethoprim/sulfamethoxazole, chloramphenicol, ceftriaxone, amoxicillin, ciprofloxacin, imipenem, linezolid, and cefotaxime was 41.1% (95% CI: 32.9–49.7; I2 = 93%; Q = 545.1; ), 53.2% (95% CI: 38.9–67.1; I2 = 92.4%; Q = 118.4; ), 39.9% (95% CI: 30.2–50.4; I2 = 95%; Q = 506.8; ), 1.7% (95% CI: 0.2–11.1; I2 = 90.9%; Q = 110; ), 1.2% (95% CI: 0.1–13.2; I2 = 91.1%; Q = 67.6; ), 31.7% (95% CI: 20.7–45.2; I2 = 91.9%; Q = 172.8; ), 1.7% (95% CI: 0.7–4.1; I2 = 85.8%; Q = 218.4; ), 63.9% (95% CI: 52.3–74; I2 = 94.6%; Q = 672.5; ), 20% (95% CI: 14.2–27.3; I2 = 91.4%; Q = 303.5; ), 10.9% (95% CI: 6.6–17.6; I2 = 84.7%; Q = 130.8; ), 30.5% (95% CI: 12.8–56.8; I2 = 95.2%; Q = 187.6; ), 8.3% (95% CI: 3.6–17.7; I2 = 89.6%; Q = 154.3; ), 6.1% (95% CI: 0.1–89.4; I2 = 91.8%; Q = 36.6; ), 0%, and 8.3% (95% CI: 3.7–17.4; I2 = 92.5%; Q = 189; ), respectively. The frequency of MDR S. pneumoniae strains in Iran was 45.3% (95% CI: 34.3–56.8; I2 = 91.3%; Q = 150.7; ). As illustrated in Figure 2, the prevalence of MDR S. pneumoniae in Iran showed an increasing trend from 16.7% in 2010 to 51.3% in 2020. A random-effects model was used to estimate pooled effect in terms of the heterogeneity among studies.

3.3. S. pneumoniae Drug Resistance in Different Provinces of Iran

The results of the subgroup analysis of the prevalence of S. pneumoniae antibiotic resistance based on the different geographic locations in Iran are shown in Table 2. A random-effects model was used to combine studies within each subgroup and obtain the overall effect. The highest rates of S. pneumoniae antibiotic resistance among different provinces in Iran were as follows: 74.4% to erythromycin in Ardabil, 72.1% to azithromycin in Ardabil, 50% to tetracycline in Khuzestan, 24.2% to levofloxacin in Fars, 41% to rifampin in Kermanshah, 50.1% to clindamycin in Tehran, 2.5% to vancomycin in Hamadan, 96.9% to trimethoprim/sulfamethoxazole in Isfahan, 66.7% to chloramphenicol in Qazvin, 60% to ceftriaxone in Isfahan, 60% to amoxicillin in Isfahan, 20.1% to ciprofloxacin in Fars, 99.1% to imipenem in Hamadan, and 60% to cefotaxime in Isfahan. In addition, the highest rates of PNSP and MDR S. pneumoniae strains were detected in Ardabil (95.3% and 74.4%, respectively).


ProvinceAntibiotic resistance (%)
PNSPERYAZMTETLVXRIFCLIVANSXTCHLCROAMXCIPIPMLZDCTXMDR

Ardabil95.374.472.141.91.11.127.91.181.416.3NDNDNDNDNDND74.4
Chaharmahal and Bakhtiari69.258.8NDNDNDNDNDNDNDND5.9ND11.8NDNDNDND
East Azerbaijan37.816.2NDNDND2.7ND1.332.45.410.8ND8.1NDND8.1ND
Fars48.627.425.51724.2ND18.51.966.27.317.14020.1NDND18.660
Golestan55.67.9ND36.5NDND20.6NDNDNDNDNDNDNDNDNDND
Hamadan94.525.518.2NDNDNDND2.529.134.87.154.311.699.1ND7.121.8
Isfahan16.211.46025.40.20.21.70.296.9ND60603.1ND060ND
KermanshahNDND63.9NDND41NDND37.3ND3.656.6NDNDNDND41
KhuzestanNDNDND50NDNDNDND7.1ND50NDNDNDNDNDND
QazvinNDNDNDNDNDNDNDND66.766.7NDNDNDNDNDNDND
Tehran40.247.368.145.71.10.450.12.269.524.19.812.85.90.505.447
Sistan and Balouchastan79.355.4ND38.10.9NDND0.781.312.12.616.71.50.7ND231.2
West Azerbaijan33.3NDNDNDNDND20.22NDNDND2NDNDNDND
Yazd5062.5ND30.6NDNDNDND62.5NDNDNDNDNDNDNDND
Zanjan57.8NDNDNDNDNDND0.9NDNDNDNDNDNDNDNDND

3.4. S. pneumoniae Drug Resistance in Iranian Children

The results of subgroup analysis based on the age group indicated that 27 studies investigated the prevalence of S. pneumoniae antibiotic resistance profiles in Iranian children. Based on the current meta-analysis, S. pneumoniae resistance to different antibiotics was as follows: 38.5% (95% CI: 25.7–53.2; I2 = 93.4%; Q = 290.2; ) to erythromycin, 66.5% (95% CI: 54.8–76.5; I2 = 81%; Q = 26.4; ) to azithromycin, 33% (95% CI: 20.2–49; I2 = 95.9%; Q = 223.1; ) to tetracycline, 0.8% (95% CI: 0.3–2.1; I2 = 0.0%; Q = 1.9; ) to levofloxacin, 1.2% (95% CI: 0.1–13.2; I2 = 91.1%; Q = 67.6; ) to rifampin, 17.3% (95% CI: 7.3–35.6; I2 = 86.8%; Q = 45.5; ) to clindamycin, 1.7% (95% CI: 0.4–7.1; I2 = 90.7%; Q = 151; ) to vancomycin, 63.7% (95% CI: 48.3–76.7; I2 = 94.8%; Q = 407.2; ) to trimethoprim/sulfamethoxazole, 17.7% (95% CI: 11.4–26.3; I2 = 86.1%; Q = 93.6; ) to chloramphenicol, 12.6% (95% CI: 6.5–22.9; I2 = 84.9%; Q = 73; ) to ceftriaxone, 35.1% (95% CI: 12.3–67.6; I2 = 96.3%; Q = 162.4; ) to amoxicillin, 5.5% (95% CI: 1.1–22.7; I2 = 90.7%; Q = 53.7; ) to ciprofloxacin, 0.7% (95% CI: 0.0–9.7; I2 = 0.0%; Q = 0.0; ) to imipenem, 0% to linezolid, and 8.3% (95% CI: 3.2–19.8; I2 = 88.6%; Q = 61.4; ) to cefotaxime. Besides, 57.4% (95% CI: 33.1–78.6; I2 = 91%; Q = 44.8; ) of S. pneumoniae isolated from Iranian children were MDR strains. Random- or fixed-effects models were used to estimate pooled effect.

3.5. Penicillin-Nonsusceptible S. pneumoniae in Iran

According to the random-effects model (I2 = 93.6%; Q = 712.6; ), the total prevalence of PNSP strains in Iran was 46.9% (95% CI: 38.6–55.4). In addition, the rate of PNSP strains isolated from Iranian children was 46.9% (95% CI: 33.4–60.8; I2 = 94.4%; Q = 363.1; ) as well (Figure 3(a)). As shown in Figure 3(b), publication bias was detected in the current study due to the evidence of asymmetry in the funnel plot whereas the results of Begg’s (z = 0.21, ) and Egger’s tests (t = 1.86, ) were not statistically significant. Finally, as presented in Figure 2, we assessed the frequency of PNSP strains from 1998 to 2020. Figure 2 shows an increasing trend of PNSP strains in Iran.

4. Discussion

Antibiotic resistance is consistently growing and has become a global public health crisis. According to the European Center for Disease Prevention and Control (ECDC) and the Center for Disease Control and Prevention (CDC), antibiotic-resistant bacteria in Europe and the USA are associated with an annual mortality rate of 25,000 and 23,000, respectively. Also, nearly 700,000 deaths worldwide are due to antibiotic resistance [5, 67]. It is estimated that antimicrobial resistance will lead to 10 million deaths a year by 2050 [5, 67]. Factors such as antibiotic overuse/misuse in humans and also in the food/veterinary industry along with reduced development of new antibiotics play key roles in the incidence of both Gram-positive and Gram-negative resistant bacteria [5]. Penicillin-resistant S. pneumonia was first detected in Australia in 1967. PNSP strains are listed as one of the most serious emerging bacterial threats as of 2017 [3, 6]. The current rate of penicillin-resistant S. pneumoniae in Iran is 46.9%, whereas it is found to be 1–5% in the UK, Germany, Austria, Norway, and Sweden, 5–10% in Italy, 10–25% in Portugal, Ireland, Finland, and Turkey, 25–50% in Spain, France, Greece, and Israel, 20% in Brazil, and 66.4% in China [6870]. The results of subgroup analysis based on the age group showed a similarly high rate of PNSP among Iranian children (46.9%) which could be due to the common use of antibiotics in these patients [39]. Therefore, the prescription of penicillin as the first-choice antibiotic in the treatment of S. pneumoniae infections such as meningitis and pneumonia should be avoided. The prevalence of PNSP isolates in Iran has shown a rising trend from 1998 to 2020 (Figure 2). While there was high pneumococcal resistance to amoxicillin in Iran, resistance to other beta-lactam antibiotics such as cephalosporins and carbapenems was rather low. Thus, the extended-spectrum cephalosporins are suitable alternative drugs in the treatment of penicillin-resistant infections including pneumococcal meningitis in Iran. Modification of penicillin-binding proteins (PBPs) particularly PBP1a, PBP2x, and PBP2b as well as mutations in cpoA, ciaH, murM, and murN genes has been described as the main mechanisms of resistance in S. pneumoniae to beta-lactam antibiotics [3]. Pneumococcal resistance to macrolides, fluoroquinolones, and tetracyclines has also been reported [1]. The prevalence of macrolide-resistant S. pneumoniae is geographically variable as it ranges from 25 to 50% in France, Italy, and Greece, 10 to 25% in Spain, Portugal, the UK, Germany, Poland, Norway, and Finland, and 1 to 5% in Latvia and Sweden [68]. In Iran, 41.1% and 53.2% of S. pneumoniae isolates were resistant to erythromycin and azithromycin, respectively. Ribosomal modification, efflux system, and point mutations are involved in the emergence of macrolide-resistant S. pneumoniae [3]. An important mechanism of S. pneumoniae resistance to clindamycin is the alteration of the ribosomal target through erm(B) gene which encodes a 23S RNA methylase [71]. Clindamycin has shown a strong activity against community-acquired infections of S. pneumoniae [71]. However, the rates of clindamycin-resistant pneumococcal strains in the current study were high (31.7%) and included 25% in Egypt, 35.1% in Turkey, and 21.8% in the United States [3,71]. Penicillins and macrolides have been largely applied in the treatment of community-acquired pneumonia and other respiratory tract infections by S. pneumoniae [72]. However, a high resistance rate to these antibiotics has led to the use of quinolones against important bacterial respiratory tract pathogens [72]. Hence, a combination of vancomycin and gentamicin is proposed for treating infections caused by penicillin- and cephalosporin-resistant S. pneumoniae strains [3]. The findings of the present study on the prevalence of fluoroquinolone-resistant strains of S. pneumoniae indicated a low resistance rate to levofloxacin (1.7%) and ciprofloxacin (8.3%) in Iran. The prevalence of fluoroquinolone-resistant pneumococcal strains in other countries was as follows: 4% in Egypt, 1.8% in Turkey, 1-2% in the USA, and <10% in Belgium [3, 71, 72]. A low incidence of vancomycin-resistant S. pneumoniae was found in Iran (1.7%), and no resistance has been reported in many other countries [3]. Factors associated with resistance to fluoroquinolones in clinical pneumococcal isolates include mutations in the quinolone-resistance-determining regions (QRDRs) of gyrA, gyrB, parC, and parE genes as well as the overexpression of pmrA gene (codes for an efflux pump) and patA and patB genes (code for an ABC transporter) [3, 71]. Point mutation in a histidine kinase gene (vncS) is associated with the emergence of vancomycin-tolerant pneumococcal strains [3]. The highest drug resistance rate among pneumococcal isolates in Iran was observed to folate pathway inhibitors (i.e., trimethoprim/sulfamethoxazole (63.9%)). Cotrimoxazole-resistant S. pneumoniae were isolated in 25–45% of strains in the USA, 55% in Egypt, 100% in Saudi Arabia, and 67.2% in Turkey [3, 71]. Mutations in dihydrofolate reductase (DHFR) and in dihydropteroate synthase (DHPS) are the mechanisms of resistance to folate inhibitors [3, 71]. Studies from the Middle East and the USA have reported a high rate of S. pneumoniae resistance to tetracycline which could be attributed to extensive use of this antimicrobial agent [3, 71]. A similar result was observed in the current study (39.9%). Resistance to chloramphenicol (a bacterial protein inhibitor) was high whereas there was no resistance to linezolid. Two other important findings of the study included a high prevalence of MDR pneumococci in Iranian people (45.3%), especially children (57.4%) with a rising trend from 2010 to 2020 (Figure 2), and also the isolation of S. pneumoniae resistant to many drugs (such as erythromycin, azithromycin, tetracycline, trimethoprim/sulfamethoxazole, and amoxicillin) in Iranian children. Available data from CDC showed that MDR S. pneumoniae is responsible for more than 30% of invasive pneumococcal disease throughout the United States [73, 74]. Therefore, timely vaccination in Iranian children and ongoing surveillance on drug resistance trend along with the use of combination therapy or the use of newer antibiotics are needed to improve microorganism susceptibility.

5. Conclusion

The current study indicated a high prevalence of PNSP and MDR strains in Iran among all age groups. Similar results were also observed in the frequency of erythromycin-, azithromycin-, tetracycline-, clindamycin-, trimethoprim/sulfamethoxazole-, chloramphenicol-, and amoxicillin-resistant S. pneumoniae strains. These findings could be due to the high consumption of nonprescribed antibiotics in Iran. Hence, strategies to prevent emerging drug-resistant pneumococcal infections and treatment failure in Iran include (1) continuous regional monitoring of nasopharyngeal carriers of antibiotic-resistant S. pneumoniae in children, (2) controlled administration of antibiotics to improve microorganism susceptibility, (3) use of combination therapies or drugs with low resistance rate in accordance with local resistance patterns, and (4) identification of the most common pneumococcal serotypes and their drug resistance rates in Iranian population to produce effective pneumococcal vaccines. The most effective antibiotics for the treatment of pneumococcal infections in Iran based on the current study are levofloxacin, rifampin, vancomycin, ceftriaxone, ciprofloxacin, imipenem, linezolid, and cefotaxime.

Data Availability

There are no raw data associated with this systematic review and meta-analysis.

Conflicts of Interest

The authors declare that there are no conflicts of interest.

References

  1. P. R. Murray, K. S. Rosenthal, and M. A. Pfaller, Medical Microbiology, Elsevier Health Sciences, London, UK, 8th edition, 2015.
  2. K. C. Carroll, J. S. Butel, and S. A. Morse, Jawetz Melnick & Adelbergs Medical Microbiology, McGraw Hill Professional, New York, NY, USA, 27 edition, 2016.
  3. G. El Moujaber, M. Osman, R. Rafei, F. Dabboussi, and M. Hamze, “Molecular mechanisms and epidemiology of resistance in Streptococcus pneumoniae in the Middle East region,” Journal of Medical Microbiology, vol. 66, no. 7, pp. 847–858, 2017. View at: Publisher Site | Google Scholar
  4. World Health Organization, Pneumonia, WHO, Geneva, Switzerland, 2014, http://www.who.int/mediacentre/factsheets/fs331/en/.
  5. M. S. Morehead and C. Scarbrough, “Emergence of global antibiotic resistance,” Primary Care: Clinics in Office Practice, vol. 45, no. 3, pp. 467–484, 2018. View at: Publisher Site | Google Scholar
  6. World Health Organization, WHO Publishes List of Bacteria for Which New Antibiotics Are Urgently Needed, WHO, Geneva, Switzerland, 2017.
  7. A. Liberati, D. G. Altman, J. Tetzlaff et al., “The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration,” PLoS Medicine, vol. 6, no. 7, Article ID e1000100, 2009. View at: Publisher Site | Google Scholar
  8. K. M. Gharibani, A. Azami, M. Parvizi, F. Khademi, S. F. Mousavi, and M. Arzanlou, “High frequency of macrolide-resistant Streptococcus pneumoniae colonization in respiratory tract of healthy children in Ardabil, Iran,” Tanaffos, vol. 18, no. 2, pp. 118–125, 2019. View at: Google Scholar
  9. A. Khoshdel, R. Imani, A. Saedi et al., “The prevalence of Streptococcus pneumonia and its penicillin resistance pattern in children less than five years old from Shahrekord, Iran, 2007,” Journal of Shahrekord University of Medical Sciences, vol. 10, no. 4, pp. 89–95, 2009. View at: Google Scholar
  10. R. Imani, H. Rouhi-Boroujeni, and F. Ganji, “Prevalence of antibiotic resistance among bacteria isolates of lower respiratory tract infection in COPD Shahrekord Iran, 2005,” Pakistan Journal of Medical Sciences, vol. 23, no. 3, pp. 438–440, 2007. View at: Google Scholar
  11. B. Abdinia, M. A. Rezaee, and S. A. Oskouie, “Etiology and antimicrobial resistance patterns of acute bacterial meningitis in children: a 10-year referral hospital-based study in northwest Iran,” Iranian Red Crescent Medical Journal, vol. 16, no. 7, Article ID e17616, 2014. View at: Publisher Site | Google Scholar
  12. N. Hadi and K. Bagheri, “A five-year retrospective multicenter study on etiology and antibiotic resistance pattern of bacterial meningitis among Iranian children,” Infection Epidemiology and Microbiology, vol. 5, no. 4, pp. 17–24, 2019. View at: Google Scholar
  13. M. Kargar, F. M. Jahromi, A. Doosti, Z. Mohammadalipour, and S. Lorzadeh, “Resistance to different generations of quinolones in Streptococcus pneumoniae strains isolated from hospitals in Shiraz,” Comparative Clinical Pathology, vol. 24, no. 3, pp. 533–536, 2015. View at: Publisher Site | Google Scholar
  14. M. M. Kargar, M. Baghernejad, S. Ghorbani-Dalini, and A. Najafi, “Multi-drug resistance and molecular pattern of erythromycin and penicillin resistance genes in Streptococcus pneumoniae,” African Journal of Biotechnology, vol. 11, no. 4, pp. 968–973, 2012. View at: Google Scholar
  15. M. Shishegar, A. Faramarzi, T. Kazemi, A. Bayat, and M. Motamedifar, “Polymerase chain reaction, bacteriologic detection and antibiogram of bacteria isolated from otitis media with effusion in children, Shiraz, Iran,” Iranian Journal of Medical Sciences, vol. 36, no. 4, pp. 273–280, 2011. View at: Google Scholar
  16. A. Japoni, M. Kalani, S Farshad et al., “Antibiotic-resistant bacteria in hospitalized patients with bloodstream infections: analysis of some associated factors,” Iranian Red Crescent Medical Journal, vol. 12, no. 2, pp. 163–171, 2010. View at: Google Scholar
  17. J. Kohanteb and E. Sadeghi, “Penicillin-resistant Streptococcus pneumoniae in Iran,” Medical Principles and Practice, vol. 16, no. 1, pp. 29–33, 2007. View at: Publisher Site | Google Scholar
  18. E. E. Ghaemi, M. Fazeli, A. Tabaraei, and M. Vakili, “The prevalence of pneumococci throat carrier in healthy school children in Gorgan,” Journal of Urmia University of Medical Sciences, vol. 13, no. 1, pp. 16–24, 2002, in Persian. View at: Google Scholar
  19. F. Khademi, A. A. Yousefi, A. Yousefi, P. Karami, K. Ghazvini, and F. Ghanbari, “Prevalence and antimicrobial susceptibility patterns of bacteria isolated from different clinical infections in hamadan, Iran,” Infection, Epidemiology and Medicine, vol. 2, no. 3, pp. 8–13, 2016. View at: Publisher Site | Google Scholar
  20. R. Yousefi Mashouf, R. Esmaeili, and A. Moshtaghi, “Study of bacterial agents of meningitis in children and detection of their antibiotic resistance patterns in hamadan, Western Iran,” International Journal of Medical Investigation, vol. 3, no. 1, pp. 18–24, 2014. View at: Google Scholar
  21. R. Yousefi Mashouf, H. Hashemi, and S. Shams, “Study of bacterial agents of meningitis in children and detection of antibiogram patterns in Hamadan,” YAFTEH, vol. 5, no. 17, pp. 31–37, 2004, in Persian. View at: Google Scholar
  22. M. N. Mosleh, M. Gharibi, M. Y. Alikhani, M. Saidijam, and F. Vakhshiteh, “Antimicrobial susceptibility and analysis of macrolide resistance genes in Streptococcus pneumoniae isolated in Hamadan,” Iranian Journal of Basic Medical Sciences, vol. 17, pp. 595–599, 2014. View at: Google Scholar
  23. M. N. Mosleh, M. Gharibi, M. Y. Alikhani, M. Saidijam, and G. Kalantarian, “Antimicrobial susceptibilities and distribution of resistance genes for β-lactams in Streptococcus pneumoniae isolated in Hamadan,” Jundishapur Journal of Microbiology, vol. 7, no. 10, Article ID e12714, 2014. View at: Google Scholar
  24. A. Yeganeh-Moghadam, M. Namazi, S. A. Moravveji, A. Khorshidi, and A. Abbasi-Moghadam, “Bacteriological assessment of resistant effusional otitis media discharge among the 2-16 year-old children admitted to Matini hospital in Kashan, 2011-2013,” Feyz Journal of Kashan University of Medical Sciences, vol. 18, no. 5, pp. 469–476, 2014, in Persian. View at: Google Scholar
  25. H. M. Ghazikalayeh, R. Moniri, S. G. Moosavi, M. Rezaei, M. Yasini, and M. Valipour, “Serotyping, antibiotic susceptibility and related risk factors aspects of nasopharyngeal carriage of Streptococcus pneumoniae in healthy school students,” Iranian Journal of Public Health, vol. 43, no. 9, pp. 1284–1290, 2014. View at: Google Scholar
  26. T. Sabory, K. Ghadiri, R. Abiri, A. Elahi, S. Poormohammadi, and A. R. Gharib, “Incidence of nasopharyngeal carriers of Streptococcus pneumoniae and antibiotic resistance in the children in Kermanshah 2012,” Journal of Nursing Education - Healio, vol. 4, no. 4, pp. 90–97, 2016, in Persian. View at: Google Scholar
  27. A. D. Khosravi, M. Mehdinejad, and M. Heidari, “Bacteriological findings in patients with ocular infection and antibiotic susceptibility patterns of isolated pathogens,” Singapore Medical Journal, vol. 48, no. 8, pp. 741–743, 2007. View at: Google Scholar
  28. N. Moafi and K. Issazadeh, “Frequency of Neonatal and children bacterial meningitis and determining their antibiotic sensitivity patterns in Hospitals of Iran,” International Journal of Molecular and Clinical Microbiology, vol. 6, no. 1, pp. 608–612, 2016. View at: Google Scholar
  29. S. Mamishi, M. Mohammadian, B. Pourakbari et al., “Antibiotic resistance and genotyping of gram-positive bacteria causing hospital-acquired infection in patients referring to children's medical center,” Infection and Drug Resistance, vol. 12, pp. 3719–3726, 2019. View at: Publisher Site | Google Scholar
  30. S. H. Ghahfarokhi, M. Mosadegh, A Ahmadi et al., “Serotype distribution and antibiotic susceptibility of Streptococcus pneumoniae isolates in Tehran, Iran: a surveillance study,” Infection and Drug Resistance, vol. 13, pp. 333–340, 2020. View at: Google Scholar
  31. M. Azarsa, S. Ohadian Moghadam, M. Rahbar, Z. Baseri, and M. R. Pourmand, “Molecular serotyping and genotyping of penicillin non-susceptible pneumococci: the introduction of new sequence types, Tehran, Iran,” New Microbes and New Infections, vol. 32, Article ID 100597, 2019. View at: Publisher Site | Google Scholar
  32. S. F. Mousavi, B. Mirzaei, B. Shaghaghi, P. Jalali, T. Setayesh, and S. H. Moosavi, “Phenotypic and genotypic features of first biofilm forming nasopharyngeal colonized Streptococcus pneumoniae isolates,” Iranian Journal of Microbiology, vol. 9, no. 4, pp. 200–207, 2017. View at: Google Scholar
  33. A. Ahmadi, S. Yaghoubi, and G. Irajian, “Molecular analysis of PBP1A inStreptococcus pneumoniaeIsolated from clinical and normal flora samples in Tehran, Iran: a multicenter study,” Microbial Drug Resistance, vol. 25, no. 1, pp. 39–46, 2019. View at: Publisher Site | Google Scholar
  34. H. Houri, S. R. Tabatabaei, Y. Saee, F. Fallah, M. Rahbar, and A. Karimi, “Distribution of capsular types and drug resistance patterns of invasive pediatric Streptococcus pneumoniae isolates in Teheran, Iran,” International Journal of Infectious Diseases, vol. 57, pp. 21–26, 2017. View at: Publisher Site | Google Scholar
  35. M. Talebi, J. Sadeghi, A. Ahmadi, V. Lohrasbi, P. Owlia, and M. R. Pourshafie, “High rate of serotype switching and genetic variations indicates Widespread recombination between clinical and commensal penicillin-nonsusceptible Streptococcus pneumoniae in Tehran,” Microbial Drug Resistance, vol. 25, no. 6, pp. 865–873, 2019. View at: Publisher Site | Google Scholar
  36. M. S. Moghadam, M. Talebi, F. Masjedian, G. Irajian, and M. R. Pourshafie, “Streptococcus pneumoniae serotyping by a single polymerase chain reaction–based multiplex assay,” Infectious Diseases in Clinical Practice, vol. 26, no. 2, pp. 75–79, 2018. View at: Google Scholar
  37. A. A. Farshad, M. Enferadi, S. Bakand, R. Jamshidi Orak, and R. Mirkazemi, “Penicillin dust exposure and penicillin resistance among pharmaceutical workers in Tehran, Iran,” International Journal of Occupational and Environmental Health, vol. 22, no. 3, pp. 218–223, 2016. View at: Publisher Site | Google Scholar
  38. M. Rahbar, A. Dolatyar Dehkharghani, S. M. Zahraei, M. Mardani, and M. Mohammadzadeh, “Antimicrobial resistance in Streptococcus pneumoniae isolates from invasive pneumococcal infections in Iran,” Journal of Global Antimicrobial Resistance, vol. 16, pp. 260-261, 2019. View at: Publisher Site | Google Scholar
  39. S. R. Tabatabaei, M. Rahbar, A. N Alam et al., “Detection of pbp2b gene and antimicrobial susceptibility pattern of Streptococcus pneumoniae isolates in Tehran hospitals, Iran,” Archives of Pediatric Infectious Diseases, vol. 5, no. 1, Article ID e38891, 2017. View at: Google Scholar
  40. M. Talebi, A. Azadegan, J Sadeghi et al., “Determination of characteristics of erythromycin resistant Streptococcus pneumoniae with preferred PCV usage in Iran,” PLoS One, vol. 11, no. 12, Article ID e0167803, 2016. View at: Publisher Site | Google Scholar
  41. A. Azadegan, A. Ahmadi, A. R. Lari, and M. Talebi, “Detection of the efflux-mediated erythromycin resistance transposon in Streptococcus pneumoniae,” Annals of Laboratory Medicine, vol. 35, no. 1, pp. 57–61, 2015. View at: Publisher Site | Google Scholar
  42. S. Abdollahi, S. D. Siadat, R Shapouri et al., “Antibiotic susceptibility and prevalence of adhesion genes in Streptococcus pneumoniae isolates detected in carrier children in Tehran,” Jundishapur Journal of Microbiology, vol. 11, no. 6, Article ID e13256, 2018. View at: Publisher Site | Google Scholar
  43. A. Ahmadi, M. Talebi, and G. Irajian, “High prevalence of erythromycin- and tetracycline-resistant clinical isolates of Streptococcus pneumoniae in Iran,” Infectious Diseases in Clinical Practice, vol. 21, no. 5, pp. 299–301, 2013. View at: Publisher Site | Google Scholar
  44. M. M. Soltan Dallal, H. Jabbari, A. Rahimi Forushani, S. Heidarzadeh, P. Afrogh, and M. K. Sharifi Yazdi, “Frequency and resistance patterns of Streptococcus pneumoniae in acute otitis media,” Journal of Mazandaran University of Medical Sciences, vol. 23, no. 98, pp. 28–35, 2013, in Persian. View at: Google Scholar
  45. J. Sadeghi, A. Ahamadi, M. Douraghi, M. R. Pourshafie, and M. Talebi, “Molecular analysis of pbp2b in Streptococcus pneumonia isolated from clinical and normal flora samples,” Current Microbiology, vol. 70, no. 2, pp. 206–211, 2015. View at: Publisher Site | Google Scholar
  46. A. Ahmadi, M. Esghaei, G. Irajian, and M. Talebi, “Differentiation of penicillin susceptible and nonsusceptible Streptococcus pneumoniae,” Journal of Medical Bacteriology, vol. 4, no. 1-2, pp. 15–20, 2015. View at: Google Scholar
  47. S. Mahmoudi, H. Zandi, B. Pourakbari, M. T. H. Ashtiani, and S. Mamishi, “Acute bacterial meningitis among children admitted into an Iranian referral children's hospital,” Japanese Journal of Infectious Diseases, vol. 66, no. 6, pp. 503–506, 2013. View at: Publisher Site | Google Scholar
  48. S. S. Khoramrooz, A. Mirsalehian, M. Emaneini et al., “Frequency of Alloicoccus otitidis, Streptococcus pneumoniae, Moraxella catarrhalis and Haemophilus influenzae in children with otitis media with effusion (OME) in Iranian patients,” Auris Nasus Larynx, vol. 39, no. 4, pp. 369–373, 2012. View at: Publisher Site | Google Scholar
  49. F. Rahimi, M. N. Hashemian, A. Khosravi, G. Moradi, and S. Bamdad, “Bacterial keratitis in a tertiary eye centre in Iran: a retrospective study,” Middle East African Journal of Ophthalmology, vol. 22, no. 2, pp. 238–244, 2015. View at: Publisher Site | Google Scholar
  50. S. Habibian, A. Mehrabi-Tavana, Z Ahmadi et al., “Serotype distribution and antibiotics susceptibility pattern of Streptococcus pneumonia in Iran,” Iranian Red Crescent Medical Journal, vol. 15, no. 10, Article ID e8053, 2013. View at: Publisher Site | Google Scholar
  51. A. Sanaei Dashti, B. Abdinia, and A. Karimi, “Nasopharyngeal carrier rate of Streptococcus pneumoniae in children: serotype distribution and antimicrobial resistance,” Archives of Iranian Medicine, vol. 15, no. 8, pp. 500–503, 2012. View at: Google Scholar
  52. M. T. Ashtiani, M. Sadeghian, B. Nikmanesh, B. Pourakbari, S. Mahmoudi, and S. Mamishi, “Antimicrobial susceptibility trends among Streptococcus pneumoniae over an 11-year period in an Iranian referral children hospital,” Iran Journal of Microbiology, vol. 6, no. 6, pp. 382–386, 2014. View at: Google Scholar
  53. B. Pourakbari, A. Sadr, M. T Ashtiani et al., “Five-year evaluation of the antimicrobial susceptibility patterns of bacteria causing bloodstream infections in Iran,” Journal of Infection in Developing Countries, vol. 6, no. 02, pp. 120–125, 2012. View at: Publisher Site | Google Scholar
  54. M. Aligholi, M. Emaneini, F Jabalameli et al., “Antibiotic susceptibility pattern of gram-positive cocci cultured from patients in three university hospitals in Tehran, Iran during 2001–2005,” Acta Medica Iranica, vol. 47, no. 4, pp. 329–334, 2009. View at: Google Scholar
  55. M. Oskoui, S. Nobari, F. Rahmati Ghezelgeh, B. Shaghaghi, and N. Amirmozafari, “Molecular characterization of PBP2b in clinical isolates of Streptococcus pneumoniae,” Iranian Journal of Medical Microbiology, vol. 4, no. 1 and 2, pp. 9–16, 2010, in Persian. View at: Google Scholar
  56. S. A. H. Jahanmehr, A. Rajabi, M. Soltani Radd, and G. H. Behzadian Nejad, “The resistance of Streptococcus pneumoniae against penicillin and other antibiotics,” Acta Medica Iranica, vol. 42, no. 3, pp. 223–227, 2004. View at: Google Scholar
  57. M. Oskoui, M. Feyzabadi, and A. Amirkhani, “Drug susceptibility of Streptococcus pneumoniae strains isolated in Tehran, Iran,” Archives of Iranian Medicine, vol. 6, no. 3, pp. 192–195, 2003. View at: Google Scholar
  58. G. Rezaeizadeh, B. Pourakbari, M. H. Ashtiani, F. Asgari, S. Mahmoudi, and S. Mamishi, “Antimicrobial susceptibility of bacteria isolated from cerebrospinal fluids in an Iranian referral pediatric center, 1998-2008,” Maedica, vol. 7, no. 2, pp. 131–137, 2012. View at: Google Scholar
  59. S. H. Modarres, A. Lasheii, and N. N. Oskoii, “Bacterial etiologic agents of ocular infection in children in the Islmic Republic of Iran,” East Mediterr Health Journal, vol. 4, no. 1, pp. 44–49, 1998. View at: Google Scholar
  60. Z. Gharailoo, S. F. Mousavi, N. Halvani, and M. M. Feizabadi, “Antimicrobial resistant pattern and capsular typing of Streptococcus pneumoniae isolated from children in Sistan–Baluchestan,” Mædica., vol. 11, no. 3, pp. 203–207, 2016. View at: Google Scholar
  61. M. Bokaeian, H. A. Khazaei, and M. Javadimehr, “Serotype distribution and antimicrobial resistance of invasive Streptococcus pneumoniae isolates from children in Zahedan, Iran,” African Journal of Microbiology Research, vol. 6, no. 1, pp. 28–33, 2012. View at: Google Scholar
  62. M. Bokaeian, H. A. Khazaei, and M. Javadimehr, “Nasopharyngeal carriage, antibiotic resistance and serotype distribution of Streptococcus pneumoniae among healthy adolescents in Zahedan,” Iranian Red Crescent Medical Journal, vol. 13, no. 5, pp. 328–333, 2011. View at: Google Scholar
  63. M. Rahbar, R. Gra-Agaji, and S. Hashemi, “Nosocomial blood stream infections in Imam Khomeini hospital, Urmia, Islamic Republic of Iran, 1999-2001,” Eastern Mediterranean health journal = La revue de sante de la Mediterranee orientale = al-Majallah al-sihhiyah li-sharq al-mutawassit, vol. 11, no. 3, pp. 478–484, 2005. View at: Google Scholar
  64. F. Behnaz, L. Firousabadi, A. Babaei-Zadeh, and M. Mohammad - Zadeh, “Prevalence of pharyngeal pneumococcal carriers and succeptibility patterns among children of day care centers in Yazd district, Iran,” JSSU, vol. 12, no. 1, pp. 65–69, 2004, in Persian. View at: Google Scholar
  65. A. Karami, M. Panahi, and A. Karami, “Determination of pneumococcal MIC to antibiotics in pneumococcus strains isolated from Zanjan hospitals,” JQUMS, vol. 13, no. 2, pp. 17–22, 2009, in Persian. View at: Google Scholar
  66. Z. Munn, S. Moola, K. Lisy, D. Riitano, and C. Tufanaru, “Methodological guidance for systematic reviews of observational epidemiological studies reporting prevalence and cumulative incidence data,” International Journal of Evidence-Based Healthcare, vol. 13, no. 3, pp. 147–153, 2015. View at: Publisher Site | Google Scholar
  67. S. J. Hoffman, K. Outterson, J.-A. Røttingen et al., “An international legal framework to address antimicrobial resistance,” Bull World Health Organ, vol. 93, p. 66, 2016. View at: Google Scholar
  68. R. R. Reinert, “The antimicrobial resistance profile of Streptococcus pneumoniae,” Clinical Microbiology and Infection, vol. 15, no. Suppl. 3, pp. 7–11, 2009. View at: Publisher Site | Google Scholar
  69. T. C. Pinto, F. P. Neves, A. R Souza et al., “Evolution of penicillin non-susceptibility among Streptococcus pneumoniae isolates recovered from asymptomatic carriage and invasive disease over 25 years in Brazil, 1990-2014,” Frontiers in Microbiology, vol. 10, p. 486, 2019. View at: Publisher Site | Google Scholar
  70. C. Zhao, Z. Li, F Zhang et al., “Serotype distribution and antibiotic resistance of Streptococcus pneumoniae isolates from 17 Chinese cities from 2011 to 2016,” BMC Infect Dis, vol. 17, no. 1, p. 804, 2017. View at: Publisher Site | Google Scholar
  71. R. Cherazard, M. Epstein, T.-L. Doan, T. Salim, S. Bharti, and M. A. Smith, “Antimicrobial resistant Streptococcus pneumoniae: prevalence, mechanisms, and clinical implications,” American Journal of Therapeutics, vol. 24, no. 3, pp. e361–e369, 2017. View at: Publisher Site | Google Scholar
  72. P. J. Ceyssens, F. Van Bambeke, W Mattheus et al., “Belgian Streptococcus pneumoniae Study Group. Molecular analysis of rising fluoroquinolone resistance in Belgian non-invasive Streptococcus pneumoniae isolates (1995-2014),” PLoS One, vol. 11, no. 5, Article ID e0154816, 2016. View at: Publisher Site | Google Scholar
  73. Centers for Disease Control and Prevention, Antibiotic Resistance Threats in the United States, Centers for Disease Control and Prevention, Atlanta, GA, USA, 2019.
  74. S. B. Levy and B. Marshall, “Antibacterial resistance worldwide: causes, challenges and responses,” Nature Medicine, vol. 10, no. 12, pp. S122–S129, 2004. View at: Publisher Site | Google Scholar

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