Introduction
The extensive use of antibiotics and the gradual
increase of different types of drugs have made bacteria resistant
to drugs (1,2). Appropriate selection of antibiotics for
the treatment of the majority of severe microbial infections. The
emerging resistance of different pathogenic microbes to drugs
refers to multidrug-resistant, extensively drug-resistant or
pandrug-resistant bacteria.
The drug resistance of acinetobacter is more severe
due to the emergence of pan-resistant Acinetobacter
baumannii, which is pan-resistant to antibacterial agents in
current routine testing (3,4). Consequently, the treatment of
pan-resistant Acinetobacter baumannii has become a worldwide
issue. Pan-resistant, Acinetobacter baumannii is defined as
the bacterial strain that is pan-resistant to common
anti-gram-negative antibiotics such as penicillin, cephalosporin,
monocyclic lactams, aminoglycosides, quinolones, carbapenems,
tetracyclines and sulfonamides (5).
To circumvent infections caused by this infectious
bacteria, Xiangyang Hospital has applied combined treatment of
traditional Chinese and Western medicine to pan-resistant
Acinetobacter baumannii cases in intensive care unit
patients during the period January 1, 2008 to December 31, 2009,
which has achieved promising effects. The present study examined
the effect of the combined therapy of sulperazone supplemented with
tanreqing, and sulperazone, as monotherapy.
Materials and methods
Patients
The present study included 30 patients suffering
from pulmonary infection with pan-resistant Acinetobacter
baumannii in the Xiangyang Hospital during the period January
1, 2008 to December 31, 2009.
Microbiological methods
Clinical samples were collected aseptically. The
sputum specimens were taken through the artificial airway and a
drug sensitivity test was performed according to the agar diffusion
method to determine their sensitivity to 19 antibacterial
drugs.
Clinical data
The extracted pan-resistant Acinetobacter
baumannii was observed immediately and was divided into
colonized bacteria and infectious bacteria according to the
hospital infection diagnostic criteria established by the Ministry
of Health. The extracted bacterium was defined as colonized
bacteria if it did not qualify for the diagnostic criteria
(6).
The treatment effects of groups A and B were
retrospectively analyzed. The antibacterial drugs employed in group
A were a combination of cefoperazone, sulbactam (Pfizer, NY, USA)
and tanreqing (Kangbao, Shanxi, China). Cefoperazone (2 g) and
sulbactam (3 g) were administered by intravenous drip every 8 h.
Tanreqing (20 ml) was then added into the intravenous drip once a
day. For group B, the cases were treated with only cefoperazone and
sulbactam. The curative effect and prognosis of the two groups were
recorded and the remaining treatments were administered as per
clinical routine. The effects were evaluated based on the guiding
principles of clinical research on antibacterial agents, as
established released by the Ministry of Health (7). The main criteria for the clinical
effects were symptom, sign and laboratory inspection. The 4 grades
for assessment were: recovery, significantly improved, improved and
no response. In addition, mortality within 28 days after infection
was observed.
Statistical analysis
Enumeration data were carried out using the
χ2 test for statistical analysis. P<0.05 was
considered to indicate a statistically significant difference.
Results
Treatment effects
Table I shows the
outcomes for the two different drug treatments for Acinetobacter
baumannii. For the sulperazone and tanreqing group, there were
8 recovered patients, 6 patients with significant effects, 3
patients with some improvement and 1 case with no response. In
addition one patient succumbed after 28 days. By contrast, in the
sulperazone-treated group there were 4 patients who were
successfully treated, 3 patients with significant effects, 2
patients with some improvement and 2 patients with no response.
Four patients succumbed after 28 days.
 | Table I.Comparison of treatment effects in the
two groups. |
Table I.
Comparison of treatment effects in the
two groups.
| Group | Cases | Clinical
efficiency | Mortality in 28
days | P-value |
|---|
| Sulperazone +
tanreqing | 15 | 68.4% | 6.66% | <0.05 |
| Sulperazone | 15 | 45.0% | 26.66% | <0.05 |
Comparison of the disappearing time of
clinical symptoms between the two groups
After relieving the fever, the time period in which
cough, phlegm, asthma, pulmonary rales and pulmonary shadow
disappeared were compared between the two groups. Significant
differences were identified (P<0.05, Table II).
| Table II.Comparison of the time period clinical
symptoms terminated between the two groups (day, mean ± standard
deviation). |
Table II.
Comparison of the time period clinical
symptoms terminated between the two groups (day, mean ± standard
deviation).
| Group | Patient no. | Fever relieving | Time cough, phlegm,
asthma terminated | Time pulmonary rales
terminated | Time shadow
terminated |
|---|
| Sulperazone +
tanreqing | 15 | 2.42±0.87 | 5.47±2.17 | 4.37±1.53 | 7.22±1.56 |
| Sulperazone | 15 | 2.92±1.02 | 7.13±3.03 | 6.05±1.86 | 8.69±2.25 |
Adverse reactions
None of the patients exhibited skin rash or other
allergic reactions during treatment. Liver and renal function, a
urine routine examination, and ECG showed no significant changes
prior to and following treatment.
Discussion
Since the establishment of the Xiangyang Hospital in
1992, we have observed the emergence of Acinetobacter
baumannii and currently there are infection cases of
pan-resistant Acinetobacter baumannii (8–10). The
challenge for treating pulmonary infection with pan-resistant
Acinetobacter baumannii involves selection of medication
(11). Previous findings have shown
that cefoperazone sodium and sulbactam sodium, as well as
minocycline and polymyxin are effective in terms of treating
pan-resistant Acinetobacter baumannii (12–15).
However, since polymyxin is no longer available, cefoperazone
sodium and sulbactam sodium tanreqing were used in the present
study to compare the effectiveness of the combination of the two
drugs (16).
Drug resistance arises in pan-resistant
Acinetobacter baumannii from several mechanisms, the most
important of which are the production of many types of hydrolases,
changing the affinity of antibiotics and penicillin-binding protein
(PBP), and decreasing the permeability of the outer membrane of
bacteria or active efflux. Thus, the production of many types of
hydrolases has become the main resistance mechanism.
Sulbactam inhibits many different types of
β-lactamases (TEM1, TEM2 and SHV1) and most extended spectrum of
β-lactamases are produced by bacteria in order to manage many
bacteria resistant to hydrolase (17,18). It
can have direct effects on PBP2 of bacteria and can enhance the
sensitivity by 60–100%. There is also a direct correlation between
its bacteriostasis and drug concentration. Cefoperazone and
sulbactam have synergistic effects on 61% of the acinetobacter
bacterial strain and have additive effects on 39% of acinetobacter
bacterial strain, which can fully present its unique bactericidal
effects on acinetobacter (19).
As an efficient, low toxicity and safe new
traditional Chinese medicine, tanreqing is composed of radix
scutellariae, bear bile powder, cornu gorais, honeysuckle and
fructus forsythiae and has beneficial roles for clearing heat,
detoxicating and resolving phlegm. The honeysuckle and fructus
forsythiae in tanreqing can inhibit and disinfect many pathogenic
microorganisms, as well as increase the anti-inflammatory effects
of neutrophil and macrophage. This improves the content of serum
lytic enzyme and enhances the immune mechanism (20–22).
Furthermore, tanreqing improves Th1- and Th2-cell function and
promotes the immunity of body cells and fluids. Moreover, tanreqing
has significant inhibitory effects on the increase of centric fever
medium prostaglandin E2 and cyclic adenosine monophosphate and
hypersensitivity process of immune cells (23,24).
Tanreqing has bacteriostasis effects on 10 common bacteria such as
Staphylococcus aureus, Staphylococcus epidermidis,
β-hemolytic Streptococcus, Haemophilus influenzae,
Pseudomonas aeruginosa, Escherichia coli,
Proteusbacillus vulgaris, K. pneamoniae,
Mycoplasma and mycobacterium tuberculosis. In
addition, tanreqing lowers the mortality of mice infected by
Staphylococcus aureus and influenza virus (25).
In summary, the results have shown that sulperazone
in combination with tanreqing is more effective in controlling
pan-resistant Acinetobacter baumannii. The combined therapy
of sulperazone and tanreqing has higher clinical efficiency (68.4%)
compared to the monotherapy of sulperazone (45%). Additionally, the
combination therapy enhances the survivability of infected patients
with 6.66% of mortality rate compared to 26.6% with sulperazone
alone. Thus, the combination therapy of sulperazone and tanreqing
is recommended in the regulation of Acinetobacter
baumannii-induced pan-resistance in hospitalized patients
undergoing critical care.
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