الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
AML is a cancer of blood and bone marrow. It is the most common form of acute leukemia, with an incidence that increases with advanced age. Although it is usually of unknown etiology, it can also develop following exposure to genotoxic agents or following an antecedent hematologic disorder (e.g., marrow failure syndrome). FN is a serious complication of cancer chemotherapy that can lead to delay in treatment and necessary dose reductions of chemotherapy, which compromise treatment efficacy.
Infections are an important cause of morbidity and mortality in leukemic patients with FN. Over the past decade, there has been a considerable change in the spectrum and antibiotic susceptibility patterns of pathogens causing infections in patients with FN. The most effective empirical antimicrobial regimen must be rapidly administered to febrile neutropenic patients as delay in the initiation of treatment may result in septicemic shock and thus increase mortality. Cefepime is the antibiotic of choice for most FN episodes in hematology departments. It has been claimed that some risk factors were independently associated with cefepime-resistance.
This work aimed to study the bacteriological profile of FN among acute myeloid leukemic patients, risk factors predicting bacterial resistance to empirically used cefepime in hematology wards and to compute an easy to use scoring system for predicting cefepime resistance.
The present cross-sectional study was conducted over a period of thirteen months from October 2017 to October 2018. It enrolled 170 adult AML patients with FN who were admitted in the Hematology Department (hematology wards) at the AMUH.
A questionnaire sheet was filled in for each patient enrolled in this study, including all the relevant information as age, sex, past medical history, time elapsed since diagnosed with AML, phase of therapy and presence of abnormal laboratory results. Another questionnaire sheet included the risk factors predicting cefepime resistance such as surgery, admission to ICU, neutrophil count, time elapsed since hospital admission, CVC, urinary catheter, severe mucositis, antibiotic therapy with β-lactams was completed for each patient included in the study.
A total of 200 clinical samples were collected from the 170 studied patients, distributed as 170 blood samples and 30 pus and exudate samples. These samples were collected upon request of the treating physician or whenever needed. All collected samples were transported to the Microbiology Laboratory at the HIPH as soon as possible for processing. Blood culture bottles were incubated at 37oC for 24 hours. Collected clinical samples were cultured on blood and MacConkey’s agar plates and incubated aerobically at 37oC for 24 hours. Isolates were identified according to the standard microbiological methods. All bacterial isolates were tested for their antibiotic susceptibility patterns by disc diffusion method according to the CLSI recommendations. Data were analyzed using the appropriate statistical techniques and an easy to use scoring system was built and computed.
The results of this study can be summarized as follows:
1- Of the 170 examined febrile neutropenic AML patients, 110 (64.7%) were males and 60 (35.3%) were females.
2- Regarding age, 54 (31.8%) were aged 50 years or more, while 43 (26.3%) were aged between 40 and <50. Only 8 (4.7%) patients were less than 20 years old.
3- Half of the patients 85 (50%) were in their induction phase of therapy, while 42 (24.7%) were in relapse.
4- Out of the 170 examined febrile neutropenic AML patients, 56 (32.9%) had length of hospital stay of 15-<20 days and only 8 patients (4.7%) had hospital stay of <5 days.
5- As regards neutrophil counts, 107 patients (63%) had neutrophil counts of >250 cells/µl and 28 (16.4%) had neutrophil counts of 100 to <150 cells/µl. Only one patient (0.6%) had neutrophil count of 150 to <200 cells/µl.
6- Concerning CVC insertion, 101 patients (60%) didn’t have any CVCs, while 69 (40%) had CVCs, where 53.6% of them had their CVCs inserted for 10-15 days. While 21 (30.4%) had CVCs inserted for < 5days.
7- Of the 170 examined patients, 107 patients (62.9%) had antibiotic therapy with β lactams in the month preceding bacteremia, while 131 (77.1%) had antibiotic therapy with β lactams at the onset of bacteremia.
8- Of the 200 collected samples, 111 (55.5%) showed bacterial growth, while 89 (44.5%) didn’t yield any bacterial growth.
9- Of the 111 isolated bacterial agents, 81 (72.9 %) were isolated from blood samples and 30 (27.1%) from pus and exudate swab samples.
10- Of the 111 isolated bacterial agents, 30 (27.1 %) were gram positive cocci and 81 (72.9%) were gram negative bacilli.
11- K. pneumoniae was the most commonly isolated bacterial agent 40 (36.0%).
12- S. aureus was the most frequently isolated gram-positive bacterial agent 19 (23.4%), where 18 (16.2%) were MRSA and only one (0.9%) was MSSA.
13- Of the 81 isolated bacterial agents from blood samples, 28 (34.5 %) were gram positive cocci and 53 (65.4%) were gram negative bacilli.
14- S. aureus was the most frequently isolated gram-positive bacterial agent from blood samples 19 (23.4%), where 18 (22.2%) were MRSA and only one (1.2%) was MSSA. This was followed by S. saprophyticus 6 (7.4%). S. epidermidis was the least encountered gram positive isolate 3 (3.7%) from blood samples.
15- Of the 30 isolated bacterial agents from pus and exudate swab samples, 2 (6.7%) were gram positive cocci and 28 (93.3%) were gram negative bacilli.
16- Two gram positive cocci were isolated from pus and exudate samples; these were S. saprophyticus and S. epidermidis representing 3.3% each.
17- Regarding the isolated gram negative bacterial agents from pus and exudate samples, K. pneumoniae was the most commonly isolated bacterial agent 15 (50%), followed by E. coli and P. aeruginosa 6 (20.0 %), and 5 (16.7), respectively. While A. baumannii was the least encountered gram-negative isolate from pus and exudate samples 2 (6.7%).
18- All MRSA isolates (100%) were resistant to cefoxitin, cefepime, amikacin, gentamycin and tetracycline, while 77.8% of isolates were resistant to ciprofloxacin and TMP/SMX.
19- All isolates of K. pneumonaie (100%) were resistant to cefuroxime, cefazolin, cefotaxime, aztereonam, ciprofloxacin and tetracycline, and were resistant to cefepime, while 50% of isolates were resistant to meropenem.
20- All isolates of E. coli (100%) were resistant to cefepime, piperacillin/tazobactam, cefuroxime, cefazoline, cefotaxime, ceftazidime, ciprofloxacin and tetracycline, while 83.3% were resistant to meropenem.
21- For P. aeruginosa isolates, the highest resistance percentages were recorded for ceftazidime (93.8%), followed by amikacin and ciprofloxacin (87.5%) each, while half of these isolates were resistant to cefepime.
22- No ESBLs have been detected.
23- Regarding cefepime resistance, it was noted that all isolates of MRSA (18), S. epidermidis (14), E.coli (16), A.baumannii (9) (100%) each were resistant to cefepime. While K.pneumoniae and P. aeruginosa represented 97.5% and 50%, respectively.
24- All isolates (100%) from patients who had neutrophil counts less than 200 cells/µl were cefepime resistant.
25- Out of the 55 patients who didn’t have CVCs, 40 (72.7%) yielded cefepime resistant isolates, while of the 56 patients who had CVCs, 54 (96.4%) of their bacterial isolates were cefepime resistant.
26- Of the isolates recovered from 83 patients who had antibiotic therapy with β lactams in the month preceding bacteremia, 77 (92.8%) were cefepime resistant, while among the 100 patients who had antibiotic therapy with β lactams at the onset of bacteremia, 88 (88.0%) yielded isolates that were cefepime resistant.
27- Bacterial cefepime resistance was significantly associated with neutrophil count of ≤250 cells/µl (P=0.039), length of hospital stay of more than12 days (P=0.010), CVC insertion (P=0.048) and antibiotic therapy with β lactams in the month preceding bacteremia (P=0.03).
28- As regards scoring system, patients without risk factors had a probability of 30.0% of cefepime resistant bacteria, while patients with one risk factor had a probability of 91.7% and patients with 2 or more risk factors had a probability of 98.5% of bacterial cefepime resistance.
It can be concluded from this study that:
1- BSIs prevailed among the studied febrile neutropenic AML patients.
2- Long hospital stay, CVC insertion and induction phase of therapy were significant risk factors which favor infectious complications in AML patients with FN.
3- Gram negative bacilli were the predominant pathogens causing bacteremia in febrile neutropenic AML patients.
4- K. pneumoniae was the most frequently isolated bacterial agent.
5- The majority of bacterial isolates showed high percentages of resistance to cefepime.
6- Bacterial cefepime resistance was significantly associated with neutrophil count of ≤250 cells/µl, length of hospital stay of more than12 days, CVC insertion, and antibiotic therapy with β lactams in the month preceding bacteremia.
7- K. pneumoniae and E. coli showed lower resistance percentages to carbapenems (meropenem) compared to cefepime.
8- Patients with 2 or more risk factors had a significantly higher probability of bacterial cefepime resistance.
from the results of this study, the following are recommended:
1. Continuous studying and monitoring of the spectrum of locally prevalent pathogens and their antimicrobial resistance patterns in febrile neutropenic AML patients, to evaluate and readjust empirical treatment whenever necessary.
2. Applying an easy to use scoring system for predicting bacterial resistance patterns before deciding the empirical administration of antibiotics (cefepime) should be considered by hematologists.
3. Due to high rates of cefepime resistance among isolated bacterial pathogens, further studies are needed to evaluate the use of other antibiotics including carbapenems as an antimicrobial monotherapy for febrile neutropenic AML patients especially for GNB infections.