Mohsen et al. Antimicrobial Resistance and Infection Control (2017) 6:63
DOI 10.1186/s13756-017-0225-9
RESEARCH
Open Access
Emerging antimicrobial resistance in early
and late-onset neonatal sepsis
Lamiaa Mohsen1,4, Nermin Ramy1,4*, Dalia Saied1,4, Dina Akmal1,4, Niveen Salama1,4, Mona M. Abdel Haleim2,4
and Hany Aly3
Abstract
Background: Compared to developed countries, the use of antimicrobials in Egypt is less regulated and is available
over the counter without the need for prescriptions. The impact of such policy on antimicrobial resistance has not
been studied. This study aimed to determine the prevalence of early and late onset sepsis, and the frequency
of antimicrobial resistance in a major referral neonatal intensive care unit (NICU).
Methods: The study included all neonates admitted to the NICU over a 12-month period. Prospectively
collected clinical and laboratory data were retrieved, including blood cultures and endotracheal aspirate
cultures if performed.
Results: A total of 953 neonates were admitted, of them 314 neonates were diagnosed with sepsis; 123 with early
onset sepsis (EOS) and 191 with late onset sepsis (LOS). A total of 388 blood cultures were obtained, with 166 positive
results. Total endotracheal aspirate samples were 127; of them 79 were culture-positive. The most frequently isolated
organisms in blood were Klebsiella pneumoniae (42%) and Coagulase negative staphylococcus (19%) whereas in
endotracheal cultures were Klebsiella pneumoniae (41%) and Pseudomonas aeruginosa (19%). Gram negative organisms
were most resistant to ampicillins (100%), cephalosporins (93%–100%) and piperacillin-tazobactam (99%) with
less resistance to aminoglycosides (36%–52%). Gram positive isolates were least resistant to vancomycin (18%).
Multidrug resistance was detected in 92 (38%) cultures, mainly among gram negative isolates (78/92).
Conclusions: Antibiotic resistance constitutes a challenge to the management of neonatal sepsis in Egypt.
Resistance was predominant in both early and late onset sepsis. This study supports the need to implement
policies that prohibits the non-prescription community use of antibiotics.
Keywords: Blood cultures, Tracheal aspirate, Klebsiella pneumoniae, Gram positive cocci, Antibiotic susceptibility, Early
onset sepsis, Late onset sepsis, Multidrug resistance, Neonatal sepsis
Background
Neonatal sepsis is a major health problem worldwide [1].
Neonates are more at risk for bacterial sepsis, with a
global prevalence of 1 to 10 per 1000 live births [2].
Sepsis problem is much higher in the developing than in
the developed countries, with sepsis-related mortality
rate as high as 50% for untreated newborns.
Neonatal sepsis is a clinical syndrome in an infant
28 days of life or younger, manifesting with a diversity of
non-specific systemic signs and symptoms and isolation
* Correspondence: nerminramy74@gmail.com
1
Department of Pediatrics, Faculty of Medicine, Cairo University, Cairo, Egypt
4
New Children Hospital, (Abu El Rish), Cairo University Hospitals, Ali Basha
Ebrahim, PO Box 11562, Cairo, Egypt
Full list of author information is available at the end of the article
of a pathogen from the bloodstream [3]. According to
inception, early onset sepsis (EOS) refers to infections
during the first 72 h of life that is usually related to
intrapartum transmission from mothers; whereas late
onset sepsis (LOS) refers to postnatal acquisition of
infections after the first 3 days of life [4]. Pathogens
encountered in neonatal sepsis vary worldwide; reports
from developing countries more commonly show Gram
negative organisms [5, 6], although Gram positive organisms have been also reported [6–8]. The susceptibility
patterns for early neonatal sepsis typically differs from
late neonatal sepsis; more resistant organisms are
expected from hospital acquired late sepsis when compared to vertically transmitted, community acquired,
© The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0
International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and
reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver
(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Mohsen et al. Antimicrobial Resistance and Infection Control (2017) 6:63
Page 2 of 9
early sepsis. However, a report from a developing country showed some resistant organisms to cause early
neonatal sepsis [9]. Resistant organisms can potentially
grow in the community with inappropriate use of antibiotics that is typical in some developing countries. Therefore, in this current study, investigators aimed to examine
the microbiological patterns of early and late neonatal
sepsis and to specify their antibiotic susceptibility.
Microbiological sampling
Methods
Sample processing
Patients
Specimens were processed on arrival to the laboratory.
Enriched media used included: blood, MacConkey and
chocolate agar plates. These were inoculated, incubated
at 37 °C, and examined for growth at 24–48 h. Isolates,
if any, were identified by: Gram staining, colony characteristics, and biochemical properties including catalase, DNAse agar, mannitol salt agar, and hemolysis
on blood agar plates, for Gram positive isolates, and
triple sugar iron (TSI), lysine iron agar (LIA), motility
indole, ornithine (MIO), citrate, urease and oxidase
for Gram negative bacilli [12]. All media and biochemical
reactions were systematically quality controlled according
to the standards by the American Type Culture Collection. Antibiotic susceptibility tests were performed by
Kerby-Bauer disc diffusion method according to the standards of Clinical and Laboratory Standards Institute
(CLSI). The antibiotic discs used represented different
groups of antibiotics. The inhibition zones were measured
and interpreted according to the CLSI recommendations
[13]. Multi drug resistant (MDR) bacteria were defined by
resistance to three or more antimicrobial classes [14].
This is a retrospective study of a prospectively collected
data at the neonatal intensive care unit (NICU) of Cairo
University Children’s Hospital in Egypt, conducted over
a 12-month- period. The study was approved by the
Ethical Committee of the hospital. Infants were included
if they were diagnosed with microbiological bacteremia,
and/or clinical sepsis that was accompanied by nonmicrobiological laboratory values suggestive of infections. Infants were considered to have sepsis if they had
a score of 3 or more of the following hematologic findings: i) abnormal total leucocyte count, ii) abnormal
total neutrophil (PMN) count, iii) increased immature
PMN count, iv) increased immature to total PMN ratio,
v) immature to mature PMN ratio ≥ 0.3, vi) platelets
count ≤150,000/mm3, and vii) pronounced degenerative
changes in PMNs [10]. Infants were classified into two
groups according to the timing of sepsis diagnosis: EOS
diagnosed ≤72 h of life and LOS diagnosed >72 h of
life. Demographic, clinical, and laboratory data were
retrieved for all included infants.
For blood cultures, at least 1 ml of blood sample was
obtained from a peripheral vein under aseptic precautions. Blood samples were incubated in blood culture
incubator (BACTEC- 9050, Beckton-Dickenson, Franklin
Lakes, New Jersey, USA). ETA samples were obtained by
direct endotracheal suction of respiratory secretions
using sterile endotracheal suction catheters into sterile
suction trap.
Statistical analysis
Infectious control management
All admitted infants received a limited sepsis work up
that included complete blood count, C-reactive protein,
and blood culture. Empiric parenteral antibiotics were
initiated for 3 days while awaiting blood culture results.
Sepsis work ups were repeated during hospital stay
whenever an infant displayed clinical signs suggestive for
sepsis. Infants were considered to have bloodstream
infection if they had at least one blood culture positive
for organisms known to cause bacteremia [11]. For other
organisms that may cause true bacteremia or may
represent skin contamination, infection was considered if the same organism was recorded from at least
two blood cultures. Endotracheal aspirate (ETA) cultures
were occasionally obtained from mechanically ventilated
cases if they displayed clinical signs suggestive of
ventilator associated pneumonia such as increased
oxygen requirement, increased ventilator support settings, worsening radiographic findings, and changes in
tracheal aspirate volume, color or consistency.
All statistical procedures were performed using the
Statistical Package for Social Science (SPSS) for windows
version 16.0 (SPSS Inc., Chicago, Illinois, USA). Descriptive analyses were expressed as mean ± standard
deviation (SD) for quantitative variables, and percentages (%) for categorical variables. Differences in distribution for categorical variables were done using the
Chi square test.
Results
Nine hundred fifty three cases were admitted during the
study period; of them 314 (32.9%) neonates were diagnosed with sepsis based on clinical signs and/or microbiological laboratory. Early onset sepsis was detected in
123 cases and late onset sepsis in 191 cases. The
characteristics of the study population are presented
in Table 1. Seventy-seven cases were admitted solely
for sepsis whereas 237 had other associated morbidities as
shown in Table 2. Sepsis presented more frequently in
males than females (178 vs. 136).
Mohsen et al. Antimicrobial Resistance and Infection Control (2017) 6:63
Table 1 Demographic characteristics of the study population
Variable
Early onset sepsis
(n = 123)
Late onset sepsis
(n = 191)
≤ 28 weeks (n) (%)
10 (8.13%)
12 (6.28%)
> 28–32 weeks (n) (%)
40 (32.52%)
> 32–36 weeks (n) (%)
32 (26.01%)
- Gestational age (weeks)
> 36 weeks (n) (%)
- Male/Female (n)
Table 3 Organisms in blood cultures of infants with early and
late onset sepsis (n = 166)
Blood culture
Isolated organism
Early onset
sepsis
Late onset
sepsis
Total
21 (10.99%)
-Klebsiella pneumoniae
20
49
69 (41.56%)
43 (22.51%)
-Pseudomonas aeruginosa
7
14
21 (12.65%)
41 (33.33%)
115 (60.20%)
-Acinetobacter
3
10
13 (7.83%)
72/51
106/85
-CONS
15
16
31 (18.67%)
-MRSA
2
7
9 (5.42%)
-B streptococci
0
4
4 (2.40%)
-Streptococcus pneumoniae
1
0
1 (0.60%)
-Staphylococcus aureus
0
3
3 (1.80%)
-Escherichia coli
0
4
4 (2.40%)
-Enterobacter
1
7
8 (4.81%)
-Salmonella
0
1
1 (0.60%)
-Stenotrophomonaes
0
2
2 (1.20%)
- Age on admission (days)
(mean ± SD)
2.41 ± 4.1
9.96 ± 9.2
- Length of hospital stay(days)
(mean ± SD)
16.46 ± 16.48
18.68 ± 16.61
38 (30.8%)
32 (16.8%)
- Outcome (deaths) (n) (%)
Page 3 of 9
A total of 388 blood specimens were cultured from
our 314 septic neonates, with more than one culture
obtained from the same case in some occasions, with
166 microbiologically positive cultures; of them 49
cultures for cases with EOS and 117 cultures for cases
with LOS. The most common organisms for EOS and
LOS were gram negative bacilli (31/49 and 87/117
respectively), mainly Klebsiella pneumoniae spp. (n = 20
for EOS, and 49 for LOS). Table 3 represents the isolated
organisms in the studied population.
A total of 127 endotracheal aspirates (ETA) were
obtained during the study period from 58 patients with
79 positive cultures; of them 24 cultures belonged to
cases with EOS and 55 with LOS. The most prominent
Table 2 Clinical presentations and diagnoses among studied
cases with suspected sepsis
Clinical manifestation/ diagnosis
Number (%)
- Poor suckling & sluggish reflexes
77 (24.5%)
- Respiratory distress
91 (29.0%)
- Pulmonary hypertension
3 (1.0%)
- Meconium aspiration syndrome
4 (1.3%)
- Apnea
35 (11.2%)
- Congenital heart disease
6 (1.9%)
- Neonatal jaundice
19 (6.1%)
- Neonatal convulsions
12 (3.8%)
- Hypoxic ischemic encephalopathy
11 (3.5%)
- Neonatal hypoglycemia
7 (2.2%)
- Multiple congenital anomalies
10 (3.2%)
- Low birth weight
10 (3.2%)
- Neonatal Pneumonia
15 (4.8%)
- Bleeding tendency or hemorrhage
14 (4.5%)
- Total
314(100%)
-Total
166
CONS coagulase negative staphylococci, MRSA methicillin resistant
staphylococcus aureus
organisms in ETA cultures were Klebsiella pneumoniae
in cases with EOS (22/24) and Pseudomonas aeruginosa
(21/55) in LOS cases (Table 4). Organisms isolated from
ETA cultures differed from those in blood cultures in
29% of cases.
Antimicrobial sensitivity and resistance patterns were
assessed for all 245 isolated bacteria; 166 blood cultures
and 79 ETA cultures. Tables 5 and 6 present the susceptibility patterns of gram negative bacilli and gram positive cocci respectively. Gram negative bacilli showed
highest resistance to ampicillins (ampicillin- sulbactam,
100% and amoxicillin-clavulanate, 97%), cephalosporins
(cefotaxime, 93%, ceftazidime, 96%, cefoperazone, 95%,
ceftriaxone, 99%, cefuroxime, 100%), and piperacillinTable 4 Organisms isolated in endotracheal aspirate cultures of
infants (n = 79)
ETA culture
Isolated organism
Total
-Klebsiella Pneumoniae
36 (45.6%)
-Pseudomonas aeruginosa
23 (29.1%)
-Acinetobacter
11 (13.9%)
-Escherichia coli
2 (2.5%)
-Enterobacter
4 (5.1%)
-CONS
2 (2.5%)
-Staphylococcus aureus
1 (1.3%)
Total
79
CONS coagulase negative staphylococci
45(43%)
12(27.3%)
8(33.3%)
1(100%)
1(16.7%)
3(25%)
0
Meropenem
34(32.4%)
20(45.5%)
10(41.7%)
0
0
4(33.3%)
1(50%)
105(100%)
44(100%)
24(100%)
1(100%)
6(100%)
12(100%)
2(100%)
Gentamicin
63(60%)
21(47.7%)
7(29.2%)
1(100%)
1(16.7%)
8(66.7%)
0
Kl(105)
Pseudomonas (44)
Acinetobacter (24)
Salmonella (1)
E coli (6)
Enterobacter (12)
Stenotrophomonas(2)
Kl (105)
Pseudomonas (44)
Acinetobacter (24)
Salmonella (1)
E coli (6)
Enterobacter(12)
Stenotrophomonas(2)
2(100%)
12(100%)
6(100%)
1(100%)
21(87.5%)
39(88.6%)
103(98.1%)
Cefoperazone
2(100%)
12(100%)
4(66.7%)
1(100%)
20(83.3%)
39(88.6%)
103(98.1%)
Cefotaxime
2(100%)
8(66.7%)
5(83.3%)
1(100%)
14(58.3%)
28(63.6%)
86(81.9%)
Cefepime
2(100%)
12(100%)
5(83.3%)
1(100%)
21(87.5%)
41(93.2%)
105(100%)
Ceftazidime
2(100%)
11(91.7%)
6(100%)
1(100%)
24(100%)
43(97.7%)
101(96.2%)
Amoxicillinclavulanate
1(50%)
2(16.7%)
0
0
9(37.5%)
17(38.6%)
22(21%)
Imipenem
2(100%)
12(100%)
6(100%)
1(100%)
24(100%)
44(100%)
103(98.1%)
Ceftriaxone
ND
ND
ND
ND
ND
ND
ND
Vancomycin
ND Sensitivity was not done, E coli Escherichia coli, Klebsiella Klebsiella pneumoniae, Pseudomonas Pseudomonaas aeruginosa
Amikacin
Ampicillinsulbactam
Organism (number)
Table 5 Resistance of gram negative bacilli to various antimicrobials
2(100%)
10(83.3%)
2(33.3%)
0
19(79.2%)
37(84.1%)
86(81.9%)
Cotrimoxazole
2(100%)
5(41.7%)
2(33.3%)
0
8(33.3%)
22(50%)
48(45.7%)
Ciprofloxacin
ND
ND
ND
ND
ND
ND
ND
Erythromycin
ND
ND
ND
ND
ND
ND
ND
Clindamycin
1(50%)
11(91.7%)
2(33.3%)
1(100%)
16(66.7%)
38(86.4%)
82(78.1%)
Cefoxitin
2(100%)
3(25%)
1(17%)
0
7(29%)
8(18%)
25(24%)
Levofloxacin
ND
ND
ND
ND
ND
ND
ND
Rifampicin
2(100%)
12(100%)
6(100%)
1(100%)
24(100%)
44(100%)
105(100%)
Cefuroxime
2(100%)
12(100%)
6(100%)
1(100%)
24(100%)
44(100%)
103(98.1%)
Piperacillintazobactam
Mohsen et al. Antimicrobial Resistance and Infection Control (2017) 6:63
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16(48.5%)
3(33.3%)
2(50%)
1(100%)
3(75%)
Meropenem
28(85%)
9(100%)
2(50%)
1(100%)
4(100%)
33(100%)
9(100%)
4(100%)
1(100%)
4(100%)
Gentamicin
18(55%)
7(77.8%)
0
0
4(100%)
CONS (33)
MRSA (9)
B streptococcus (4)
St. pneumonie (1)
Staph aureus (4)
CONS (33)
MRSA (9)
B streptococcus (4)
St. pneumonie (1)
Staph aureus (4)
4(100%)
1(100%)
4(100%)
9(100%)
33(100%)
Cefoperazone
4(100%)
1(100%)
3(75%)
9(100%)
31(93.9%)
Cefotaxime
4(100%)
0
2(50%)
9(100%)
29(88%)
Cefepime
4(100%)
1(100%)
3(75%)
9(100%)
31(93.9%)
Ceftazidime
0
0
3(75%)
9(100%)
26(79%)
Amoxicillinclavulanate
4(100%)
1(100%)
2(50%)
8(88.9%)
28(84.8%)
Imipenem
4(100%)
1(100%)
4(100%)
9(100%)
33(100%)
Ceftriaxone
0
0
1(25%)
0
8(24.2%)
Vancomycin
4(100%)
1(100%)
4(100%)
8(89%)
27(82%)
Cotrimoxazole
3(75%)
0
3(75%)
8(88.9%)
25(75.8%)
Ciprofloxacin
4(100%)
1(100%)
4(100%)
7(78%)
28(85%)
Erythromycin
2(50%)
1(100%)
3(75%)
3(33%)
18(55%)
Clindamycin
ND sensitivity was not done, CONS coagulase negative staphylococci, MRSA methicillin resistant staphylococcus aureus, St streptococcus, Staph. aureus Staphylococcus aureus
Amikacin
Ampicillinsulbactam
Organism (number)
Table 6 Resistance of gram positive cocci to various antimicrobials
3(75%)
1(100%)
3(75%)
9(100%)
25(76%)
Cefoxitin
ND
ND
ND
ND
ND
Polymyxin
4(100%)
1(100%)
4(100%)
7(78%)
22(67%)
Levofloxacin
2(50%)
1(100%)
4(100%)
3(33%)
15(46%)
Rifampicin
4(100%)
1(100%)
4(100%)
9(100%)
33(100%)
Cefuroxime
4(100%)
1(100%)
4(100%)
9(100%)
33(100%)
Piperacillintazobactam
Mohsen et al. Antimicrobial Resistance and Infection Control (2017) 6:63
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Mohsen et al. Antimicrobial Resistance and Infection Control (2017) 6:63
tazobactam, 99%. Less resistance was evident to aminoglycosides, mainly amikacin (36%) and gentamicin
(52%), as well as carbapenems (imipenem, 26% and
meropenem, 64%). Least resistance to quinolones
(levofloxacin, 24%). Gram positive cocci showed highest
resistance to ampicillins (amoxicillin-sulbactam, 100% and
amoxicillin-clavulanate, 75%), cephalosporins (ceftazidime,
94%, cefoperazone, 100%, cefepime, 86%, ceftriaxone, 100%,
cefuroxime, 100%, cefoxitin, 80%), carbapenems (imipenem,
84%, meropenem, 86%), piperacillin-tazobactam (100%),
and erythromycin (86%). Less resistance was evident to
aminoglycosides (amikacin, 49%, gentamicin, 57%), quinolones (ciprofloxacin, 77%, levofloxacin, 75%), clindamycin
(53%), and rifampicin (49%). Least resistance among gram
positive bacteria was found to vancomycin (18%). Multidrug resistance was detected in 67 cases; 18 with EOS and
49 with LOS, and in 92 (37.6%) cultures, mainly among
gram negative isolates (78/92).
Discussion
Neonatal sepsis, a life-threatening condition, needs
immediate empirical antimicrobial therapy. It is important to choose an antibiotic combination that covers the
most common pathogens [15]. Blood culture remains
the gold standard for diagnosis of neonatal sepsis,
despite its low sensitivity which may be due to small
volume of blood sample, or empirical antibiotics prior to
sampling [16].
We observed the emergence of multi drug resistance among cases of EOS, which has not been frequently mentioned. A previous study from India stated
that multidrug resistant organisms were leading causes of
early as well as late onset sepsis [17]. Even studies from
Egypt addressing this problem studied multi drug resistance either collectively [18] or in relation to late
onset sepsis only [19]. The worrisome rise in levels of
antimicrobial resistance among pathogens retrieved
from NICUs highlight the needs for better understanding of the problem of early onset sepsis and
implementing strategies to combat, especially in countries with limited resources [20].
In the current study, the overall incidence of suspected
sepsis was 32.9%. These results are comparable to other
studies from Egypt [21, 22], but are better than a previous report in 2001 wherein the rate of sepsis exceeded
50% [23], which may be due to better awareness and
adherence to infection control measures.
In this study, the overall mortality in septic neonates
was 22.3%. This value is lower than sepsis related deaths
reported in other studies from Egypt [21, 23], however,
several studies reviewed from different developing
Page 6 of 9
countries showed a wide range of infection related neonatal mortality ranging between 8 and 80% [24]. A sepsis
related mortality of 19% was reported in studies from
east Africa [25, 26].
In this work, the incidence of LOS was higher than
that of EOS. Comparable findings were reported in
other studies from Egypt and South Africa [21, 27].
The opposite was found in studies from Nepal [28]
and Iran [29].
Suspected sepsis was confirmed by blood culture,
yielding different bacterial growths in only 166/388
cultures (42.8%). This rate is in the vicinity to those of
other studies from Egypt [21] and other developing
African and Asian countries [25, 30]. Despite being the
gold standard for diagnosing sepsis, blood cultures suffer
from low sensitivity, postulated reasons include prior
use of antibiotics, insufficient or wrong sampling, poor
transport conditions, and slow-growing or fastidious
bacteria [31]. Also, some culture negative patients might
be due to non-bacterial causes as fungi, viruses and
parasites [32]. ETA cultures yielded matching results to
blood cultures in 38% of simultaneous cultures and grew
different organisms in 29% of cases. Authors showed ETA
cultures to be of no value in predicting pathogens causing
septicemia in ventilated infants [33]. Higher percentages
of matching cultures in this study may be explained by
higher simultaneous negative cultures.
Gram negative bacilli were more frequently encountered than gram positive cocci, with Klebsiella pneumoniae being the most commonly isolated organism both
in blood and ETA cultures (42% and 41% respectively),.
These results were consistent in multiple reports from
Egypt over two decades [22, 34, 35]. However, other
reports from Egypt showed CONS as the leading cause
of sepsis in 2006 [36], 2010/2011 [37], and 2011/2012
[21]. These results support the fact that the diversity of
organisms causing sepsis varies from region to another
and changes over time even in the same place [38].
The frequency of gram negative pathogens varied
from 31% to 63% with Klebsiella pneumoniae, Pseudomonas aeruginosa and Escherichia coli being the predominant organisms in almost all countries of Latin
America [39]. Several other studies in a diversity of
developing countries showed that gram negative bacteria were responsible for most cases of neonatal sepsis [29, 30, 40, 41]. Although some authors state that
gram-positive bacteria are the most commonly encountered in NICU patients [42, 43], yet case fatalities are highest for gram-negatives [44]. Others have
indicated increasing incidence of gram-negative bacterial infections in NICUs [45].
Among gram negative organisms, Klebsiella pneumoniae is increasingly emerging as a common bacteria in
hospital settings [46].
Mohsen et al. Antimicrobial Resistance and Infection Control (2017) 6:63
The first line of empirical treatment in this NICU is
Ampicillin-sulbactam combined with cephalosporins or
aminoglycosides. In the absence of clinical improvement,
antibiotics are changed to carbapenems and vancomycin
until the blood culture results are available. Quinolones
are used in culture-proven sepsis with multidrug resistant organisms. In this study, gram negative organisms
were most resistant to ampicillins, cephalosporins, and
piperacillin- tazobactam. Less resistance was observed to
aminoglycosides and carbapenems with least resistance
to levofloxacin. Several studies showed high resistance
to ampicillin and amoxicillin, aminoglycosides, and
different classes of cephalosporins [41, 47]. Even within
the aminoglycoside spectrum, some authors found amikacin (which was less used in their units) more sensitive
than gentamicin (which was more commonly used) [47].
Two studies in sub-Saharan Africa and Asia revealed
resistance of the two common pathogens Klebsiella and
Staphylococcus aureus to almost all commonly used
antibiotics in one study [48], and Klebsiella pneumoniae
median resistance to ampicillins and cephalosporins in
94 and 84% of cases in Asia and 100 and 50% in Africa
[49] in the other study. Although short courses of antimicrobials as carbapenems and cephalosporins especially
third generation cover a broad spectrum of bacteria, yet
their extended use caused the emergence of extended
spectrum β lactamase producing gram negative bacteria.
This confers resistance to penicillins and cephalosporins
and often coexisting with resistance to other categories of
antibiotics as quinolones and aminoglycosides [50–53]. In
Egypt, gram negative bacteria were resistant to ampicillin, amoxicillin clavulanate and cephalosporins, with
highest sensitivity to either or both carbapenems and
quinolones [21, 35, 37].
The increasing multidrug resistant gram negative bacteria with relative deficiency of new antibiotics to combat
led to the revival of other classes of drugs as polymyxins,
which are active against Acinetobacter species, Pseudomonas aeruginosa, Klebsiella species, and Enterobacter
species [54].
In this work, gram positive organisms were most resistant to ampicillins (mainly ampicillin-sulbactam), a wide
variety of cephalosporins (ceftazidime, cefoperazone, cefepime, ceftriaxone, cefoxitime, cefuroxime), carbapenems,
piperacillin-tazobactam, and erythromycin. They were less
resistant to aminoglycosides, quinolones, clindamycin,
and rifampicin and least resistant to vancomycin.
In one study in India, rifampicin was effective against
Staphylococcus aureus [55]. Other drugs as erythromycin
show rising resistance among streptococci species (mainly
group B streptococci, group A streptococci, Streptococcus
pyogenes, and Streptococcus pneumoniae) and Staphylococcus aureus [56]. Similarly, in current work, erythromycin
resistance was highest against Streptococcus pneumoniae,
Page 7 of 9
group B streptococci. There is an increasing incidence of
multi drug resistant gram positive organisms [57], as well
as increasing vancomycin resistant isolates [58], however;
vancomycin still is an important first-line antimicrobial for
treatment of serious infections as Methicillin-Resistant
Staphylococcus aureus [59]. In our study, we found high
resistance to fluoroquinolones among gram positive
organisms. This resistance is emerging due to their extensive and increasing use in medical practice and was stated
in the literature to be greatest in Staphylococcus aureus
isolates especially methicillin resistant strains [60].
Conclusion
This study demonstrated a high prevalence of gram negative bacilli sepsis and tracheal colonization. Both gram
negative bacilli and gram positive cocci were highly resistant to multiple broad-spectrum antimicrobials. Resistance
was the highest against antibiotics used frequently in the
NICU as the first line or the second line empirical treatment. It is worrisome to discover that pan drug resistance
was not restricted to LOS; infants admitted from the community with early onset sepsis had a high resistance index
to the multiple antibiotics. Of note, antibiotics in Egypt
are available over the counter and do not require a physician’s prescription. This study calls for global regulations
to restrict the use of antimicrobials in the community as
well as in the hospital setting.
Abbreviations
CLSI: Clinical and Laboratory Standards Institute; EOS: Early onset sepsis;
ETA: Endotracheal aspirate; LIA: Lysine iron agar; LOS: Late onset sepsis;
MDR: Multi drug resistance; MIO: Motility indole ornithine; NICU: Neonatal
ntensive Care Unit; PMN: Polymorph nuclear leucocytes; spp.: Species;
SPSS: Statistical Package for Social Science; TSI: Triple sugar iron
Funding
This work did not receive any funding from any source.
Availability of data and materials
The raw data can be made available to interested researchers by the authors
of this article if requested.
Authors’ contributions
LM designed the study and reviewed the manuscript for important
intellectual content. NR analyzed the data and wrote the manuscript. DS
took part in data analysis and reviewed the manuscript. MMA performed
experimental works. DA and NS were responsible for collecting the data. HA
critically revised the manuscript and participated in writing. All authors read
and approved the final manuscript.
Competing interests
The authors declare they have no competing interests.
Consent for publication
Not applicable.
Ethics approval and consent to participate
Due to the retrospective nature of the current study, no informed concent
was taken from the caregivers of neonates included, however, consent for
sample withdrawal was not required as they are part of routine
management. This work has been approved by the Ethical Committee of
Cairo University Children Hospital.
Mohsen et al. Antimicrobial Resistance and Infection Control (2017) 6:63
Page 8 of 9
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21.
Author details
1
Department of Pediatrics, Faculty of Medicine, Cairo University, Cairo, Egypt.
2
Department of Clinical and Chemical Pathology, Cairo University, Cairo,
Egypt. 3Division of Neonatology, the George Washington University and
Children’s National Health System, 900 23rd Street, N.W. Suite G2092,
Washington, DC 20037, USA. 4New Children Hospital, (Abu El Rish), Cairo
University Hospitals, Ali Basha Ebrahim, PO Box 11562, Cairo, Egypt.
Received: 7 April 2017 Accepted: 9 June 2017
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