https://doi.org/10.5812/archcid.86878

Investigation of Antimicrobial Susceptibilities Among Bacteria Isolated from Blood Cultures in Hospitalized Patients, Tehran, Iran

authors:

avatar Shadi Aghamohammad 1 , 2 , avatar Maryam Nouri ORCID 1 , avatar Fatemeh Ashrafian 1 , 3 , avatar Mohtaram Sadat Kashi 4 , avatar Mehrdad Gholami ORCID 5 , avatar Masoud Dadashi ORCID 6 , 7 , avatar Hossein Dabiri 1 , *

Department of Medical Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Department of Bacteriology, Pasteur Institute of Iran, Tehran, Iran
Microbiology Research Center (MRC), Pasteur Institute of Iran, Tehran, Iran
Loghman General Hospital, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Department of Microbiology and Virology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
Department of Microbiology, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran
Non-communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran
Archives of Clinical Infectious Diseases: Vol.16, issue 2; e86878
published online: June 8, 2021
article type: Research Article
received: November 28, 2018
revised: March 16, 2021
accepted: April 11, 2021

How To Cite Aghamohammad S, Nouri M, Ashrafian F, Kashi M S, Gholami M, et al. Investigation of Antimicrobial Susceptibilities Among Bacteria Isolated from Blood Cultures in Hospitalized Patients, Tehran, Iran. Arch Clin Infect Dis. 2021;16(2):e86878. https://doi.org/10.5812/archcid.86878.

Abstract

Background:

Bacteremia is the status, which is detected via a positive blood culture test with no contamination. Centers for Disease Control and Prevention (CDC) indicates that direct medical procedures and total costs are significantly high. Antibiotic resistance can play a major role in the costs, which are related to the long duration of treatment.

Objectives:

The aim of this study was to investigate the rate and profiles of antimicrobial susceptibility of blood culture isolates from Tehran, Iran.

Methods:

In the current cross-sectional study, a total of 5,000 blood culture samples were collected from patients hospitalized in the Loghman General Hospital, Tehran, Iran, with positive blood culture results from 2012 to 2013. Susceptibility to antimicrobial agents was analyzed using National Committee for Clinical Laboratory Standards guidelines.

Results:

Coagulase-negative staphylococci (38.8%), Staphylococcus aureus (20.5%), Acinetobacter (11.9%), and Escherichia coli (11.7%) were the most frequent bacteria isolated from the blood cultures, collectively accounting for > 80% of the isolates. Of isolated microorganisms, 63.75% and 36.24% belonged to Gram-positive and Gram-negative bacteria, respectively. Moreover, 88% of the isolates were MRSA (oxacillin-/methicillin-resistant), and 7% were VRE (vancomycin-resistant).

Conclusions:

The most frequent isolated organisms were Gram-positive bacteria, and the rate of MDR (multi-drug resistance) was high. The results of the current study obviously indicate the misuse of antibiotic in society. National surveillance studies in Iran will be useful for clinicians to choose the right empirical treatment and will help control and prevent infections caused by resistant organisms.

1. Background

Bacteremia is the status, which is detected via a positive blood culture test with no contamination. It can be ignored if the condition is transient without clinical manifestation (1). However, bloodstream infection (BSI) with symptoms like septic shock and multiple organ dysfunction syndromes can be more problematic (2). In fact, bacteremia can cause morbidity and mortality, especially in patients with underlying diseases e.g., patients on hemodialysis (3). Although blood culture is the gold standard method to detect bacteremia, using previous antibiotics can lead to false-negative results. Different classes of antibiotics are often used to treat bacteremia, specifically in ICU; however, studies revealed that more than 30% of antimicrobial agents are unsuitable. Increasing the rate of antimicrobial resistance (AMR) could increase the rate of morbidity and mortality or at least the cost of treatment (4). Centers for Disease Control and Prevention (CDC) indicates that US$90 million in direct medical procedures and US$230 in total costs are considered additional expenses. Most of the costs are related to the long duration of treatment due to using inappropriate antibiotics and hospitalization (5). The average hospital stays in ICU and wards for patients with bacteremia are 2 - 7 days and 2 - 3 weeks, respectively. As mentioned, AMR is challenging in treating patients with bacteremia, especially in microorganisms like Staphylococcus aureus (S. aureus). Antibiotic resistance in S. aureus has become a difficulty in the healthcare system since 1940. Besides, methicillin-resistance S. aureus (MRSA) has been detected since 1960 (6). Besides, MRSA isolates also can transfer antibiotic resistance to other genera (7, 8). Another antibacterial resistance, which has been significant since 1987, is vancomycin-resistant Enterococcus (VRE). Treatment of the bacteremia caused by VRE is complicated because the side effects of some antimicrobial agents such as chloramphenicol are problematic. Moreover, the rate of resistance to antibiotics, including ampicillin and aminoglycoside is high (9). Therefore, controlling the transmission of VRE isolates in hospitals is crucial (6). Different bacteria may be detected in blood culture (10). The bacteremia due to Enterobacteriaceae is associated with increased mortality compared with BSI caused by Gram-positive species (11). Among Gram-negative bacteria, Acinetobacter and Pseudomonas spp. can result in severe nosocomial bacteremia (12). On the other hand, in some regions, including Iran, CoNS (coagulase-negative staphylococci) and S. aureus are the most frequent organisms isolated from blood culture (13). The AMR is a critical consideration for physicians to choose a suitable regimen. This is particularly important for the treatment of systemic infections because initial antimicrobial chemotherapy is almost empiric, and it must be based on knowledge of their antimicrobial susceptibility patterns. Early initiation of appropriate antimicrobial treatment is critical to decreasing morbidity and mortality among patients with BSI (14).

2. Objectives

The aim of this study was to investigate the rate and profiles of antimicrobial susceptibility of blood culture isolates from Tehran, Iran.

3. Methods

3.1. Patients and Sample Collection

In the current cross-sectional study, a total of 5,000 blood culture samples were collected from patients hospitalized in the Loghman General Hospital, Tehran, Iran, with positive blood culture results from 2012 to 2013. Blood samples were collected through cleaning of the venous site with 70% alcohol and povidone-iodine. The blood sample was injected into brain heart infusion and sodium thioglycollate broths in the ratio of one part of a blood sample to five parts of the culture broth (15).

3.2. Bacteria Isolation and Identification

The blood culture broths were sent to the laboratory and incubated at 37°C for seven days. MacConkey, blood, and chocolate agar media were subcultured at 24, 72 hours and on the 7th day. Then they were incubated at the appropriate temperature and atmospheres according to standard procedures (16). Isolated organisms were identified by conventional biochemical methods.

3.3. Antibiotic Susceptibility Test

The susceptibilities of blood samples against 15 antibiotics: trimethoprim-sulfamethoxazole (SXT: 1.25/23.75 µg), cefotaxime (CTX: 30 µg), cefoperazone (CP: 75 µg), ceftazidime (CAZ: 30 µg), imipenem (IMP: 10 µg), ampicillin (AMP: 10 µg), gentamicin (GM: 30 µg), chloramphenicol (C: 30 µg ), penicillin (P: 10 µg), oxacillin (OX: 1 µg), clindamycin (CC: 2 µg), erythromycin (E: 15 µg), vancomycin (V: 30 µg), ofloxacin (OF: 5 µg), and amikacin (AK: 30 µg) (Mast Group Ltd., UK) were tested by agar disk-diffusion method according to clinical and laboratory standards institute (CLSI) guidelines (17). E. coli ATCC 25922 was used as a control for the disk diffusion method.

3.4. Statistical Analysis

Statistical analyses were performed using SPSS software (version 25; SPSS, Inc., Chicago, IL, USA). The Fisher's exact test or the chi-square test was applied to analyze categorical data. A P-values < 0.05 in all experiments were considered statistically significant.

4. Results

4.1. Results of Sample Collection

Of 5000 patients, 469 (9.3%) individuals had positive culture results. Also, 338 (72%) were male, and 131 (28%) were female. Of these 469 positive blood cultures, overall 469 isolates, 14 different species were detected. No mixed infection was observed. The most prevalent strains were CoNS (38.8%), S. aureus (20.5%), Acinetobacter (11.9%), and E. coli (11.7%). Pseudomonas, Enterobacter, Citrobacter, Proteus, Klebsiella, Salmonella, and Aeromonas spp. isolated in approximately 12% of cultures. Enterococcus and Streptococcus were found in 3% of positive cultures (Table 1). These results showed the predominance of bacteria, of which 63.75% and 36.24% were Gram-positive and Gram-negative bacteria, respectively.

Table 1.

Comparison of Distribution of Isolated Bacteria

Bacterial SpeciesNo. of Isolates% of Isolates
CoNS18238.8
Staphylococcus aureus9620.5
Acinetobacter spp.5611.9
E. coli5511.7
Klebsiella spp.224.7
Pseudomonas spp.173.6
Enterobacter spp.132.8
Streptococcus spp.112.3
Streptococcus pneumoniae61.3
Enterococcus40.9
Citrobacter spp.20.4
Proteus spp.20.4
Salmonella spp.20.4
Aeromonas spp.10.2
Total469100

4.2. Results of AMR Among Gram-Positive Bacteria

Sixty-two percent and 69% of CoNS were susceptible to gentamycin and fluoroquinolones, respectively, while 69% were resistant to cephalosporin. In addition, 88% of S. aureus isolates were MRSA, and 7% were VRE. Among Streptococcus spp., rather than enterococci and pneumococci, cefoperazone was active against 81% of isolates. Streptococcuspneumonia was highly susceptible to penicillin (75%) and resistant to trimethoprim-sulfamethoxazole (84%) (Table 2).

Table 2.

Frequency/Percentage of Gram-Positive Isolates Susceptible to Antimicrobial Agents

MicroorganismNO.VIPMCCGMCECPSXTAKAMCAZCTXOXPOF
CoNS18289464362362.5693219031211
S. aureus968663606239496962241501200
Streptococcus6911645182754813606305404536
S. pneumoniae228366330661683161650066075100
Enterococcus179325025502525002505002525

Abbreviations: SXT, trimethoprim-sulfamethoxazole; CTX, cefotaxime; CP, cefoperazone; CAZ, ceftazidime; IPM, imipenem; AK, amikacin; AM, ampicillin; GM, gentamicin; C, chloramphenicol; CC, clindamycin; E, erythromycin; V, vancomycin; P, penicillin; OX, oxacillin; OF, ofloxacin; CONS, coagulase-negative Staphylococcus aureus.

4.3. Results of AMR Among Gram-Negative Bacteria

As mentioned above, Acinetobacter spp. was the third common isolate. Moreover, 72 and 82% of isolates were resistant to imipenem, and amikacin, respectively, while 43% of Acinetobacter isolates were susceptible to cefoperazone. Further, 58 and 43% of E. coli were susceptible to amikacin, and gentamycin, respectively, and the rate of resistance to ceftazidime was 60%. The isolates of Klebsiella spp. were extremely resistant to more than three classes of antimicrobial agents, including cefotaxime (55%) (Table 3).

Table 3.

Frequency/Percentage of Gram-Negative Isolates Susceptible to Antimicrobial Agents

MicroorganismNO.VIPMCCGMCECPSXTAKAMCAZCTXOXPOF
Acinetobacter560280230043281801720000
E. coli550620430054325814029000
Klebsiella40680450064458146345000
Pseudomonas20590290065293552929000
Enterobacter11000847069776905469000
Citrobacter20100050005010050050100000
Proteus13050010000505050010050000
Salmonella20100010050010050100010050000
Aeromonas101000100001001001000050000

Abbreviations: SXT, trimethoprim-sulfamethoxazole; CTX, cefotaxime; CP, cefoperazone; CAZ, ceftazidime; IPM, imipenem; AK, amikacin; AM, ampicillin; GM, gentamicin; C, chloramphenicol; CC, clindamycin; E, erythromycin; V, vancomycin; P, penicillin; OX, oxacillin; OF, ofloxacin.

5. Discussion

The rate of bacteremia has been increased over the past years (1). Antimicrobial resistance (AMR) among bacteria isolated from blood culture is a worrying issue since it can influence the rate of mortality and morbidity (18). In Iran, AMR is a common cause of treatment failure of BSI. Since the determination of appropriate antibiotics is often not done in the best time, broad-spectrum antibiotics are used unnecessarily (19). Based on our results, Gram-positive organisms were the main pathogens (63.85%). Increasing rate of Gram-positive bacteria among blood cultures is seen in other regions (20). Bacteremia, which is caused by Gram-positive bacteria, is important because some microbial agents, including S. aureus, are often nosocomial and can make the situation of the patient more unfavorable. Besides, since some antimicrobial agents such as vancomycin has low tissue penetration, bacteremia caused by S. aureus often relapses (21). Increasing use of intravascular devices, as well as prolonged hospitalization, can result in raising the rate of the microorganisms, including CoNS and S. aureus (22). During the 1970s, BSI was most commonly associated with Gram-negative organisms, but recently, Gram-positive organisms began to emerge (23). This indicates that the organisms causing bacteremia are shifting toward Gram-positive in some regions (24). On the other hand, some studies reveal that Gram-negative bacteria remain predominant (25, 26). The critical issue is that Gram-negative bacteria can become problematic among patients with underlying diseases. Besides, previous use of antimicrobial agents in patients with underlying diseases can result in AMR among Gram-negative bacteria (27).

Besides the rates of MRSA, one of the most remarkable results in our study is high resistance to third-generation cephalosporins (3rd-GCs) among Gram-positive bacteria. Resistance to fluoroquinolone was almost variable among Gram-positive bacteria, which were 100% among S. aureus isolates and 0% among S. pneumonia. Furthermore, 3rd-GCs along with fluoroquinolones are generally used to treat BSI. As Lee et al. declared fluoroquinolones were more effective than 3rd-GCs for shortening the time of treatment of BSI (28); therefore, the high rate of susceptibility among S. pneumonia isolates can be considerable. Multi-drug resistance (MDR) is another issue that is important. All Gram-positive isolates were MDR, and specifically, the emergence of MDR among MRSA isolates can make the treatment more complicated and affect infection control in healthcare settings (29).

In addition, AMR was previously reported among Gram-negative bacteria (30, 31), which can be discussed from several points of view. Susceptibility to aminoglycoside was almost high among some Gram-negative isolates, including Salmonella, Aeromonas, Proteus, and Enterobacter. The effectiveness of aminoglycoside to treat the carbapenem-resistant isolates was studied in Shields et al. investigation (32). Some of the isolates showed high resistance to imipenem, including Enterobacter, which was susceptible to amikacin and gentamicin; therefore, it can give more chance to treat the patients more successfully. The rates of MDR isolates in Gram-negative bacteria are also impressive. Our Gram-negative isolates were totally resistant to ofloxacin, oxacillin, and clindamycin. The emergence of fluoroquinolone resistance along with beta-lactam drastically reduces the choice of treatment. Another important point is that previous use of antibiotics, including fluoroquinolone can influence increasing the rate of resistance in the future (33). Since the use of empirical antibiotics is a common way, previous use of antibiotics and subsequently the emergence of MDR can be threatening and challenging. The limitation of this study is the lack of molecular evaluation of antibiotics resistance-related genes, and it is suggested that minimal inhibitory concentration (MIC) and molecular tests should be performed for better assessment.

In conclusion, the results of current studies obviously indicate misuse of antibiotics in our society. National surveillance studies in Iran will be useful for clinicians to choose the right empirical treatment and will help control and prevent infections caused by resistant organisms.

References

  • 1.

    Nielsen SL, Lassen AT, Gradel KO, Jensen TG, Kolmos HJ, Hallas J, et al. Bacteremia is associated with excess long-term mortality: A 12-year population-based cohort study. J Infect. 2015;70(2):111-26. [PubMed ID: 25218427]. https://doi.org/10.1016/j.jinf.2014.08.012.

  • 2.

    Smith DA, Nehring SM. Bacteremia. StatPearls. Treasure Island (FL): StatPearls Publishing; 2021.

  • 3.

    Fram D, Okuno MF, Taminato M, Ponzio V, Manfredi SR, Grothe C, et al. Risk factors for bloodstream infection in patients at a Brazilian hemodialysis center: A case-control study. BMC Infect Dis. 2015;15:158. [PubMed ID: 25879516]. [PubMed Central ID: PMC4377039]. https://doi.org/10.1186/s12879-015-0907-y.

  • 4.

    Daneman N, Rishu AH, Xiong W, Bagshaw SM, Cook DJ, Dodek P, et al. Bacteremia antibiotic length actually needed for clinical effectiveness (BALANCE): Study protocol for a pilot randomized controlled trial. Trials. 2015;16:173. [PubMed ID: 25903783]. [PubMed Central ID: PMC4407544]. https://doi.org/10.1186/s13063-015-0688-z.

  • 5.

    Pai S, Enoch DA, Aliyu SH. Bacteremia in children: Epidemiology, clinical diagnosis and antibiotic treatment. Expert Rev Anti Infect Ther. 2015;13(9):1073-88. [PubMed ID: 26143645]. https://doi.org/10.1586/14787210.2015.1063418.

  • 6.

    Friedman ND, Temkin E, Carmeli Y. The negative impact of antibiotic resistance. Clin Microbiol Infect. 2016;22(5):416-22. [PubMed ID: 26706614]. https://doi.org/10.1016/j.cmi.2015.12.002.

  • 7.

    Armin S, Fallah F, Navidinia M, Vosoghian S. Prevalence of blaOXA-1 and blaDHA-1 AmpC β-lactamase-producing and methicillin-resistant Staphylococcus aureus in Iran. Arch Pediatr Infect Dis. 2017;5(4). e36778. https://doi.org/10.5812/pedinfect.36778.

  • 8.

    Navidinia M, Fallah F, Lajevardi B, Shirdoost M, Jamali J. Epidemiology of methicillin-resistant Staphylococcus aureus isolated from health care providers in Mofid Children Hospital. Arch Pediatr Infect Dis. 2015;3(2). e16458. https://doi.org/10.5812/pedinfect.16458.

  • 9.

    Patel R, Gallagher JC. Vancomycin-resistant enterococcal bacteremia pharmacotherapy. Ann Pharmacother. 2015;49(1):69-85. [PubMed ID: 25352037]. https://doi.org/10.1177/1060028014556879.

  • 10.

    Gandra S, Mojica N, Klein EY, Ashok A, Nerurkar V, Kumari M, et al. Trends in antibiotic resistance among major bacterial pathogens isolated from blood cultures tested at a large private laboratory network in India, 2008-2014. Int J Infect Dis. 2016;50:75-82. [PubMed ID: 27522002]. [PubMed Central ID: PMC5063511]. https://doi.org/10.1016/j.ijid.2016.08.002.

  • 11.

    Ma J, Li N, Liu Y, Wang C, Liu X, Chen S, et al. Antimicrobial resistance patterns, clinical features, and risk factors for septic shock and death of nosocomial E coli bacteremia in adult patients with hematological disease: A monocenter retrospective study in China. Medicine. 2017;96(21). e6959. [PubMed ID: 28538389]. [PubMed Central ID: PMC5457869]. https://doi.org/10.1097/MD.0000000000006959.

  • 12.

    Papadimitriou-Olivgeris M, Fligou F, Spiliopoulou A, Koutsileou K, Kolonitsiou F, Spyropoulou A, et al. Risk factors and predictors of carbapenem-resistant Pseudomonas aeruginosa and Acinetobacter baumannii mortality in critically ill bacteraemic patients over a 6-year period (2010-15): Antibiotics do matter. J Med Microbiol. 2017;66(8):1092-101. [PubMed ID: 28758623]. https://doi.org/10.1099/jmm.0.000538.

  • 13.

    Gitau W, Masika M, Musyoki M, Museve B, Mutwiri T. Antimicrobial susceptibility pattern of Staphylococcus aureus isolates from clinical specimens at Kenyatta National Hospital. BMC Res Notes. 2018;11(1):226. [PubMed ID: 29615129]. [PubMed Central ID: PMC5883409]. https://doi.org/10.1186/s13104-018-3337-2.

  • 14.

    Beganovic M, McCreary EK, Mahoney MV, Dionne B, Green DA, Timbrook TT. Interplay between rapid diagnostic tests and antimicrobial stewardship programs among patients with bloodstream and other severe infections. J Appl Lab Med. 2019;3(4):601-16. [PubMed ID: 31639729]. https://doi.org/10.1373/jalm.2018.026450.

  • 15.

    Snyder SR, Favoretto AM, Baetz RA, Derzon JH, Madison BM, Mass D, et al. Effectiveness of practices to reduce blood culture contamination: A Laboratory Medicine Best Practices systematic review and meta-analysis. Clin Biochem. 2012;45(13-14):999-1011. [PubMed ID: 22709932]. [PubMed Central ID: PMC4518453]. https://doi.org/10.1016/j.clinbiochem.2012.06.007.

  • 16.

    Garcia RA, Spitzer ED, Beaudry J, Beck C, Diblasi R, Gilleeny-Blabac M, et al. Multidisciplinary team review of best practices for collection and handling of blood cultures to determine effective interventions for increasing the yield of true-positive bacteremias, reducing contamination, and eliminating false-positive central line-associated bloodstream infections. Am J Infect Control. 2015;43(11):1222-37. [PubMed ID: 26298636]. https://doi.org/10.1016/j.ajic.2015.06.030.

  • 17.

    CLSI. Performance standards for antimicrobial susceptibility testing. 27th ed. Pennsylvania, USA: Clinical and Laboratory Standards Institute; 2017.

  • 18.

    De Angelis G, Fiori B, Menchinelli G, D'Inzeo T, Liotti FM, Morandotti GA, et al. Incidence and antimicrobial resistance trends in bloodstream infections caused by ESKAPE and Escherichia coli at a large teaching hospital in Rome, a 9-year analysis (2007-2015). Eur J Clin Microbiol Infect Dis. 2018;37(9):1627-36. [PubMed ID: 29948360]. https://doi.org/10.1007/s10096-018-3292-9.

  • 19.

    Salehi Nobandegani A, Motamedifar M. Antibiotic sensitivity profile of the bacterial isolates from the blood samples of the patients in different wards of a major referral hospital, Shiraz, Iran 2015-2016. Pharmacophores. 2019;10(2):30-6.

  • 20.

    Otto M. Staphylococcus epidermidis: A major player in bacterial sepsis? Future Microbiol. 2017;12:1031-3. [PubMed ID: 28748707]. [PubMed Central ID: PMC5627029]. https://doi.org/10.2217/fmb-2017-0143.

  • 21.

    Corey GR, Rubinstein E, Stryjewski ME, Bassetti M, Barriere SL. Potential role for telavancin in bacteremic infections due to Gram-positive pathogens: Focus on Staphylococcus aureus. Clin Infect Dis. 2015;60(5):787-96. [PubMed ID: 25472944]. [PubMed Central ID: PMC4329924]. https://doi.org/10.1093/cid/ciu971.

  • 22.

    Asaad AM, Ansar Qureshi M, Mujeeb Hasan S. Clinical significance of coagulase-negative staphylococci isolates from nosocomial bloodstream infections. Infect Dis. 2016;48(5):356-60. [PubMed ID: 26666168]. https://doi.org/10.3109/23744235.2015.1122833.

  • 23.

    Aamodt H, Mohn SC, Maselle S, Manji KP, Willems R, Jureen R, et al. Genetic relatedness and risk factor analysis of ampicillin-resistant and high-level gentamicin-resistant enterococci causing bloodstream infections in Tanzanian children. BMC Infect Dis. 2015;15:107. [PubMed ID: 25884316]. [PubMed Central ID: PMC4350950]. https://doi.org/10.1186/s12879-015-0845-8.

  • 24.

    Tang XJ, Sun B, Ding X, Li H, Feng X. Changing trends in the bacteriological profiles and antibiotic susceptibility in neonatal sepsis at a tertiary children's hospital of China. Transl Pediatr. 2020;9(6):734-42. [PubMed ID: 33457294]. [PubMed Central ID: PMC7804488]. https://doi.org/10.21037/tp-20-115.

  • 25.

    Pal N. Microbiological profile and antimicrobial resistant pattern of blood culture isolates, among septicaemia suspected patients. National Journal of Laboratory Medicine. 2016;5(1):17-21. https://doi.org/10.7860/njlm/2016/17494.2090.

  • 26.

    Le Doare K, Bielicki J, Heath PT, Sharland M. Systematic review of antibiotic resistance rates among Gram-negative bacteria in children with sepsis in resource-limited countries. J Pediatric Infect Dis Soc. 2015;4(1):11-20. [PubMed ID: 26407352]. https://doi.org/10.1093/jpids/piu014.

  • 27.

    Moghnieh R, Estaitieh N, Mugharbil A, Jisr T, Abdallah DI, Ziade F, et al. Third generation cephalosporin resistant Enterobacteriaceae and multidrug resistant Gram-negative bacteria causing bacteremia in febrile neutropenia adult cancer patients in Lebanon, broad spectrum antibiotics use as a major risk factor, and correlation with poor prognosis. Front Cell Infect Microbiol. 2015;5:11. [PubMed ID: 25729741]. [PubMed Central ID: PMC4325930]. https://doi.org/10.3389/fcimb.2015.00011.

  • 28.

    Lee CC, Wang JL, Lee CH, Hsieh CC, Hung YP, Hong MY, et al. Clinical benefit of appropriate empirical fluoroquinolone therapy for adults with community-onset bacteremia in comparison with third-generation-cephalosporin therapy. Antimicrob Agents Chemother. 2017;61(2). [PubMed ID: 27855072]. [PubMed Central ID: PMC5278695]. https://doi.org/10.1128/AAC.02174-16.

  • 29.

    Goudarzi M, Seyedjavadi SS, Nasiri MJ, Goudarzi H, Sajadi Nia R, Dabiri H. Molecular characteristics of methicillin-resistant Staphylococcus aureus (MRSA) strains isolated from patients with bacteremia based on MLST, SCCmec, spa, and agr locus types analysis. Microb Pathog. 2017;104:328-35. [PubMed ID: 28159661]. https://doi.org/10.1016/j.micpath.2017.01.055.

  • 30.

    Ashrafian F, Askari E, Kalamatizade E, Ghabouli-Shahroodi MJ, Naderi-Nasab M. The frequency of extended spectrum beta lactamase (ESBL) in Escherichia coli and Klebsiella pneumoniae: A report from Mashhad, Iran. J Med Bacteriol. 2013;2(1-2):12-9.

  • 31.

    Ashrafian F, Fallah F, Hashemi A, Erfanimanesh S, Amraei S, Tarashi S. First detection of 16S rRNA methylase and blaCTX-M-15 genes among Klebsiella pneumoniae strains isolated from hospitalized patients in Iran. Res Mol Med. 2015;3(4):28-34. https://doi.org/10.7508/rmm.2015.04.005.

  • 32.

    Shields RK, Clancy CJ, Press EG, Nguyen MH. Aminoglycosides for treatment of bacteremia due to carbapenem-resistant Klebsiella pneumoniae. Antimicrob Agents Chemother. 2016;60(5):3187-92. [PubMed ID: 26926642]. [PubMed Central ID: PMC4862490]. https://doi.org/10.1128/AAC.02638-15.

  • 33.

    Dan S, Shah A, Justo JA, Bookstaver PB, Kohn J, Albrecht H, et al. Prediction of fluoroquinolone resistance in Gram-negative bacteria causing bloodstream infections. Antimicrob Agents Chemother. 2016;60(4):2265-72. [PubMed ID: 26833166]. [PubMed Central ID: PMC4808151]. https://doi.org/10.1128/AAC.02728-15.