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pneumonia in older
outpatients with fever
Abstract
Objectives: To study the pathogenic bacterial profile and drug resistance in older patients
with community-acquired pneumonia (CAP) in outpatients with fever, and provide evidence to
diagnose and treat CAP timely and accurately.
Methods: We studied older (>60 years) patients with CAP in Beijing Shijitan Hospital from 2016
to 2017. Pathogenic bacteria from sputum of patients were isolated and identified and their
resistance to antibiotics was tested. Risk factors for multidrug-resistant CAP (MDR-CAP) and
clinical outcomes were analyzed.
Results: A total of 5563 outpatients with fever were recruited and 391 had CAP. A total of 117
isolates of pathogenic bacteria were obtained from 176 CAP cases. The main pathogenic bacteria
were Klebsiella pneumoniae (27.4%), Escherichia coli (17.9%), Staphylococcus aureus (12.0%),
Pseudomonas aeruginosa (10.3%), and Streptococcus pneumoniae (9.4%). A drug sensitivity test
(DST) showed that K. pneumoniae, E. coli, and P. aeruginosa had good sensitivity to imipenem,
cefoperazone/sulbactam, piperacillin/tazobactam, and amikacin. Staphylococcus aureus and
Streptococcus pneumoniae had strong sensitivity to vancomycin, linezolid, and levofloxacin.
Previous multiple antibiotic treatment was an independent risk factor for MDR-CAP.
Conclusions: Gram-negative bacteria are the main pathogenic bacteria in older patients with
CAP. Identification and DSTs of pathogens could enable accurate diagnosis and treatment of CAP.
1
Department of Infectious Diseases, Beijing Shijitan
Hospital, Capital Medical University, Haidian District, Corresponding author:
Beijing, China Zhongying Bao, Department of Infectious Diseases,
2
Department of Clinical Laboratory, Beijing Shijitan Beijing Shijitan Hospital, Capital Medical University, No.
Hospital, Capital Medical University; Beijing Key 10, Tie Yi Road, Yang Fang Dian, Haidian District, Beijing,
Laboratory of Urinary Cellular Molecular Diagnostics, 100038, China.
Haidian District, Beijing, China Email: bao66zhong@126.com
Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative
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attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
Luan et al. 4597
Keywords
Community-acquired pneumonia, drug sensitivity, older people, infection, antibiotics,
pathogenic bacteria
Date received: 25 January 2018; accepted: 24 May 2018
prepared from all specimens and examined using multivariate logistic regression.
for squamous epithelial cells and WBCs. Comparison between the targeted therapy
All smears were treated with gram stain and empiric therapy groups was performed
and examined via light microscopy. Under using the v2 test for categorical variables
a low-power field in microscopy, if the and the two-sample t-test for continuous
number of squamous epithelial cells variables. P < 0.05 indicated statistical sig-
was < 10, the WBC count was > 25, or the nificance for all statistical analyses.
number of squamous epithelial cells/WBCs
was less than 1/2.5, the specimens of Quality controls
sputum were considered to qualify for anal-
ysis. The specimens were re-collected if the Quality control of each batch test was
sputum did not meet these criteria. performed with the reference strains
Escherichia coli (ATCC 25922), Klebsiella
Isolation, identification, and DSTs of pathogenic pneumoniae (ATCC 700603), Pseudomonas
bacteria. The sputum collected from patients aeruginosa (ATCC 27853), and
was inoculated on a blood agar plate, choc- Staphylococcus aureus (ATCC 25923).
olate plate, and MacConkey plate, and cul-
tured at 35 C with 5% carbon dioxide for 18 Results
to 24 hours. Identification of pathogens and
the DST were carried out in a clinical micro- Characteristics of the patients
biology laboratory using the Vitek 2 system The study enrolled a total of 5563 outpa-
(bioMerieux, St. Louis, MO, USA). The tients with fever and 391 were diagnosed
Clinical and Laboratory Standards Institute with CAP. Among the patients, 176 were
document M100-S24 (2014) was used for older than 60 years old, 94 were men, and
interpretation of the DST.12 82 were women. The mean age of the
patients was 68.3 4.3 years.
Analysis of clinical outcomes
The treatment information of patients was Isolation and identification of pathogens
analyzed. Patients with pathogenic bacteria A total of 117 isolates of pathogens were
that were isolated from sputum were treated obtained from sputum specimens of 97/176
according to the results of the DST of patho- (55.1%) patients. Of all the isolates, 85/117
gens and were included in the targeted therapy (72.6%) were gram-negative bacteria, 27/117
group. Patients with no pathogenic bacteria (23.1%) were gram-positive bacteria, and
that were isolated from sputum were treated 5/117 (4.3%) were fungi. Additionally,
empirically and were included in the empiric 8/176 (4.5%) patients had more than one
therapy group. The alleviating time of clinical pathogen. The main pathogens identified
symptoms and the rate of hospitalization were were K. pneumoniae (32 strains, 27.4%),
compared between the two groups. E. coli (21 strains, 17.9%), P. aeruginosa
(12 strains, 10.3%), Staphylococcus aureus
Statistical analysis (14 strains, 12.0%), and Streptococcus pneu-
moniae (11 strains, 9.4%) (Table 1).
Univariate analysis of all potential risk fac-
tors for MDR-CAP was performed using
SPSS 19.0 (Armonk, NY, USA). Variables DST of the pathogens
with significant differences between two Gram-negative bacteria: Levofloxacin, imipen-
groups in univariate analysis were analyzed em, ceftazidime, cefoperazone/sulbactam,
Luan et al. 4599
Table 2. Drug susceptibility of major gram-negative bacteria to commonly used antibacterial agents.
Klebsiella pneumoniae Escherichia coli Pseudomonas aeruginosa
(n ¼ 32) (n ¼ 21) (n ¼ 14)
Antibacterial
agents S I R S I R S I R
Values are n (%). S: susceptible; I: intermediate; R: resistance; ESBL: extended-spectrum beta-lactamase; : not tested;
SMZ-TMP: sulfamethoxazole-trimethoprim.
4600 Journal of International Medical Research 46(11)
Gram-positive bacteria: The antimicrobi- 6.593; 95% CI: 2.366–18.373, P < 0.001),
al activity of amikacin, teicoplanin, vanco- previous episode of pneumonia (OR:
mycin, linezolid, and levofloxacin against 2.714; 95% CI: 1.098–6.712, P ¼ 0.045),
Staphylococcus aureus in cases of CAP and previous hospitalization (OR: 2.597;
was strong (sensitivity rate, 78.6%). 95% CI: 1.066–6.329, P ¼ 0.044). The risk
Penicillin, amoxicillin/clavulanate, azithro- factors in univariate analysis were included
mycin, erythromycin, vancomycin, linezo- in multivariate logistic regression analysis.
lid, clindamycin, and levofloxacin were Prior multiple antibiotic treatment was the
more effective against Streptococcus pneu- only independent risk factor for MDR-
moniae (sensitivity rate, 72.7%). The CAP (OR: 3.542; 95% CI: 1.141–14.827,
antimicrobial activity of sulfamethoxazole- P ¼ 0.002) (Table 4).
trimethoprim was also strong against
Staphylococcus aureus (sensitivity rate,
64.3%) and Streptococcus pneumoniae (sen- Analysis of clinical outcomes
sitivity rate, 63.6%) (Table 3).
In our study, 97 patients were included in
the targeted therapy group and 79 patients
Risk factors for MDR-CAP in the empiric therapy group. The alleviat-
A total of 29 MDR-CAP cases were identi- ing times of coughing, high fever, and lung
fied in this study. Univariate analysis rales in the targeted therapy group were sig-
showed that MDR-CAP was significantly nificantly shorter than those in the empiric
associated with age 75 years (odds ratio therapy group (t ¼ 4.422, 7.862, and 6.848,
[OR]: 2.643; 95% confidence interval [CI]: all P < 0.05). The rate of hospitalization in
1.080–6.472, P ¼ 0.045), comorbidities (OR: the targeted therapy group was significantly
3.986; 95% CI: 1.544–10.288, P ¼ 0.004), lower than that in the empiric therapy
prior multiple antibiotic treatment (OR: group (v2 ¼ 4.262, P < 0.05) (Table 5).
Table 3. Drug susceptibility of major gram-positive bacteria to commonly used antibacterial agents.
Antibacterial agents S I R S I R
Non-MDR MDR
(n ¼ 68), (n ¼ 29), OR
Risk factors n (%) n (%) OR (95% CI) P value (95% CI) P value
by people outside the hospital when they feel and levofloxacin (sensitivity rate, 72.7%).
slightly uncomfortable. Additionally, some However, Liu et al.15 and Yang et al.20
primary community doctors lack the profes- showed that, in macrolides, antibiotics and
sional knowledge to choose antibiotics ratio- clindamycin had low activity against
nally, and cause overuse of antibiotics, Streptococcus pneumoniae strains in pulmo-
especially penicillins and cephalosporins.16 nary infection (resistance rate, >75.0%).
This may be the reason why more gram- This difference in sensitivity among studies
negative bacteria are isolated than gram- may be related to the smaller sample size in
positive bacteria. The growth conditions of this study and less use of these two types of
H. influenzae and Streptococcus pneumoniae antibiotics in clinics in this region. We also
are more demanding in vitro, which may found 29 MDR-CAP cases in this study and
also be the cause of their low detection. these cases were associated with prior
Our study showed that resistance of multiple antibiotic treatment. Although
K. pneumoniae to cefuroxime, piperacillin, use of multiple antibiotics might significant-
and ampicillin was high. The sensitivity of ly inhibit bacterial growth, it also might
E. coli to antibiotics was low, including lead to frequent bacterial mutation and
cephalosporins, levofloxacin, and ampicil- drug resistance. When more than one anti-
lin. However, the resistance of the main microbial agent is present in the microor-
gram-negative bacteria to carbapenems, ganism environment, pressure from these
aminoglycosides, and b-lactamase inhibitor antimicrobial agents results in selection
complex was low, which is similar to the of bacteria using multiple or polyvalent
studies of Xie et al.17 and Liu et al.18 in resistance mechanisms. Therefore, bacteria
China. Resistance of the main gram- optimize one resistance mechanism to sur-
negative bacteria to cephalosporins in our vive in variable environments or increase
study was high, which may be related to mutational events during situations of
their widespread use. Although the sensitiv- bacterial stress.21,22
ity of the major gram-negative bacteria to Analysis of clinical outcomes showed
amikacin was high, amikacin has a higher that the clinicians’ targeted therapy accord-
toxicity to the kidney and poor activity ing to results of identification and DST of
against some drug-resistant strains. pathogenic bacteria could significantly
Therefore, amikacin is not usually preferred shorten the alleviating time of clinical
for treating CAP. In the current study, the symptoms and hospitalization rate of
detection rate of E. coli-producing ESBLs patients. The results of identification and
was higher than that of K. pneumoniae-pro- DST of pathogenic bacteria can help clini-
ducing ESBLs. This finding could explain cians select optimal targeted antibiotics,
why the resistance of E. coli to antibiotics and can eliminate pathogenic bacteria.
was higher than that for K. pneumoniae Although current methods can isolate and
because ESBL production increases bacte- identify a pathogen from only 30% to 40%
rial resistance.19 of patients,23–25 analysis of the pathogenic
In our study, vancomycin, linezolid, bacterial profile and drug resistance in the
levofloxacin, amikacin, and teicoplanin region can help clinicians carry out reliable
had strong antimicrobial activity against empiric therapy protocols to treat patients
Staphylococcus aureus (sensitivity rate, with no isolation of pathogenic bacteria.
78.6%). Streptococcus pneumoniae Our study was retrospective and the
showed high sensitivity to penicillin, amox- sample size was limited, with some possible
icillin/clavulanate, azithromycin, erythro- selection bias. However, our findings are
mycin, vancomycin, linezolid, clindamycin, still meaningful for providing a foundation
Luan et al. 4603