Introduction
Acinetobacter baumannii is an emerging human
pathogen that causes hospital-acquired infections (1). Acinetobacter baumannii infection
could lead to a variety of illnesses such as pneumonia, meningitis
and endocarditis (2). In recent years,
the drug resistance rates of Acinetobacter baumannii are
increasing quickly worldwide, particularly with the appearance of
carbapenem-resistant Acinetobacter baumannii (3). Certain outbreaks of drug-resistant
Acinetobacter baumannii have been documented previously
(4,5).
The trend in increased antimicrobial resistance
limits the choice of effective antimicrobial agents.
Multidrug-resistant Acinetobacter baumannii and
pan-drug-resistant Acinetobacter baumannii have made
numerous currently available antimicrobial drugs ineffective
(2). Although several new
antimicrobial therapeutics, such as the generation of nitric
acid-producing nanoparticles (6),
gallium maltolate treatment (7) and
nanoemulsion (8), have been reported,
the therapeutic efficacy and safety for people requires further
investigation.
Currently, it is generally recognized that drug
resistance is an unavoidable consequence of misuse and overuse of
antibiotics. However, antibiotic treatments are not always the same
for the differences of medical cognition in different regions,
which leads to an eventual regional difference of bacterial
resistance (9).
The purpose of the present study was to report the
resistance to Acinetobacter baumannii, and analyze the
association between antibiotic use and resistance rates at a
general hospital in the east of China between 2010 and 2014.
Materials and methods
Bacterial isolates
The present study was performed at the Third
People's Hospital, an 800-bed, tertiary-care teaching hospital
affiliated with Southeast University (Yancheng, China). A total of
1,861 isolates were obtained from the clinical cultures between
January 1, 2010 until December 31, 2014. Identification was
performed using the VITEK 2 system (bioMerieux, Marcy l'Etoile,
France) in the microbiological laboratory of the hospital.
Antimicrobial susceptibility
Antimicrobial susceptibility testing was performed
using the disk diffusion method and susceptibility profiles were
determined using zone diameter interpretive criteria, as
recommended by the Clinical and Laboratory Standards Institute in
2011 (M100-S21). Mueller-Hinton agar (Oxoid, Thermo Fisher
Scientific, Inc., Waltham, MA, USA) was used for all susceptibility
tests. Escherichia coli American Type Culture Collection
(ATCC) 25922, Escherichia coli ATCC 3518, Klebsiella
pneumonia ATCC 700603, and Pseudomonas aeruginosa ATCC
7853 (all from ATCC, Manassas, VA, USA) were used as quality
control strains for each batch of tests. Duplicate isolates, which
were defined as repeated isolation, were of the same bacterial
species for the same patients with the same profile of antibiotic
susceptibility and they were excluded.
Antibiotic consumption
Antibiotic consumption data were collected from the
hospital information system. The antibiotic usage was standardized
based on the World Health Organization defined daily doses (DDDs)
per 100 bed days (http://www.whocc.no/atc_ddd_index/).
Statistical analysis
A time series analysis model was used to analyze the
association between the trend in quarterly antimicrobial
consumption and the rates of resistance. SPSS software version 19.0
(IBM, Corp., Armonk, NY, USA) was used to calculate the Pearson
correlation coefficient (r, s). Statistical significance was
two-sided and P<0.05 was considered to indicate a statistically
significant difference.
Results
Bacterial isolates
During the four years, 1,861 isolates were collected
and identified as Acinetobacter baumannii, which represented
10.33% of all the isolated strains. The strains were cultured from
respiratory samples (1,628 isolates, 87.5%), secretions and pus (84
isolates, 4.5%), blood (51 isolates, 2.7%), urine (44 isolates,
2.4%), abdominal fluid (20 isolates, 1.1%) and others (34 isolates,
1.9%).
Changes in resistance to different
antimicrobial agents
Table I summarizes the
results of the susceptibility tests of Acinetobacter
baumannii strains against antimicrobial agents. The majority of
the rates of antimicrobial resistance in Acinetobacter
baumannii were >60% during the four years. Resistance to
tobramycin, compound sulfamethoxazole, ampicillin/sulbactam and
ciprofloxacin decreased significantly in 2011 due to the
introduction of the antibiotic policy, a restriction of use of
numerous antibiotics. Resistance to levofloxacin, cefepime,
piperacillin/tazobactam, ceftazidime, imipenem/cilastatin and
gentamicin decreased slowly in 2012. However, all of these
rebounded in the first half of 2013, and subsequently decreased
slowly thereafter.
 | Table I.Resistance rates of Acinetobacter
baumannii strains against antibiotics. |
Table I.
Resistance rates of Acinetobacter
baumannii strains against antibiotics.
|
| Resistance rates,
% |
|---|
|
|
|
|---|
| Antibiotics | 2011a | 2011b | 2012a | 2012b | 2013a | 2013b | 2014a | 2014b |
|---|
|
Cefoperazone/sulbactam | 47.37 |
56.19 |
74.26 |
86.71 |
99.46 |
99.61 |
87.69 |
89.25 |
|
Ampicillin/sulbactam | 87.50 |
82.99 |
56.00 |
70.59 |
86.07 |
75.77 |
76.92 |
71.30 |
|
Imipenem/cilastatin | 81.03 |
81.90 |
84.13 |
72.79 |
90.48 |
80.41 |
78.32 |
69.44 |
| Meropenem | 80.77 |
79.05 |
92.08 |
93.73 |
96.71 |
95.75 |
97.83 |
97.85 |
| Biapenem | 81.25 |
82.74 |
83.17 |
83.33 |
97.37 |
95.24 |
95.85 |
95.98 |
| Tetracycline | 73.00 |
75.00 |
85.33 |
99.25 |
99.74 |
99.32 |
99.74 |
99.75 |
| Tigecycline | – | – | – | – |
66.67 |
68.85 |
67.89 |
68.76 |
| Tobramycin | 83.33 |
60.00 |
40.00 |
72.79 |
89.52 |
74.23 |
70.63 |
69.44 |
| Amikacin sulfate | 78.00 |
88.57 |
83.00 |
79.95 |
69.88 |
65.68 |
62.10 |
60.09 |
| Gentamicin | 91.38 |
92.38 |
86.51 |
76.47 |
90.48 |
77.32 |
74.83 |
70.37 |
| Levofloxacin | 89.66 |
80.95 |
86.51 |
72.06 |
89.52 |
75.77 |
71.33 |
70.37 |
| Ciprofloxacin | 83.33 |
73.98 |
64.00 |
75.74 |
92.86 |
79.38 |
80.42 |
72.22 |
| Cefoxitin | 98.08 |
99.05 | 100.00 |
99.50 |
99.48 | 100.00 | 100.00 | 100.00 |
| Cefepime | 94.83 |
87.62 |
88.89 |
76.47 |
92.38 |
77.84 |
80.42 |
72.22 |
| Cefobutazine | 99.50 | 100.00 | 100.00 | 100.00 |
99.50 | 100.00 |
99.30 |
99.07 |
| Ceftazidime | 98.28 |
90.48 |
92.80 |
79.41 |
95.52 |
86.08 |
85.31 |
80.56 |
| Cefotaxime | 89.68 |
91.43 |
98.00 |
98.43 |
99.13 | 100.00 | 100.00 | 100.00 |
| Ceftriaxone | 83.33 |
89.74 |
96.00 |
94.12 |
99.52 | 100.00 |
99.30 |
99.07 |
| Aztreonam | 83.33 |
90.00 |
96.00 | 100.00 |
99.52 | 100.00 |
99.30 |
99.07 |
|
Piperacillin/tazobactam | 86.21 |
85.71 |
81.60 |
75.00 |
90.48 |
78.35 |
79.72 |
71.30 |
| Compound
sulfamethoxazole | 83.33 |
67.85 |
52.00 |
73.53 |
90.48 |
75.26 |
74.13 |
62.04 |
| Nitrofurantoin | 91.67 |
93.76 |
96.76 | 100.00 |
99.52 | 100.00 | 100.00 | 100.00 |
Sulbactam is an irreversible inhibitor of
β-lactamase, which is commonly used in the local hospital, and the
increase of the resistance rates of cefoperazone/sulbactam was
evident. There are three carbapenem antibiotics; imipenem,
meropenem and biapenem. In 2011, the resistance rates of
imipenem/cilastatin, meropenem and biapenem was almost 80%, and
three years later, the resistance rates of meropenem and biapenem
increased by 17%, but the resistance rates of imipenem/cilastatin
decreased by 14%. Tigecycline was introduced in the hospital in
2013, and the resistance rate was <70%. Among a number of
cephalosporin drugs, the third and the fourth generation
cephalosporins, such as cefepime and ceftazidime, were active
agents, but the other cephalosporins were not.
Association of hospital antibiotic use
and resistance rate (%) of Acinetobacter baumannii
The high level of antibiotic resistance was
influenced by numerous factors; one of the most important factors
was the overuse and misuse of antibiotics. Several antibiotic usage
data were collected and were converted to DDDs, as shown in
Table II. During the investigation
period, the consumption of antibiotics varied from 192.60 to 25,412
DDDs. The usage of the second-generation cephalosporin drug ranked
first, followed by quinolone, aminoglycoside and others.
| Table II.Antibiotic administration between 2011
and 2014. |
Table II.
Antibiotic administration between 2011
and 2014.
| Antibiotics | 2011a | 2011b | 2012a | 2012b | 2013a | 2013b | 2014a | 2014b |
|---|
|
Cefoperazone/sulbactam |
|
|
|
|
|
|
|
|
|
DDDs | 954.34 | 1,197.56 | 1,363.88 | 1,291.13 | 1,350.35 | 1,429.13 | 1,853.25 | 1,970.38 |
| DDD/100
patient-days | 1.94 | 2.18 | 2.46 | 2.23 | 0.44 | 0.46 | 0.63 | 0.63 |
|
Imipenem/cilastatin |
|
|
|
|
|
|
|
|
|
DDDs | 204.35 | 242.42 | 224.22 | 226.14 | 263.75 | 260.75 | 314.01 | 328.75 |
| DDD/100
patient-days | 0.42 | 0.44 | 0.40 | 0.41 | 0.09 | 0.08 | 0.11 | 0.11 |
| Biapenem |
|
|
|
|
|
|
|
|
|
DDDs | 789.61 | 810.41 | 852.25 | 699.50 | 1,676.25 | 861.75 | 846.75 | 1,097.25 |
| DDD/100
patient-days | 1.61 | 1.47 | 1.54 | 1.20 | 0.55 | 0.28 | 0.28 | 0.35 |
| Amikacin
sulfate |
|
|
|
|
|
|
|
|
|
DDDs | 224.71 | 240.10 | 265.80 | 285.00 | 348.50 | 333.40 | 186.00 | 192.60 |
| DDD/100
patient-days | 0.46 | 0.44 | 0.48 | 0.49 | 0.19 | 0.11 | 0.06 | 0.06 |
| Gentamicin |
|
|
|
|
|
|
|
|
|
DDDs | 2,988.00 | 3,022.00 | 2,961.67 | 2,777.80 | 3,590.00 | 2,011.80 | 2,117.73 | 1,559.94 |
| DDD/100
patient-days | 6.09 | 5.49 | 5.35 | 4.80 | 1.18 | 0.65 | 0.72 | 0.50 |
| Levofloxacin |
|
|
|
|
|
|
|
|
|
DDDs | 13,750.00 | 12,966.00 | 14,168.60 | 12,068.00 | 17,226.00 | 13,628.20 | 13,405.80 | 13,240.80 |
| DDD/100
patient-days | 28.00 | 23.57 | 25.58 | 20.84 | 5.65 | 4.38 | 4.57 | 4.23 |
| Cefoxitin |
|
|
|
|
|
|
|
|
|
DDDs | 25,412.00 | 23,035.00 | 21,261.00 | 16,384.33 | 13,187.48 | 8,907.67 | 6,633.33 | 4,614.67 |
| DDD/100
patient-days | 51.76 | 41.88 | 38.38 | 28.30 | 4.33 | 2.86 | 2.26 | 1.47 |
| Cefepime |
|
|
|
|
|
|
|
|
|
DDDs | 542.01 | 435.46 | 554.25 | 436.25 | 676.88 | 652.25 | 762.25 | 769.75 |
| DDD/100
patient-days | 1.10 | 0.79 | 0.99 | 0.75 | 0.22 | 0.21 | 0.26 | 0.25 |
| Ceftazidime |
|
|
|
|
|
|
|
|
|
DDDs | 3,111.69 | 2,741.32 | 2,723.25 | 2,232.75 | 3,219.44 | 2,280.00 | 2,568.25 | 2,815.00 |
| DDD/100
patient-days | 6.34 | 4.98 | 4.92 | 3.86 | 1.06 | 0.73 | 0.88 | 0.90 |
|
Piperacillin/tazobactam |
|
|
|
|
|
|
|
|
|
DDDs | 2,940.30 | 2,917.24 | 2,480.92 | 2,575.53 | 6,233.70 | 8,773.78 | 8,148.18 | 8,162.52 |
| DDD/100
patient-days | 5.99 | 5.30 | 4.48 | 4.55 | 2.05 | 2.82 | 2.78 | 2.59 |
There were statistically significant associations
between the uses of several antibiotics and resistance in
Acinetobacter baumannii to the drug as shown in Table III. The gentamicin usage was
significantly correlated with resistance in Acinetobacter
baumannii to this drug (rs=0.870, P<0.01). Furthermore, the
association between the use of various types of antibiotic and
resistance rate (%) of Acinetobacter baumannii was analyzed,
as shown in Table IV. There were
statistically significant associations between the resistance rate
of biapenem and usage of aminoglycosides (r=−0.924, P<0.01).
| Table III.Association between the antibiotic
use and resistance rate (%) of Acinetobacter baumannii. |
Table III.
Association between the antibiotic
use and resistance rate (%) of Acinetobacter baumannii.
| Antibiotics | Pearson
association | P-value
(two-tailed) |
|---|
|
Cefoperazone/sulbactam | 0.601 | 0.115 |
|
Imipenem/cilastatin | 0.601 | 0.115 |
| Biapenem | 0.097 | 0.097 |
| Amikacin
sulfate | 0.138 | 0.744 |
| Gentamicin | 0.870a | 0.005 |
| Levofloxacin | 0.654 | 0.079 |
| Cefoxitin | −0.741b | 0.035 |
| Cefepime | −0.324 | 0.433 |
| Ceftazidime | 0.748b | 0.033 |
|
Piperacillin/tazobactam | 0.876a | 0.006 |
| Table IV.Association between the use of
various types of antibiotics and the resistance rates (%) of
Acinetobacter baumannii. |
Table IV.
Association between the use of
various types of antibiotics and the resistance rates (%) of
Acinetobacter baumannii.
|
| Resistance rates,
% |
|---|
|
|
|
|---|
| Defined daily
doses | Biapenem |
Cefoperazone/sulbactam | Amikacin
sulfate |
|---|
|
Aminoglycosides |
|
|
|
| Pearson
association | −0.924a | −0.842b | 0.719 |
| P-value
(two-tailed) | 0.009 | 0.035 | 0.107 |
| Cephalosporins |
|
|
|
| Pearson
association | −0.785 | −0.505 |
0.875a |
| P-value
(two-tailed) | 0.064 | 0.307 | 0.004 |
Discussion
The drug resistance data between 2010 and 2014
showed that the resistance rates of the majority of antimicrobial
drugs was >70% in Acinetobacter baumannii. Thus, it
became more difficult to cure Acinetobacter baumannii
infection, and one more active agent is required based on the
resistance experience. The antibiotic policy was introduced in the
hospital in 2011, and the majority of antibiotics used were
restricted and guided by rules. The policy promoted the rational
use of antimicrobial drugs, and certain antimicrobial resistant
rates periodically reduced. However, all the antibiotic resistance
rates did not decrease at the same time to cure infection, and
there was a fluctuation. These drops and fluctuations of the
resistance rates of certain antibiotics were closely associated
with the usage of antibiotics according to the statistical
analysis, confirming that an antimicrobial susceptibility test is
important in providing useful information for effective treatment,
and occasionally more than one antibiotic is required to cure
Acinetobacter baumannii infection. To decrease the spread of
Acinetobacter baumannii infections, surveillance is also
important to restrict the abuse of antibiotics and guide the
rational usage of antibiotics.
Acknowledgements
The present study was supported by a project grant
from Yancheng Medical Science and Technology Development Project
(grant no. YK2013056).
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