









































Pa
ge

 
1



Pa
ge

 
91

American Journal of  Medical 
Science and Innovation (AJMSI) 

Gram-Negative Bacteremia: Epidemiology and Antimicrobial Resistance in Qatar
Adila Shaukat1*, Masautso Chaponda1, Walid Al-Wali2, Farah Maher3, Sara Al-Balushi4, Abdulmajeed Maliyakkal5, Israa Elhakeem5 

Tahani Al-Saadi2, Ali Omrani1, Muna Al Maslamani1

Volume 3 Issue 2, Year 2024
ISSN: 2836-8509 (Online)

DOI: https://doi.org/10.54536/ajmsi.v3i2.3181
https://journals.e-palli.com/home/index.php/ajmsi

Article Information ABSTRACT

Received: September 05, 2024 

Accepted: October 02, 2024 

Published: October 05, 2024

One of  the major causes of  morbidity and mortality in hospitalised patients is the 
presence of  gram-negative bacteremia (GNB) in blood. The developed resistance among 
the bacteria poses a significant challenge for treatment. The study aimed to identify the 
gram-negative patient’s epidemiological risk factors, antimicrobial susceptibility patterns, 
and clinical outcomes. A retrospective observational study of  adult in-patients with gram-
negative bacteremia was conducted between January 2019 and December 2020 in the 
320-bed general hospital in Qatar. Data on demographics, antimicrobial resistance, source
of  infection, and treatment were collected. The primary outcomes were patients’ cure,
death, or relapse. Total of  357 patients were identified with bacteremia, the most common
sources being urinary tract infections (39.6%), intra-abdominal infections (28%), and lower
respiratory tract infections (9%). The mean duration of  the intravenous and oral antibiotics
administration was 14 days. Surgical source control was performed in 35.7% of  patients.
Common pathogens were Escherichia-coli (47.2%), Klebsiella pneumoniae (16.4%), Salmonella
enterica serotype Typhi (10.6%), and Pseudomonas aeruginosa (7.8%). 67.32% fully susceptible
strains, 31.56% extended-spectrum beta-lactamase (ESBL) producing bacteria, and 1.11%
multidrug-resistant organisms (MDROs) were among the isolates. Most infections (68%)
were cured, but 5% had recurrence within 90 days of  admission. Infection-related mortality
was 8%, and death due to non-infectious causes was 2%. In conclusion, Gram-negative BSIs 
are severe infections with increasing antimicrobial resistance, primarily caused by ESBL-
producing bacteria. High mortality rates are linked to diabetes, age, and hospitalisation,
necessitating antibiotic treatment optimisation.

Keywords
Antimicrobial Resistance, Clinical 
Outcomes, Epidemiology, ESBL-
Producing Bacteria, Gram-
Negative Bacteremia

1 Infectious Disease Department, Hamad Medical Corporation, Qatar & Qatar University, College of  Medicine, Qatar
2 Microbiology Department, Hamad Medical Corporation, Qatar  
3 Pharmacy Department, Hamad Medical Corporation, Qatar
4 Epidemiology Department, CDC, Hamad Medical Corporation, Qatar
5 Medicine Department, Hamad Medical Corporation, Qatar
* Corresponding author’s e-mail: adilazia44@gmail.com

INTRODUCTION
Gram-negative bacteria are known to cause a range of  
infections, including urinary tract infections, biliary 
infections, pneumonia, and primary and secondary 
bloodstream infections (Gajdács et al., 2019; Kim & Park, 
2018; Kwiecińska-Piróg et al., 2018). Factors that predispose 
to these infections include extreme age, comorbidities 
such as diabetes mellitus, immunosuppression, prior use 
of  antimicrobials, medical device usage, and invasive 
interventions such as surgery, nosocomial acquisition, 
and duration of  stay, even though without a predisposing 
factor, the infection may also arise (Gajdács et al., 2019). 
One of  the major factors contributing to the mortality 
and morbidity of  hospitalised patients is gram-negative 
bacteremia (GNB). These patients require prompt 
diagnosis and appropriate antibiotic therapy. The initiation 
of  appropriate antibiotics can reduce mortality, treatment 
failure, and length of  stay, highlighting the importance 
of  broad-spectrum empirical therapy, diagnostic 
stewardship, and rapid diagnostics for early and timely 
identification  (Bassetti et al., 2020; Gajdács et al., 2019). 
Conflicting observations have resulted in uncertainty 
concerning the optimum duration of  antibiotic therapy 
for bacteremia caused by gram-negative infections. Many 

believe gram-negative bacteremia patients should be 
treated with a 10-14-day intravenous antibiotics course to 
prevent serious sequelae, such as abscess formation and 
relapse (Turjeman et al., 2023). Recently, Lee et al. (2019) 
and Yahav et al. (2019) have suggested that short therapy 
courses are adequate for uncomplicated bacteremia 
(Lee et al., 2019; Yahav et al., 2019). The emerging 
resistance among these bacteria significantly challenges 
healthcare delivery (Iskandar et al., 2021). Infections by 
antimicrobial-resistant organisms, particularly multidrug-
resistant organisms (De Waele et al., 2018), could result 
in treatment failure, increased morbidity and mortality, 
increased medical costs, prolonged hospital stays, and 
increased socioeconomic burden (Iskandar et al., 2021; 
Kitaya et al., 2023). 
In high resistance rates, selecting appropriate 
empiric antibiotic treatment for suspected gram-
negative infections is difficult (Fitzpatrick et al., 2016). 
Inappropriate empirical antimicrobial therapy has been 
shown to predict death in critically ill patients (Turjeman 
et al., 2023). Furthermore, prolonged antimicrobial 
exposure is associated with adverse effects, increased rates 
of  Clostridioides difficile infection, antimicrobial resistance, 
and longer hospital stays (Dyer et al., 2019).



Pa
ge

 
92

https://journals.e-palli.com/home/index.php/ajmsi

Am. J. Med. Sci. Innov. 3(2) 91-102, 2024

Different centres vary depending on the patient 
population, immune status, infection control precautions, 
and antimicrobial use (Spellberg & Rice, 2019). Analysis 
of  local trends and epidemiology is necessary to optimise 
empirical antibiotic treatment (Yahav et al., 2019). If  
indicated, appropriate antimicrobial therapy with source 
control is warranted to achieve optimal outcomes 
(Turjeman et al., 2023). The study aims to identify the local 
epidemiologically predisposing factors, antimicrobial 
susceptibility patterns, and clinical outcomes in adult 
patients with gram-negative bacteremia, focusing on 
factors associated with morbidity and mortality.

MATERIALS AND METHODS
Study Design and Selection Criteria
A retrospective cohort study was conducted on in-patient 
adults with gram-negative bacteremia between January 
2019 and December 2020 in a 320-bed general hospital 
in Qatar. All adult patients who presented with gram-
negative bacteremia during the study period based on 
positive blood cultures were identified retrospectively 
from the Microbiology Lab through hospital electronic 
records. Pediatric patients (aged <14 years) and transit 
passengers were excluded from the study. Samples 
considered contaminants, as determined by the clinical 
picture and subsequent management, were also not 
included.
A Microbiology database was used to record antimicrobial 
susceptibility testing current guidelines from the Clinical 
and Laboratory Standards Institute (CLSI) (Iskandar et 
al., 2021). The hospital’s electronic patient record system 
was used to capture all clinical data related to these 
patients. In contrast, the demographic details, including 
age, sex, comorbidities (immunosuppression, malignancy, 
pregnancy, renal disease, diabetes, and hypertension), 
and clinical presentation, were also recorded. A need for 
admission to the critical care unit was used to assess the 
severity of  infection. The probable source of  infection, 
persistence of  bacteremia beyond the first blood culture, 
and therapeutic options with intravenous antibiotics 
alone or combined with source control (incision and 
drainage of  abscesses, stent insertion) were examined. 
The choice of  antibiotics and duration of  treatment, 
including changes made according to sensitivity, were also 
recorded. Clinical outcomes were gauged as cure, death, 
or infection recurrence within 90 days of  admission. 
Any subsequent development of  alert organisms such as 
Clostridium difficile infection or the emergence of  multidrug-
resistant microorganisms 90 days after admission was 
also monitored. Multidrug resistance (MDR) was defined 
as resistance to at least one agent from three or more 
antimicrobial classes (Yezli et al., 2014).

Ethical Approval
This study was approved by the Institutional Review 
Board (IRB) and Medical Research and Ethics Committee 
Hamad Medical Corporation (Protocol ID MRC-01-21-
259). However, this retrospective cohort review did not 
obtain individual patient consent.

Statistical Analysis
Statistical analysis was conducted on 358 patients using 
the Sata/Se 14.2. The study analysed epidemiological 
data, including descriptive statistics and continuous and 
categorical variables. Categorical variables were presented 
as counts and percentages, whereas normal continuous 
variables are expressed as means and standard deviations, 
and non-normal variables are presented as medians and 
interquartile ranges (IQR). The Shapiro-Wilk test and 
visual inspection of  histograms were employed to assess 
the normality of  the data. The student’s t-test was applied 
to normal outcomes, the Mann-Whitney test was applied 
to non-normal outcomes, and the chi-square test was used 
for categorical variables. Survival analysis was performed 
using Kaplan-Meier survival curves and the log-rank test 
to assess the differences between the groups for variables 
associated with mortality based on univariate analysis.

RESULTS AND DISCUSSIONS
The demographic and clinical characteristics of  the 
cohort with gram-negative bacteremia were analysed, with 
a total of  358 patients included in the study. Among these 
patients, the majority (218, 60.8%) were male, with a mean 
age of  51. Table 1 describes the comorbidities observed in 
the study population. Notably, diabetes mellitus emerged 
as a significant confounding factor. Patients’ demographic 
and clinical profiles were stratified based on their diabetes 
status, resulting in 197 non-diabetic patients (Non-
DM) and 160 diabetes patients (DM). The non-diabetic 
group exhibited a significantly younger age than the 
diabetic group (median ages of  42.5 vs. 60, respectively, 
p < 0.001). Furthermore, hypertension, end-stage renal 
disease on hemodialysis, and chronic kidney disease 
were more prevalent in the diabetic group compared to 
the non-diabetic group (p < 0.001 for all). Although the 
length of  hospital stay did not differ significantly between 
the two groups (p = 0.94), primary bacteremia was more 
common in the non-diabetic group (p = 0.038). Bacterial 
isolates also showed significant differences in prevalence, 
particularly with E. coli, Klebsiella, and Salmonella Typhi. 
Additionally, the source of  bacteremia varied significantly 
between the groups, with urinary tract and intra-abdominal 
infections being prominent in both. Antibiotic resistance 
did not notably differ between the groups (p = 0.49), As 
shown in Table 1.

Table 1: Baseline characteristics of  the study population by diabetes status
 Non-DM (n = 197) DM (n = 160)  
Demographics 
Age (Wilcoxon rank) 42.00  (28.00-54.00) 60.00 (49.50-70.00) <0.001



Pa
ge

 
93

https://journals.e-palli.com/home/index.php/ajmsi

Am. J. Med. Sci. Innov. 3(2) 91-102, 2024

Male 128     (64.65%) 90 (56.25%) 0.093
Comorbidities
HTN 37       (18.76%) 115 (71.88%) <0.001 
ESRD HD 07       (3.55%) 25 (15.63%) <0.001  
CKD 11       (5.58%) 33 (20.63%) <0.001  
Malignancy 26      (13.20%) 9 (5.63%) 0.012 
COPD/Asthma 12      (6.09%) 12 (7.50%) 0.59 
HIV 0        (0.00%) 1 (0.63%)
IHD 7        (3.55%) 38 (23.75%) <0.001 
HF 10      (5.08%) 13 (8.13%) 0.24 
Liver disease 9        (4.57%) 13 (8.13%) 0.16 
Pregnant females (Fisher's exact) 7 (10.14 %) 1 (1.43 %) 0.063 
Valvular disease (Fisher’s exact) 3 (1.52%) 10 (6.25%)  0.017
Cystic fibrosis 0 (0%) 0 (0%)  
Inflammatory bowel disease (Fisher's exact) 0 (0.00%) 1 (0.63%) 0.45
Tuberculosis 1 (0.51%) 0 (0.00%) 1 
Immunosuppressive treatment 15 (7.61%) 9 (5.63%) 0.46
Long hospital stays 10 (5.08%) 12 (7.50%) 0.34
Complicated bacteremia 51 (25.89%) 53 (33.13%) 0.16
Persistence 13 (6.60%) 5 (3.13%) 0.15
Intubated 31 (15.74%) 29 (18.13%) 0.56
ICU 52 (26.40%) 39 (24.38%) 0.61
Readmission 25 (12.69%) 23 (14.37%) 0.88
Length of  stay (Wilcoxon rank) 35.00 (16.00-44.00) 33.00 (12.00-46.00) 0.94
Emergence 7 (3.55%) 15 (9.38%) 0.05
C. diff 2 (1.02%) 0 (0.00%) 0.63
Source control   0.046
Yes 81 (41.12%) 47 (29.38%)  
Unknown 36 (18.27%) 42 (26.25%)  
Abs Previous 36 (18.27%) 63 (39.38%) <0.001
Completed IV   0.008
In-patient 128 (64.97%) 106 (66.25%)  
MHS 17 (8.63%) 29 (18.13%)  
OPAT 47 (23.86%) 24 (15.00%)  
Unknown 5 (2.54%) 1 (0.63%)  
Microbiology 
Primary bacteremia 75 (38.07%) 44 (27.50%) 0.038 
Community-acquired bacteremia 157 (79.70%) 131 (81.88%)  
Bacterial isolates   0.004
Acinetobacter 3 (1.52%) 5 (3.13%)  
Brucella 6 (3.03%) 2 (1.25%)  
Citrobacter 1 (0.51%) 1 (0.63%)  
E. coli 90 (45.45%) 79 (49.38%)  
Enterobacter cloacae 6 (3.03%) 2 (1.25%)  
Klebsiella 28 (14.14%) 31 (19.38%)  
Non-typhoidal Salmonella 5 (2.53%) 0 (0.00%)  
Proteus 2 (1.01%) 4 (2.50%)  
Pseudomonas 12 (6.06%) 15 (9.38%)  



Pa
ge

 
94

https://journals.e-palli.com/home/index.php/ajmsi

Am. J. Med. Sci. Innov. 3(2) 91-102, 2024

Figure 1 shows that 68% of  patients with gram-negative 
bloodstream infections (GNB) successfully recovered 
from sepsis, but 8% succumbed to sepsis, 5% experienced 
recurrence, and 6% died from unrelated causes. 5% 
showed multidrug-resistant organisms, indicating 

antimicrobial resistance. 2% experienced prolonged 
bacteremia, and 6% died from unknown causes. These 
findings highlight the complexity of  GNB management 
and the need for comprehensive strategies to prevent 
adverse events.

Salmonella Typhi 33 (16.67%) 5 (3.13%)  
Serratia 5 (2.53%) 6 (3.75%)  
Unidentified anaerobic Bacilli 0 (0.00%) 1 (0.63%)  
Pseudomonas 1 (0.51%) 0 (0.00%)  
Stenotrophomonas 0 (0.00%) 1 (0.63%)  
Missing 6 (3.03%) 8 (5.00%)  
Resistance   0.49
ESBL 57 (28.93%) 46 (28.75%)  
MDR 9 (4.57%) 12 (7.50%)  
None 131 (66.50%) 102 (63.75%)  
Source bacteremia (Fisher's exact)   0.004
Urinary tract infection 71 (36.04%) 71 (44.38%)  
Bone and soft tissue infection 7 (3.55%) 15 (9.38%)  
Burn wound infection 3 (1.52%) 0 (0.00%)  
Cardiovascular infection 1 (0.51%) 2 (1.25%)  
intra-abdominal infection 70 (35.53%) 31 (19.38%)  
Line related infection 4 (2.03%) 7 (4.38%)  
Lower respiratory tract infection 20 (10.15%) 17 (10.63%)  
Unknown 20 (10.15%) 17 (10.63%)  
Surgical site infection 1 (0.51%) 0 (0.00%)  

Figure 1: The primary clinical outcomes of  this study are shown in chart

The duration of  treatment with intravenous antibiotics 
revealed that most patients underwent a short course 
of  intravenous therapy. Specifically, more than 70% of  
patients received treatment lasting less than 10 days, 

which suggests a trend towards shorter intravenous 
antibiotic therapy durations in managing gram-negative 
bacteremia cases, as shown in Table 2.



Pa
ge

 
95

https://journals.e-palli.com/home/index.php/ajmsi

Am. J. Med. Sci. Innov. 3(2) 91-102, 2024

Table 2: Intravenous (IV) treatment duration – intervals
Duration of  IV treatment (days) Counts Percentages %
<7 161 44.97
7 to 10 100 27.93
11 to 14 54 15.08
>14 43 12.01
Sum 358 100

Figure 2 shows the distribution of  gram-negative 
bacteremia by infection site. Urinary tract infections 
are most common (45%), followed by intra-abdominal 
infections (40%) and lower respiratory tract infections 
(15%). A notable proportion (10%) has an unknown 
infection site. Other sites include bone and soft 

tissue infections (5%), line-related infections (2.5%), 
cardiovascular infections (1%), and miscellaneous 
sources (2.5%). This breakdown underscores the varied 
origins of  gram-negative bacteremia, emphasising the 
need for tailored treatment strategies based on infection 
site specificity.

Figure 2: Epidemiology of  gram-negative bacteremia

Escherichia coli was the most frequently identified 
organism, accounting for 47.2% of  cases, followed by 
Klebsiella pneumoniae (16.4%), Salmonella enterica 
serotype Typhi (10.6%), and Pseudomonas aeruginosa 
(7.8%). Other less common organisms included Serratia 
marcescens (3%), Acinetobacter baumannii (2.2%), 
Brucella sp. (2.2%), non-typhoidal Salmonella (1.3%), 
Citrobacter sp. (0.5%), and various others (8.3%). These 

findings detail the characteristics of  gram-negative 
bacteria isolated in the study, highlighting the prevalence 
of  different species contributing to persistent bacteremia 
cases. Additionally, the mean duration of  antimicrobial 
treatment, including intravenous and oral administration, 
was 14.6 days, with intravenous antibiotics specifically 
administered for an average duration of  5.4 days, as 
shown in Table 3.

Table 3: Organisms isolated in persistent bacteremia
Organism Count (out of  18) Percentage %
E. coli 4 22.22
Klebsiella sp. 5 27.77
Enterobacter cloacae 1 5.55
Pseudomonas sp. 2 11.11
Salmonella typhi 3 16.66
Proteus sp. 1 5.55
Stenotrophomonas maltophilia 1 5.55
Achromobacter sp. 1 5.55

As illustrated in Figure 3, gram-negative bacteremia arises 
from various sources within the body. The most prevalent 
infection sites of  cases originating in the urinary tract are 
evident. Intra-abdominal infections and lower respiratory 

tract infections follow this. It is crucial to note that these 
percentages may not match the original figure exactly due 
to potential rounding errors.



Pa
ge

 
96

https://journals.e-palli.com/home/index.php/ajmsi

Am. J. Med. Sci. Innov. 3(2) 91-102, 2024

There were four cases of  multidrug-resistant organisms 
(MDROs), two Klebsiella pneumoniae carbapenemase-
producing Enterobacteriaceae (KPC), and two New 
Delhi metallo-beta-lactamase-1 (NMD-1). Extended-
spectrum beta-lactamase-producing organisms (ESBL) 
constituted 31.56% (113) cases. Antibiotic collateral 
damage was noted as the emergence of  MDRO in 90 days 
in 22 patients (6.1%) and Clostridium difficile in two patients 

(0.5%). Persistent bacteremia was reported in 18 patients 
(5%), out of  which nine (50%) had intra-abdominal 
infections, three had soft tissue infections (16.7%), two 
had lower respiratory tract infections (11.1%), two had 
urinary tract infections (11.1%), one had cardiovascular 
infection (5.5%), and one had line-related infection 
(5.5%), as shown in Table 4.

Figure 3: Common sites of  infection in gram-negative bacteremia cases

Table 4: Description of  bacterial isolates
Organisms Count Percentage (%)
Multidrug-resistant organisms (MDROs) 4 1.11
Extended-spectrum beta-lactamase-producing organisms (ESBL) 113 31.56
Sensitive strains 241 67.32
Single microbe 336 93.85
Polymicrobial 22 6.14

Figure 4 illustrates the distribution of  gram-negative 
bacteremia cases by different bacterial types. The listed 
bacteria include Escherichia coli, Klebsiella pneumoniae, 
Salmonella typhi, Pseudomonas, Serratia, Acinetobacter, 
non-typhoidal Salmonella, and Citrobacter. The X-axis 

represents the percentage of  cases for each bacterial type. 
This graph provides insights into the prevalence of  various 
bacterial species causing gram-negative bacteremia, which 
is essential for understanding the epidemiology and guiding 
treatment approaches for these infections.

Figure 4: Comorbidities in gram-negative bacteremia cases



Pa
ge

 
97

https://journals.e-palli.com/home/index.php/ajmsi

Am. J. Med. Sci. Innov. 3(2) 91-102, 2024

Table 5 illustrates the management of  source control in 
patients with persistent bacteremia. Among 18 patients 
with persistent bacteremia, source control was performed 
in seven cases, accounting for 38.9% of  the cohort. 

Conversely, five patients (27.8%) did not require source 
control. In contrast, source control was deemed necessary 
in six cases (33.3%) but was not carried out due to factors 
such as the patient’s unstable condition or inaccessible sites.

Table 5: Comorbidities of  Study Population
Comorbidity Number Percentage (%)
Diabetes mellitus 160 44.69
Hypertension 152 42.45
The end-stage renal disease of  dialysis 32 8.93
Chronic kidney disease 44 12.29
Malignancy 36 10.05
Asthma/Chronic Obstructive Pulmonary Disease 24 6.70
Human Immunodeficiency Virus 1 0.27
Ischemic heart disease 45 12.56
Heart failure 23 6.42
Chronic liver disease 22 6.14
Pregnancy 8 2.23
Valvular disease 13 3.63
Cystic fibrosis 0 0
Inflammatory bowel disease 1 0.27
Tuberculosis 1 0.27
Immunosuppressive treatment 24 6.70

Figure 5 presents the survival probability comparison 
between diabetic and nOn-diabetic patients following 
a positive culture. According to the graph, patients 
without diabetes have a better chance of  surviving than 
those with the disease. This observation underscores 
the potential impact of  diabetes as a comorbidity on 

patient outcomes in cases of  gram-negative bacteremia. 
Understanding such differences in survival probabilities 
can inform clinical decision-making and highlight the 
importance of  tailored management strategies for 
patients with diabetes who develop gram-negative 
bacteremia.

Figure 5: Kaplan-Meier survival analysis denoting survival probability of  diabetic and non-diabetic groups

Table 6 presents the duration of  antibiotic treatment 
in diabetic (DM) and non-diabetic (non-DM) patient 
groups with gram-negative bacteremia. Statistical analysis 
revealed no significant difference in the duration of  

antibiotic treatment between the two groups (p=0.617). 
Most patients in both groups received antibiotics for 
more than 14 days, with 63 (31.98%) in the DM group 
and 52 (32.5%) in the non-DM group. Interestingly, a 



Pa
ge

 
98

https://journals.e-palli.com/home/index.php/ajmsi

Am. J. Med. Sci. Innov. 3(2) 91-102, 2024

slightly higher percentage of  diabetic patients (10.63%) 
received antibiotics for less than 7 days compared to 
non-diabetic patients (8.63%). Moreover, a somewhat 

higher proportion of  diabetic patients (35.63%) received 
antibiotics for 11 to 14 days compared to non-diabetic 
patients (32.49%).

Table 6: Total duration of  antibiotic treatment in diabetic and non-diabetic patients
Total duration of  treatment (days) Non-DM (n=197) DM  (n=160)

Count Percentages % Count Percentages %
Less than 7 days 17   8.63 17 10.63
7 to 10 days 53 26.90 34  21.25
11 to 14 days 64 32.49 57 35.63
More than 14 days 63 31.98 52 32.5

P-value = 0.617

Univariate analysis of  recurrence at 90 days, cure rate, 
and death due to sepsis showed a significant difference 
between the groups (p=0.037, p=0.09, p=0.052, 
respectively. The sepsis outcomes comparison revealed 
that diabetic patients had a higher death risk due to 

sepsis (11.88%) and recurrence within 90 days (8.75%) 
compared to non-diabetic patients. Additionally, the cure 
rate is less (69.38%) in diabetic patients than in non-
diabetic patients (81.73%), as shown in Table 7.

Table 7: Univariate analysis of  outcomes in diabetic and non-diabetic patients
Outcome (Fisher's exact) Non-DM (n=197) DM (n=160) P-value
Death due to sepsis 11 (5.58%) 19 (11.88%) 0.052 
Recurrence in 90 days 7 (3.55%) 14 (8.75%) 0.037 
Cured 161 (81.73%) 111 (69.38%)  0.009

Age, treatment duration of  fewer than seven days, 
and hospital-acquired infections showed a significant 
association with higher mortality in gram-negative 
bacteremia in the multivariate analysis (OR=1.040, 
p=0.014), (OR=20.030, p=0.001), (OR=3.517, p=0.020) 
respectively. Conversely, the presence of  E. coli and UTI 

as sources of  infection was not significantly associated 
with mortality due to sepsis. Kaplan-Meier survival 
analysis was used to assess the survival probability of  the 
diabetic and non-diabetic groups. The log-rank test result 
was insignificant (p=0.934), as shown in Table 8.

Table 8: Multivariate analysis of  factors associated with mortality in gram-negative bacteremia patients adjusting for 
baseline characteristics
Variable OR p-value 95% Confidence Interval
Age 1.040 0.014 1.008 1.072
Male 1.609 0.448 0.471 5.496
DM 1.008 0.990 0.314 5.496
HTN 4.060 0.056 0.967 17.049
ESRD/HD 1.237 0.756 0.324 4.716
Less than 7 days of  treatment 20.030 <0.001 5.454 75.038
Hospital-acquired 3.517 0.020 1.217 10.168
Secondary 1.394 0.559 0.457 4.253
MDR 0.588 0.547 0.104 3.309
E. coli 0.457 0.192 0.141 1.482
UTI - a source of  infection 0.043 0.007 0.004 0.040

Discussion
GNB bloodstream infections pose a serious health 
problem globally and in the Middle East, where 
antimicrobial resistance is rising (Inam et al., 2023). 
Several studies have been conducted in this region to 
understand this condition’s epidemiology and risk factors. 

The emergence of  antimicrobial resistance (AMR) has 
been the top agenda item for the past four years for 
the Gulf  Cooperation Council Centre for Infection 
Control (GCC-IC) (Al Muhairi et al., 2019). A previous 
study on the epidemiology of  all bacteremia patients in 
Qatar found 452 cases of  bacteremia with 63% gram-



Pa
ge

 
99

https://journals.e-palli.com/home/index.php/ajmsi

Am. J. Med. Sci. Innov. 3(2) 91-102, 2024

negative organisms (Borgio et al., 2021), with Escherichia 
coli as the most common isolate. The present study also 
found E. coli to be the predominant bacterium (47.2%), 
followed by Klebsiella pneumoniae (16.4%). Many cases 
of  Salmonella bloodstream infections (10.6%) in our 
centre were identified mainly as travellers or immigrants 
from Southeast Asia. Salmonella typhi was 10.6%, and 
non-typhoidal Salmonella constituted 1.3% of  cases. 
An earlier study by Qatar found that 97% of  patients 
had a history of  travel to endemic areas (Ahmedullah 
et al., 2018). Salmonella typhi isolates from the present 
study centre demonstrated high levels of  resistance to 
ciprofloxacin (40%) but were susceptible to ceftriaxone. 
Among the cases, the Brucella sp. was identified in eight 
patients (2.2 %). In the Middle East and North Africa 
(MENA) region, brucellosis is not uncommon as a blood 
culture isolate (Wareth et al., 2022). Usually, there is a 
history of  exposure to cattle and camels, either through 
occupational exposure or consumption of  dairy products.
MDROs and ESBL-producing isolates comprised 34% 
of  the samples, while the rest were sensitive strains 
(66%). Previous studies also found a higher prevalence 
of  ESBL-producing E. coli and Klebsiella pneumoniae 
(55.7%) than present findings (Sid Ahmed et al., 2023), 
which indicates the implementation of  antimicrobial 
stewardship practices and monitoring the appropriateness 
of  antimicrobials and their consumption. In addition, 
previous studies from Qatar reported 4.4 % MDR 
isolates of  Pseudomonas aeruginosa (P. aeruginosa)  (Ahmed 
et al., 2019); however, out of  28 patients with P. aeruginosa 
bloodstream infection (7.8%), only 2 patients (0.56%) 
were multidrug-resistant, which is in contrast to studies 
from Saudi Arabia with a high prevalence of  multidrug-
resistant (MDR) bacteria, with more than 50% of  the 
isolates resistant to at least one antimicrobial agent (Yezli 
et al., 2014). Although P. aeruginosa remains susceptible to 
carbapenems, quinolones, and aminoglycosides in most 
centres in Saudi Arabia, its resistance is still on the rise. 
Similarly, Enterobacteriaceae, Escherichia coli, Klebsiella 
pneumoniae, and Enterobacter sp. AMR is increasing, 
especially in gram-negative infections in the Middle East 
(Sid Ahmed et al., 2023). Prior use of  antimicrobials is an 
established independent risk factor for the emergence of  
MDROs (Ahmed et al., 2019). In Qatar, about half  of  the 
cases of  Klebsiella pneumonia are reported as extended-
spectrum β-lactamase (ESBL) producers (Alsamawi 
et al., 2022). A survey from Oman found Escherichia coli 
(32.39%), P.aeroginosa  (22.16%),  Klebsiella pneumoniae 
(19.97%), and Acinetobacter baumannii (5.22%), with 
growing resistance against ciprofloxacin and meropenem 
(Sathya Kumar et al., 2023). The factors included 
prolonged hospital stay, intravenous cannulation, multiple 
co-morbid conditions, and previous antibiotic exposure, 
which are attributed to the resistance in the present study.
A study in Iran demonstrated that the most common 
gram-negative infections included Klebsiella pneumoniae, 
Escherichia coli, Serratia marcescens, and Pseudomonas 
aeruginosa (Mahmoudi et al., 2023). The study also found 

a high prevalence of  carbapenem-resistant isolates, 
with more than 70% Klebsiella pneumoniae carbapenem-
resistant; therefore, the implementation of  antimicrobial 
stewardship and infection prevention measures is 
necessary to control the emergence and subsequent 
spread of  AMR, as they are two facets of  the same coin. 
In Sub-Saharan Africa, the levels of  third-generation 
cephalosporins resistance in the bloodstream are 
reported to be high in Escherichia coli (18.4%), Klebsiella 
sp. (54.4%), non-typhoidal Salmonellae (1.9% ) (Lester et 
al., 2020). Studies from Finland, Australia, Sweden, and 
Canada have shown increased overall resistant Escherichia 
coli BSI rates (Buetti et al., 2017). Persistent bacteremia 
was reported in 18 patients (5 %), with the most common 
pathogens being Klebsiella sp. and Escherichia coli. Source 
control was performed in only one-third of  the patients; 
out of  30 patients, 13 (43.3%) have died due to persistent 
bacteremia; source control was performed for eight of  
them.
Persistent bacteremia is a serious condition that can lead 
to significant morbidity and mortality and increased 
healthcare costs (Iskandar et al., 2021).  The epidemiology 
of  persistent GNB is complex and is influenced 
by factors such as prior antibiotic use, exposure to 
healthcare facilities, and comorbidities. Several studies 
have identified risk factors such as end-stage renal disease 
(ESRD) during hemodialysis, intravascular devices, 
bacteremia due to MDRO organisms, and ineffective 
antibiotic therapy as independent predictors of  persistent 
GNB bacteremia (De Waele et al., 2018). The incidence of  
persistent GNB is increasing, with higher rates observed 
in older adults and patients with comorbidities (De Waele 
et al., 2018). Persistent GNBs are often seen in patients 
with weakened immune systems, such as malignancies, 
HIV, or organ transplants (Tumbarello et al., 2012). The 
main contributing factors to GNB bacteremia were DM-
2, hypertension, ischemic heart disease, and chronic 
kidney disease in the present study. Approximately 
10% of  patients had malignancy, and 6.7% were on 
immunosuppressive drugs. 
The management of  persistent bacteremia can be 
challenging and requires a multidisciplinary approach. 
The first step in management includes identifying the 
source of  the infection. Appropriate antimicrobial therapy 
should be initiated with proper source control, including 
removing infected intravascular devices, such as central 
venous catheters, or surgical intervention to remove 
infected tissue. A reasonable approach for source control 
was observed in the patient population. Fortunately, there 
were only a handful of  cases where it was indicated but 
not performed. Appropriate antibiotic therapy should 
be used based on the organism’s susceptibility pattern to 
manage persistent GNB effectively. Chu et al. found that 
inappropriate initial antimicrobial treatment increases 
mortality risk (Chu et al., 2020). All GNB bacteremia 
in patients are reported directly to the infectious 
disease physician on call by the Clinical Microbiology 
Department as a part of  the antimicrobial stewardship 



Pa
ge

 
10

0

https://journals.e-palli.com/home/index.php/ajmsi

Am. J. Med. Sci. Innov. 3(2) 91-102, 2024

program. As part of  the same stewardship, broad-
spectrum antimicrobials are authorised by infectious 
disease physicians within 48 hours of  initiation. A 
combination therapy may be necessary to achieve 
adequate bacterial clearance (Kalelkar et al., 2022); the 
empirical antimicrobials were started according to study 
hospital guidelines and subsequently tailored to narrow-
spectrum agents as soon as sensitivities were available.
Local epidemiology of  infective organisms, antibiograms, 
immune status, previous antimicrobial exposure, possible 
source of  infection, and colonisation with MDR bacteria 
and other alert microorganisms such as Clostridium difficile 
and Candida auris must be considered before initiating 
empirical therapy. Initial broad-spectrum antibiotics 
should be administered empirically in severely ill patients, 
followed by source identification and control as soon as 
possible (Timsit et al., 2020). De-escalation from a broad-
spectrum to a narrow-spectrum antimicrobial when 
culture and sensitivity results are available effectively 
reduces AMR (Lester et al., 2020) and is rigorously 
followed in our hospital. On average, the duration of  
Intravenous (IV) antibiotics was 5-8 days, although 
longer durations were used when the underlying illness 
and source of  infection were present. Another important 
intervention was the close teamwork relationship and 
clinical discussions between our infectious disease 
physicians and medical microbiologists in decision-
making (De Waele et al., 2018).
In South Korea, extended-spectrum beta-lactamase-
producing Enterobacterales have emerged as a significant 
cause of  community-acquired bacteremia after the prior 
use of  antimicrobials (Timsit et al., 2020). The present 
study did not look for previous use of  antimicrobials 
but noted that last hospitalisation and prolonged 
hospital stay were associated with a higher emergence of  
resistance. Similarly, a study from Lebanon reported that 
infections caused by resistant bacteria were associated 
with a significant increase in hospital stays compared to 
those with susceptible bacteria, leading to higher costs 
(Iskandar et al., 2021). The duration of  antibiotic therapy 
for gram-negative bacteremia depends on several factors, 
such as the site of  infection, severity of  illness, and the 
type of  causative organism. In this study, many patients 
received IV antibiotics for less than 7 days, while only 
12% received treatment for more than 14 days (either 
due to persistent bacteremia or complicated bacteremia). 
Several studies have determined the optimal duration of  
antibiotic therapy for gram-negative bacteremia  (Dyer et 
al., 2019; Lee et al., 2019). Yahav et al. found that a short 
course of  antibiotic therapy (7 days) was as effective as a 
longer course (14 days) in the treatment of  gram-negative 
bacteremia (Yahav et al., 2019). A meta-analysis of  three 
randomised controlled trials (RCTs) with 1121 patients 
with Enterobacterale bacteremia showed no significant 
difference in 90 days of  mortality between 7 and 14 days 
of  treatment (Turjeman et al., 2023). 
Shorter durations of  antimicrobials are advocated as 
a goal for many antimicrobial stewardship programs 

to treat community-acquired pneumonia, urinary tract 
infections, intra-abdominal infections, and skin and soft-
tissue infections. Batlas et al. reported an overall mortality 
at 1 year of  36.2 %, with 18% within the first 30 days 
(Baltas et al., 2021). Similarly, a study from Calgary found 
that 28-day, 90-day, and 365-day all-cause case-fatality 
rates after bloodstream infection were 12%, 17%, and 
25%, respectively (Laupland et al., 2011). A study by 
Qatar showed a hospital mortality rate of  29.7 % for 
all bacteremia cases (Khan et al., 2010). A larger study 
examined the epidemiology of  bloodstream infections 
in 51 countries across six continents in critically ill 
patients, including COVID-19 patients (Buetti et al., 
2017), found that gram-negative bacteria were the most 
common cause of  bloodstream infections and the overall 
mortality for bloodstream infections was 45%, with 
higher rates reported in Covid-19 patients (Buetti et al., 
2017). Mortality due to gram-negative bacteremia can 
vary depending on various factors, such as the specific 
bacterial species involved, age and overall health of  the 
patient, presence of  underlying medical conditions, and 
promptness and effectiveness of  treatment. The mortality 
from gram-negative bacteremia is higher than that from 
gram-positive bacteremia, with some studies suggesting 
mortality ranging between 20 and 50%. However, mortality 
rates can vary widely based on individual circumstances, 
and it is important to note that timely and appropriate 
antibiotic treatment can greatly improve outcomes in 
patients with gram-negative bacteremia. The incidence 
and mortality rates of  gram-negative bacteremia can vary 
globally, depending on healthcare practices, antibiotic 
resistance patterns, and population demographics. The 
study centre has an antimicrobial stewardship program 
with formulary restriction and preauthorisation of  
restricted antimicrobials that aid in appropriately starting 
antimicrobials, particularly in bacteremia cases, and is 
followed by the infectious disease team in collaboration 
with the medical microbiologist, which could be one 
reason why the MDRO rate was not significantly high. 
However, cephalosporins are not restricted in clinical 
practice, which might explain the higher numbers of  
ESBL-producing Enterobacterales.

CONCLUSION
In conclusion, gram-negative BSIs are serious infections 
with increasing antimicrobial resistance (AMR). Extended-
spectrum beta-lactamase (ESBL) producing bacteria are 
our centre’s most common cause of  AMR. Diabetes 
Mellitus-2, old age and hospital-acquired infections 
are risk factors leading to higher mortality. Healthcare 
professionals should be aware of  the risk factors 
associated with this condition and initiate empirically 
effective antibiotic therapy to achieve optimal treatment 
outcomes and prevent collateral damage. Further research 
is needed to understand better the epidemiology and 
pathophysiology of  gram-negative bacteremia in Qatar 
and formulate effective targeted treatment strategies.



Pa
ge

 
10

1

https://journals.e-palli.com/home/index.php/ajmsi

Am. J. Med. Sci. Innov. 3(2) 91-102, 2024

LIMITATIONS
The limitations of  our study include the need for more 
data on the prior use of  antimicrobials and health care 
costs. The long-term impact of  GNB beyond 3 months 
has yet to be investigated. The retrospective nature of  
this study and the single-center data are other limitations. 
Further analysis with a larger sample size is recommended 
to enhance the understanding of  these findings in clinical 
practice. In this study, we only looked at long-term 
mortality within 90 days. Still, collateral damage was 
determined, such as the emergence of  MDRO in 90 days 
at 6.1%, while infection with Clostridioides difficile occurred 
only in 2 patients (0.5%).

Acknowledgement
Clinical Microbiology Department and Pharmacy 
Department 

Data Availability Statement
The data used to support the findings of  this study 
were restricted by the Institutional Review Board (IRB) 
medical research centre at Hamad Medical Corporation 
to protect patients’ privacy. Data can be obtained after 
IRB approval for researchers who meet the criteria for 
access to confidential data.

REFERENCES 
Ahmed, M. S., Hassan, A., Jarir, S. A., Hadi, H. A., Bansal, 

D., Wahab, A. A., Muneer, M., Mohamed, S., Zahraldin, 
K., & Hamid, J. (2019). Emergence of  multidrug-and 
pandrug-resistant Pseudomonas aeruginosa from five 
hospitals in Qatar. Infection Prevention in Practice, 1(3-4), 
100027. 

Ahmedullah, H., Khan, F. Y., Al Maslamani, M., Al 
Soub, H., Chacko, K., Khattab, M. A., Mahmoud, S., 
Howaidy, F., Thapur, M., & Al Madhoun, E. (2018). 
Epidemiological and clinical Features of  Salmonella 
Typhi infection among adult patients in Qatar: a 
hospital-based study. Oman medical journal, 33(6), 468. 

Al Muhairi, F. M., Bulshawareb, A. M., Al Nuaimi, A. M., 
Al Hemeiri, M. K., Al Aiyan, A., & Mohteshamuddin, 
K. (2019). The role of  antimicrobials in food animals 
in the emergence of  resistant human pathogens. 
International Journal of  Medical Reviews and Case Reports, 
3(9), 598-608. 

Alsamawi, M., Joudeh, A. I., Eldeeb, Y., Al-Dahshan, A., 
Khan, F., Ghadban, W., Almaslamani, M., & Alkhal, 
A. (2022). Epidemiology of  extended-spectrum beta-
lactamase producing Enterobacteriaceae in Qatar: A 
3-year hospital-based study. Frontiers in Antibiotics, 1, 
980686. 

Baltas, I., Stockdale, T., Tausan, M., Kashif, A., Anwar, J., 
Anvar, J., Koutoumanou, E., Sidebottom, D., Garcia-
Arias, V., & Wright, M. (2021). Long-term outcome 
and risk factors for late mortality in Gram-negative 
bacteraemia: a retrospective cohort study. Journal of  
global antimicrobial resistance, 25, 187-192. 

Bassetti, M., Rello, J., Blasi, F., Goossens, H., Sotgiu, G., 

Tavoschi, L., Zasowski, E. J., Arber, M. R., McCool, 
R., & Patterson, J. V. (2020). Systematic review of  
the impact of  appropriate versus inappropriate initial 
antibiotic therapy on outcomes of  patients with severe 
bacterial infections. International journal of  antimicrobial 
agents, 56(6), 106184. 

Borgio, J. F., Rasdan, A. S., Sonbol, B., Alhamid, G., 
Almandil, N. B., & AbdulAzeez, S. (2021). Emerging 
status of  multidrug-resistant bacteria and fungi in the 
arabian peninsula. Biology, 10(11), 1144. 

Buetti, N., Atkinson, A., Kronenberg, A., Marschall, J., 
& Schrenzel, J. (2017). Different epidemiology of  
hospital-acquired bloodstream infections between 
small community hospitals and large community 
hospitals. Clinical Infectious Diseases, 64(7), 984–985. 

Chu, S.-M., Hsu, J.-F., Lai, M.-Y., Huang, H.-R., Chiang, 
M.-C., Fu, R.-H., & Tsai, M.-H. (2020). Risk factors 
of  initial inappropriate antibiotic therapy and the 
impacts on outcomes of  neonates with gram-negative 
bacteremia. Antibiotics, 9(4), 203. 

De Waele, J. J., Akova, M., Antonelli, M., Canton, R., 
Carlet, J., De Backer, D., Dimopoulos, G., Garnacho-
Montero, J., Kesecioglu, J., & Lipman, J. (2018). 
Antimicrobial resistance and antibiotic stewardship 
programs in the ICU: insistence and persistence in 
the fight against resistance. A position statement 
from ESICM/ESCMID/WAAAR round table on 
multidrug resistance. Intensive care medicine, 44, 189-196. 

Dyer, A. P., Ashley, E. D., Anderson, D. J., Sarubbi, C., 
Wrenn, R., Hicks, L. A., Srinivasan, A., & Moehring, 
R. W. (2019). Total duration of  antimicrobial therapy 
resulting from in-patient hospitalisation. Infection 
Control & Hospital Epidemiology, 40(8), 847-854. 

Fitzpatrick, J., Biswas, J., Edgeworth, J., Islam, J., Jenkins, 
N., Judge, R., Lavery, A., Melzer, M., Morris-Jones, 
S., & Nsutebu, E. (2016). Gram-negative bacteraemia; 
a multi-centre prospective evaluation of  empiric 
antibiotic therapy and outcome in English acute 
hospitals. Clinical Microbiology and Infection, 22(3), 244-
251. 

Gajdács, M., Burián, K., & Terhes, G. (2019). Resistance 
levels and epidemiology of  non-fermenting gram-
negative bacteria in urinary tract infections of  in-
patients and outpatients (RENFUTI): a 10-year 
epidemiological snapshot. Antibiotics, 8(3), 143. 

Inam, S., Ikram, S., Malik, I. Y., Jabeen, K., & Saeed, M. 
T. (2023). Current trends in blood stream infections: 
Pathogens and their antimicrobial susceptibility 
pattern. Pakistan Postgraduate Medical Journal, 34(02), 
83–87.

Iskandar, K., Roques, C., Hallit, S., Husni-Samaha, 
R., Dirani, N., Rizk, R., Abdo, R., Yared, Y., Matta, 
M., & Mostafa, I. (2021). The healthcare costs of  
antimicrobial resistance in Lebanon: a multi-centre 
prospective cohort study from the payer perspective. 
BMC Infectious Diseases, 21(1), 404. 

Kalelkar, P. P., Riddick, M., & García, A. J. (2022). 
Biomaterial-based antimicrobial therapies for the 



Pa
ge

 
10

2

https://journals.e-palli.com/home/index.php/ajmsi

Am. J. Med. Sci. Innov. 3(2) 91-102, 2024

treatment of  bacterial infections. Nature Reviews 
Materials, 7(1), 39-54. 

Khan, F. Y., Elshafie, S. S., Almaslamani, M., Abu-Khattab, 
M., El Hiday, A. H., Errayes, M., & Almaslamani, 
E. (2010). Epidemiology of  bacteraemia in Hamad 
general hospital, Qatar: a one year hospital-based 
study. Travel medicine and infectious disease, 8(6), 377-387. 

Kim, Y. A., & Park, Y. S. (2018). Epidemiology and 
treatment of  antimicrobialresistant gram-negative 
bacteria in Korea. The Korean journal of  internal medicine, 
33(2), 247. 

Kitaya, S., Kanamori, H., Katori, Y., & Tokuda, K. 
(2023). Impact of  Persistent Multidrug-Resistant 
Gram-Negative Bacteremia on Clinical Outcome and 
Mortality. Antibiotics, 12(2), 313. 

Kwiecińska-Piróg, J., Skowron, K., & Gospodarek-
Komkowska, E. (2018). Primary and Secondary 
Bacteremia Caused by spp.: Epidemiology, Strains 
Susceptibility and Biofilm Formation. Polish journal of  
microbiology, 67(4), 471-478. 

Laupland, K., Svenson, L., Gregson, D., & Church, 
D. (2011). Long-term mortality associated with 
community-onset bloodstream infection. Infection, 39, 
405-410. 

Lee, C.-C., Hsieh, C.-C., Yang, C.-Y., Hong, M.-Y., Lee, 
C.-H., Tang, H.-J., & Ko, W.-C. (2019). Short versus 
long duration antimicrobial treatment for community-
onset bacteraemia: A propensity score matching study. 
International journal of  antimicrobial agents, 54(2), 176-183. 

Lester, R., Musicha, P., Van Ginneken, N., Dramowski, 
A., Hamer, D. H., Garner, P., & Feasey, N. A. 
(2020). Prevalence and outcome of  bloodstream 
infections due to third-generation cephalosporin-
resistant Enterobacteriaceae in sub-Saharan Africa: a 
systematic review. Journal of  Antimicrobial Chemotherapy, 
75(3), 492-507. 

Mahmoudi, S., Pourakbari, B., Rostamyan, M., Raji, H., 
Sadeghi, R. H., & Mamishi, S. (2023). Antimicrobial 
Resistance Patterns of  Gram-negative Bacteria in an 
Iranian Referral Pediatric Hospital: A Present Danger 
of  New Delhi Metallo-β-lactamase. Infectious Disorders-
Drug Targets (Formerly Current Drug Targets-Infectious 
Disorders), 23(6), 7-14. 

Sathya Kumar, A. M., George, M. M., Bhanuprasad, K., 
John, G. M., Korula, A., Abraham, A., Mathews, V., 
Kulkarni, U. P., Shankar, C., & Premkumar, P. S. (2023). 
Persistent bacteremia predicts poor outcomes among 
neutropenic patients with carbapenem-resistant 
gram-negative bloodstream infections receiving 

appropriate therapy. Annals of  Clinical Microbiology and 
Antimicrobials, 22(1), 12. 

Sid Ahmed, M. A., Petkar, H. M., Saleh, T. M., Albirair, 
M., Arisgado, L. A., Eltayeb, F. K., Mahmoud Hamed, 
M., Al-Maslamani, M. A., Al Khal, A. L., & Alsoub, 
H. (2023). The epidemiology and microbiological 
characteristics of  infections caused by Gram-negative 
bacteria in Qatar: national surveillance from the Study 
for Monitoring of  Antimicrobial Resistance Trends 
(SMART): 2017 to 2019. JAC-Antimicrobial Resistance, 
5(4), dlad086. 

Spellberg, B., & Rice, L. B. (2019). Duration of  antibiotic 
therapy: shorter is better. Annals of  internal medicine, 
171(3), 210-211. 

Timsit, J.-F., Ruppé, E., Barbier, F., Tabah, A., & Bassetti, 
M. (2020). Bloodstream infections in critically ill 
patients: an expert statement. Intensive care medicine, 46, 
266-284. 

Tumbarello, M., Viale, P., Viscoli, C., Trecarichi, E. M., 
Tumietto, F., Marchese, A., Spanu, T., Ambretti, 
S., Ginocchio, F., & Cristini, F. (2012). Predictors 
of  mortality in bloodstream infections caused by 
Klebsiella pneumoniae carbapenemase–producing 
K. pneumoniae: importance of  combination therapy. 
Clinical Infectious Diseases, 55(7), 943-950. 

Turjeman, A., von Dach, E., Molina, J., Franceschini, E., 
Koppel, F., Yelin, D., Dishon-Benattar, Y., Mussini, C., 
Rodríguez-Baño, J., & Cisneros, J. M. (2023). Duration 
of  antibiotic treatment for Gram-negative bacteremia: 
Systematic review and individual participant data 
(IPD) meta-analysis. EClinicalMedicine, 55, 101755. 

Wareth, G., Dadar, M., Ali, H., Hamdy, M. E., Al‐Talhy, 
A. M., Elkharsawi, A. R., Tawab, A. A. A. E., & 
Neubauer, H. (2022). The perspective of  antibiotic 
therapeutic challenges of  brucellosis in the Middle 
East and North African countries: Current situation 
and therapeutic management. Transboundary and 
Emerging Diseases, 69(5), e1253-e1268. 

Yahav, D., Franceschini, E., Koppel, F., Turjeman, 
A., Babich, T., Bitterman, R., Neuberger, A., 
Ghanem-Zoubi, N., Santoro, A., & Eliakim-Raz, N. 
(2019). Seven versus 14 days of  antibiotic therapy 
for uncomplicated gram-negative bacteremia: a 
noninferiority randomised controlled trial. Clinical 
Infectious Diseases, 69(7), 1091-1098. 

Yezli, S., Shibl, A. M., Livermore, D. M., & Memish, Z. 
A. (2014). Prevalence and antimicrobial resistance 
among Gram-negative pathogens in Saudi Arabia. 
Journal of  chemotherapy, 26(5), 257-272.


