Bacteremia due to extended-spectrum-β-lactamase-producing Aeromonas spp. at a medical center in Southern Taiwan.
ABSTRACT Although extended-spectrum-β-lactamase (ESBL)-producing aeromonads have been increasingly reported in recent years, most of them were isolates from case reports or environmental isolates. To investigate the prevalence of ESBL producers among Aeromonas blood isolates and the genes encoding ESBLs, consecutive nonduplicate Aeromonas blood isolates collected at a medical center in southern Taiwan from March 2004 to December 2008 were studied. The ESBL phenotypes were examined by clavulanate combination disk test and the cefepime-clavulanate ESBL Etest. The presence of ESBL-encoding genes, including bla(TEM), bla(PER), bla(CTX-M), and bla(SHV) genes, was evaluated by PCR and sequence analysis. The results showed that 4 (2.6%) of 156 Aeromonas blood isolates, 1 Aeromonas hydrophila isolate and 3 Aeromonas caviae isolates, expressed an ESBL-producing phenotype. The ESBL gene in two A. caviae isolates was bla(PER-3), which was located in both chromosomes and plasmids, as demonstrated by Southern hybridization. Of four patients with ESBL-producing Aeromonas bacteremia, two presented with catheter-related phlebitis and the other two with primary bacteremia. Three patients had been treated with initial noncarbapenem β-lactams for 5 to 10 days, and all survived. In conclusion, ESBL producers exist among Aeromonas blood isolates, and clinical suspicion of ESBL production should be raised in treating infections due to cefotaxime-resistant Aeromonas isolates.
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ABSTRACT: Salmonella spp. infections are considered as the most common food-borne disease globally. The contamination of food products with Salmonella has given rise to severe health and economic challenges. This study assessed the prevalence of Salmonella in the faeces of cows and goats in the Eastern Cape province of South Africa, their antibiotic resistance patterns as well as antibiotic-resistant gene determinant. Antibiotic disc was used for antibiogram profiles while polymerase chain reaction was employed for the detection of antibiotic-resistant genes. A total of 150 Salmonella were isolated from the faecal samples. Eighty two (55 %) isolates were recovered from cow faeces while 68 (45 %) were isolated from goat faeces. All Salmonella isolates were sensitive to ciprofloxacin (100 %) while 95 % were sensitive to ofloxacin. Also, a high sensitivity of 93 and 89 % was observed against nalidixic acid and ofloxacin, respectively. Salmonella isolates demonstrated moderate sensitivity against cephalothin (70 %), chloramphenicol (75 %) and minocycline (68 %) while 49 % were resistant to tetracycline and erythromycin. The prevalence of the antibiotic-resistant genes in Salmonella isolates were detected as follows: integron conserved segment 28 % (42/150), bla TEM gene 19.3 % (29/150), bla pse1 7.3 % (11/150) and bla amp C 4.7 % (7/150). The results obtained in the study imply that cow and goat faeces could be potential reservoirs of Salmonella and could possibly cause infections as a result of contamination of food products. There is a need for a surveillance system to track resistance patterns of Salmonella circulating in South Africa.Tropical Animal Health and Production 10/2014; · 0.97 Impact Factor
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ABSTRACT: Aeromonas dhakensis, often phenotypically identified as A. hydrophila, is an important human pathogen. The present study aimed to compare the clinical and biological features of A. dhakensis and A. hydrophila isolates from human wounds. A total of 80 of Aeromonas wound isolates collected between January 2004 and April 2011 were analyzed. The species was identified by the DNA sequence matching of rpoD and gyrB (or rpoB if necessary). Most of the Aeromonas isolates were identified as A. dhakensis (37, 46.3%), and 13 (16.3%) as A. hydrophila. Both these two species alone can cause severe skin and soft-tissue infections. More A. dhakensis isolates were found in wounds exposed to environmental water (32.4% vs. 0%, P=0.042). More biofilm formation was noted among A. dhakensis isolates (mean OD570 , 1.23±0.09 vs. 0.78±0.21, P=0.03). The minimal inhibitory concentrations of ceftriaxone, imipenem, and gentamicin for A. dhakensis isolates were higher (P values <0.0001, 0.04, and 0.01, respectively). The survival rates of Caenorhabditis elegans co-incubated by A. dhakensis from day 1 to day 3 were lower than those of worms infected with A. hydrophila in liquid toxicity assays (all P values <0.01). A. dhakensis isolates exhibited more cytotoxicity, as measured by the released leukocyte lactate dehydrogenase levels in human normal skin fibroblast cell lines (29.6±1.2% vs. 20.6±0.6%, P<0.0001). The cytotoxin gene ast was primarily present in A. hydrophila isolates (100% vs. 2.7%, P<0.0001). In summary, A. dhakensis is the predominant species among Aeromonas wound isolates, and more virulent than A. hydrophila. This article is protected by copyright. All rights reserved.Clinical Microbiology and Infection 11/2013; · 4.58 Impact Factor
- Infection, genetics and evolution: journal of molecular epidemiology and evolutionary genetics in infectious diseases 04/2014; · 3.22 Impact Factor
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Dec. 2011, p. 5813–5818
Copyright © 2011, American Society for Microbiology. All Rights Reserved.
Vol. 55, No. 12
Bacteremia Due to Extended-Spectrum-?-Lactamase-Producing
Aeromonas spp. at a Medical Center in Southern Taiwan?
Chi-Jung Wu,1,2,5Yin-Ching Chuang,6,7Mei-Feng Lee,6Chin-Chi Lee,1,2,4Hsin-Chun Lee,2,4
Nan-Yao Lee,2,4Chia-Ming Chang,2,4Po-Lin Chen,1,2Yu-Tzu Lin,5
Jing-Jou Yan,3and Wen-Chien Ko2,4*
Departments of Graduate Institute of Clinical Medicine,1Internal Medicine,2and Pathology,3and Center for Infection Control,4
National Cheng Kung University Medical College and Hospital, Tainan, Taiwan; National Institute of Infectious Diseases and
Vaccinology, National Health Research Institutes, Miaoli, Taiwan5; Department of Medical Research,
Chi Mei Medical Center, Tainan, Taiwan6; and Department of Internal Medicine,
Chi Mei Medical Center, Liou Ying, Tainan, Taiwan7
Received 6 May 2011/Returned for modification 6 September 2011/Accepted 27 September 2011
Although extended-spectrum-?-lactamase (ESBL)-producing aeromonads have been increasingly reported
in recent years, most of them were isolates from case reports or environmental isolates. To investigate the
prevalence of ESBL producers among Aeromonas blood isolates and the genes encoding ESBLs, consecutive
nonduplicate Aeromonas blood isolates collected at a medical center in southern Taiwan from March 2004 to
December 2008 were studied. The ESBL phenotypes were examined by clavulanate combination disk test and
the cefepime-clavulanate ESBL Etest. The presence of ESBL-encoding genes, including blaTEM, blaPER,
blaCTX-M, and blaSHVgenes, was evaluated by PCR and sequence analysis. The results showed that 4 (2.6%) of
156 Aeromonas blood isolates, 1 Aeromonas hydrophila isolate and 3 Aeromonas caviae isolates, expressed an
ESBL-producing phenotype. The ESBL gene in two A. caviae isolates was blaPER-3, which was located in both
chromosomes and plasmids, as demonstrated by Southern hybridization. Of four patients with ESBL-produc-
ing Aeromonas bacteremia, two presented with catheter-related phlebitis and the other two with primary
bacteremia. Three patients had been treated with initial noncarbapenem ?-lactams for 5 to 10 days, and all
survived. In conclusion, ESBL producers exist among Aeromonas blood isolates, and clinical suspicion of ESBL
production should be raised in treating infections due to cefotaxime-resistant Aeromonas isolates.
Aeromonads, oxidase-producing Gram-negative rods, are
aquatic microorganisms and have been implicated in a variety
of human diseases (11). Three well-known principal classes of
?-lactamases recognized in aeromonads are class C cepha-
losporinases, class D penicillinases, and class B metallo-?-lac-
tamases (MBL) (11), whereas production of extended-spec-
trum ?-lactamases (ESBLs) has received little attention.
ESBLs belong to the class A ?-lactamases according to Am-
bler’s classification (1a). They confer resistance to all penicil-
lins, older and newer cephalosporins, and monobactams but
not to cephamycins or carbapenems, and they are inactivated
by ?-lactamase inhibitors such as clavulanate. ESBL-producing
aeromonads have been increasingly reported in recent years.
The earliest report of a clinical case, in 2003, described a fecal
A. caviae strain harboring ESBL blaTEM-24from an aged pa-
tient with intestinal ischemia (16). Later on, ESBL-producing
environmental isolates were reported, including isolates carry-
ing blaPER-1from sludge in Switzerland (24), isolates carrying
blaPER-1, blaPER-6, blaSHV-12, blaVEB-1a, blaTLA-2, or blaGES-7
from the Seine River (8, 15), and Aeromonas hydrophila iso-
lates from an urban river in China (15). However, no study
focused on the prevalence and clinical manifestations of infec-
tions caused by ESBL-producing aeromonads. The aim of this
study was to investigate the prevalence of ESBL producers
among Aeromonas blood isolates, to investigate the genes en-
coding ESBLs, and to describe the clinical features of infected
patients. A literature review in search of clinical cases was also
conducted, with the hope of better understanding the current
status of ESBLs among clinical Aeromonas isolates.
MATERIALS AND METHODS
Bacterial isolates. Aeromonas blood isolates identified in the clinical microbi-
ology laboratory of National Cheng Kung University Hospital (NCKUH), a
university-affiliated medical center in southern Taiwan, from March 2004 to
December 2008 were collected and stored at ?70°C until use. For each patient,
if multiple isolates of the same species with identical antimicrobial susceptibility
profiles were obtained, only the first was taken into account. The genus Aero-
monas was identified by the positive oxidase test, fermentation of D-glucose,
motility, the absence of growth in 6.5% sodium chloride, and resistance to the
vibriostatic agent O/129 (150 ?g), and the identification was confirmed by the
API 20E system (BioMe ´rieux, Marcy-l’Etoile, France). Identification of Aero-
monas species was based on the sequence analysis of the partial rpoB gene by
PCR with the primers Pasrpob-L (5?-GCAGTGAAAGARTTCTTTGGTTC-3?)
and Rpob-R (5? GTTGCATGTTNGNACCCAT 3?) under the conditions pre-
viously described (12). The sequences of amplified DNA products were com-
pared with reference sequences available at the GenBank database using a
BLAST search (http://www.ncbi.nlm.nih.gov/BLAST/).
Antimicrobial susceptibility tests. The ESBL phenotype was examined by tests
proposed for the detection of ESBLs in Enterobacteriaceae by the Clinical and
Laboratory Standards Institute (CLSI) (3). Aeromonas isolates that demon-
strated a diameter of inhibition zone of ceftazidime (30 ?g) of ?22 mm or of
cefotaxime (30 ?g) of ?27 mm by the disk diffusion method—i.e., reduced
susceptibility to expanded-spectrum cephalosporins—were examined by a phe-
notypic confirmatory test, i.e. the ceftazidime-clavulanate and cefotaxime-clavu-
lanate combination disk test (CDT), and the cefepime-clavulanate ESBL Etest
(AB Biodisk, Solna, Sweden). The presence of ESBL was determined by a
* Corresponding author. Mailing address: Department of Internal
Medicine, National Cheng Kung University Hospital, No. 138, Sheng
Li Road 704 Tainan, Taiwan. Phone: 886-6-2353535 ext. 3596. Fax:
886-6-2752038. E-mail: email@example.com.
?Published ahead of print on 3 October 2011.
?5-mm increase in zone diameters for ceftazidime/clavulanate, cefotaxime/cla-
vulanate, or cefepime/clavulanate compared with those for ceftazidime, cefo-
taxime, or cefepime alone by CDT. Either a cefepime MIC reduction by ?3
2-fold dilutions with clavulanate or a rounded phantom inhibition zone below the
cefepime gradients with no ellipse visible around the cefepime end was also
indicative of the presence of ESBL activity (30). The MICs of doxycycline,
imipenem, ertapenem, piperacillin-tazobactam, cefotaxime, ceftazidime, and
levofloxacin for ESBL-producing isolates were determined by Etest, and the
results were interpreted following CLSI recommendations for A. hydrophila
complex (4). Genetic relatedness of ESBL producers of the same species was
examined by arbitrarily primed PCR with primers ERIC-1R (5?-ATGTAAGCT
CCTGGGGATTCAC-3?) and ERIC-2R (5?-AGTAAGTGACTGGGGTGAGC
Detection of ESBL genes by PCR. For all phenotypically confirmed ESBL-
producing Aeromonas isolates, PCR amplification, cloning, and DNA sequence
analyses were conducted to determine the ESBL genotypes, including blaTEM,
blaPER, blaCTX-M, and blaSHVgenes, as well as the presence of the MBL blaCphA
gene and the AmpC ?-lactamase blaMOXgene by using previously described
PCR primers and conditions (5, 17–19, 28, 34) (Table 1). The sequences of
amplified DNA products were compared with the GenBank database to identify
the types of ?-lactamase genes.
Localization of the blaPER-3gene. The location of the blaPER-3gene was
analyzed by using the S1 nuclease technique as described previously (22). South-
ern hybridization was performed with a digoxigenin (DIG)-labeled blaPER-3gene
specific probe, obtained by PCR amplification with the primers PER-A(F) and
PER-R1 (5?-CTCGTCTCCCTGATACGCTTTC-3?) using a DIG system (DIG
DNA labeling and detection kit; Roche Diagnostics, Germany) according to the
manufacturer’s instructions (29).
Patients and literature review. Medical records of patients with ESBL-pro-
ducing Aeromonas bacteremia were reviewed to collect the clinical data. The
severity of acute illness at the onset of Aeromonas bacteremia was assessed within
1 day after admission by the Pittsburgh bacteremia score, a previously validated
scoring system that was based on mental status, body temperature, blood pres-
sure, requirement for mechanical ventilation, and recent cardiac arrest (2).
Critical illness was defined as a Pittsburgh bacteremia score of ?4 points. An
English-language literature review was also conducted to find clinical cases of
patients with ESBL-producing Aeromonas infections by querying the PubMed
database between April 1993 and April 2011 with the keywords “Aeromonas” and
Isolates with the ESBL phenotype. During the study period,
156 consecutive nonduplicate Aeromonas blood isolates were
collected. Fifty-five (35%) Aeromonas blood isolates with
reduced susceptibility to expanded-spectrum cephalosporins
were examined for the ESBL phenotype by the CDT and
ESBL Etest. By CDT with ceftazidime, cefotaxime, and
cefepime with and without clavulanate, a ?5-mm increase in
zone diameter was demonstrated in isolates of A. hydrophila
A2-970201 (from patient A), Aeromonas caviae A2-970915
(patient B), A. caviae A2-971106 (patient C), and A. caviae
A2-960104 (patient D). By ESBL Etest, the same four isolates
demonstrated a MIC reduction by ?3 2-fold dilutions with
clavulanate. Overall, four isolates (2.6%) of 156 blood isolates,
one A. hydrophila isolate and three A. caviae isolates, expressed
ESBL phenotypes. Arbitrarily primed PCR of three A. caviae
isolates showed three distinct gel patterns, suggestive of genet-
ically unrelated strains. By Etest, all four ESBL producers were
susceptible to imipenem, ertapenem, and levofloxacin and re-
sistant to cefotaxime and ceftazidime. Two isolates were sus-
ceptible to cefepime, and three were susceptible to piperacil-
lin-tazobactam. A profile of the antimicrobial susceptibility of
these isolates is shown in Table 2.
Detection of ESBL genes. Two A. caviae isolates, A2-970915
and A2-971106, carried the blaPERgene, which was 100%
(927/927 nucleotides) identical to the complete sequence of
the A. caviae ESBL blaPER-3gene (GenBank accession number
TABLE 1. PCR primers used to detect genes encoding ESBLs, MBL (blaCphA), and AmpC-?-lactamase (blaMOX)
among four ESBL-producing Aeromonas blood isolates
?-Lactamase(s) targeted Primer name Primer sequence (5?–3?)
blaCTX-Mgroup 1 (blaCTX-M-1,
blaCTX-Mgroup 2 (blaCTX-M-2)
blaCTX-Mgroup 9 (blaCTX-M-9,
5814WU ET AL.ANTIMICROB. AGENTS CHEMOTHER.
AY740681). Three isolates, A2-970201, A2-970915, and A2-
971106, possessed the blaTEM-116gene, with 99.2% to 100%
identity to the A. hydrophila blaTEM-116gene (GenBank acces-
sion no. FJ767900). None of the four ESBL-producing isolates
had blaCTX-Mor blaSHVgenes. The genes responsible for the
ESBL phenotype in isolates A2-970201 and A2-960104 were
Other genes encoding ?-lactamases, including the blaCphA
gene in A. hydrophila A2-970201 and the blaMOX-6-like gene
(96% to 99% identical to A. caviae blaMOX-6; GenBank acces-
sion no. GQ152601) in A. hydrophila A2-970201, A. caviae
A2-971106, and A. caviae A2-960104, were found (Table 2).
Localization of the blaPER-3gene. The result of Southern
hybridization for determining the localization of blaPER-3gene
in two A. caviae isolates demonstrated that the blaPER-3gene
was localized on both chromosomes and plasmids of these two
isolates (Fig. 1).
Patients and literature review. Clinical details of four pa-
tients with ESBL-producing Aeromonas bacteremia are shown
in Table 3. They developed Aeromonas bacteremia at 5 to 19
days after admission, and three (patients B, C, and D) did not
receive antibiotics in the preceding 1 month. Two patients
presented with catheter-related phlebitis, and two patients with
cancers of the digestive tract presented with primary bactere-
mia; the Pittsburgh bacteremia scores of all four patients were
less than 4. Three patients (B, C, and D) had been empirically
treated with penicillin derivatives or cephalosporin for 5 to 10
days, and all four survived for at least 2 weeks after the onset
A literature review found four clinical cases, including a
pediatric patient with A. hydrophila sepsis and pneumonia (26),
an aged patient with necrotizing fasciitis caused by an A. hy-
drophila isolate harboring blaTEM-24(7), an aged patient with
intestinal ischemia with a fecal isolate of A. caviae harboring
blaTEM-24(16), and an aged patient with pneumonia caused by
an A. caviae isolate harboring blaCTX-M-3(35) (Table 3).
Among three published cases with known clinical courses, the
clinical conditions of two patients with pneumonia and one
patient with necrotizing fasciitis deteriorated with initial non-
carbapenem antimicrobial therapy.
To date, though there is no standard method for detection of
ESBLs among aeromonads, most studies have adopted clavu-
lanate-based synergy tests (7, 26), such as those recommended
for phenotypic confirmation of ESBL-producing Enterobacte-
riaceae by CLSI (3). However, using expanded-spectrum ceph-
alosporins as ESBL substrates, antagonism by clavulanate on
ESBL may be masked by the coexistence of AmpC ?-lactama-
ses. Aeromonas hydrophila and A. caviae isolates have been
reported to possess chromosomal AmpC ?-lactamase genes
(11), as noted in our three isolates. Therefore, the synergy test
with cefepime, a novel cephalosporin not hydrolyzed by AmpC
TABLE 2. Profiles of antimicrobial susceptibility and the genes encoding ESBLs, MBL, and AmpC ?-lactamases
in ESBL-producing Aeromonas blood isolates
Disk diffusion, zone diam (mm)
MIC by Etest (?g/ml)
Detection of genes with specific primers
MBL gene, blaCphA
AmpC ?-lactamase gene, blaMOX
a?, increase of zone diameter (mm).
bS, susceptible; I, intermediate; R, resistant.
cKlebsiella pneumoniae ATCC 700603 harboring the blaSHV-18gene was used as a quality control strain.
dThe blaTEM-116gene, whose product is not an ESBL, was found.
eTwo clinical strains of K. pneumoniae harboring the blaCTM- 9gene and the blaCTM-13gene were used as quality control strains.
VOL. 55, 2011EXTENDED-SPECTRUM-?-LACTAMASE-PRODUCING AEROMONAS SPP.5815
?-lactamases, was also applied in this study. The results of
different methods for detection of the ESBL phenotype—i.e.,
CDT using ceftazidime, cefotaxime, and cefepime with and
without clavulanate and the cefepime-clavulanate ESBL
Etest—were concordant, with all detecting the same four
ESBL producers. However, the limited number of ESBL iso-
lates in this study makes it uncertain that the performance of a
ceftazidime- or cefotaxime-based combination disk method
would be identical to that of the cefepime-based synergy test.
Although more investigations are warranted, the cefepime-
based synergy test may be helpful in screening the ESBL phe-
notype among aeromonads carrying AmpC ?-lactamases.
Among four ESBL producers, two A. caviae isolates and one
A. hydrophila isolate harbored the blaTEM-116gene. Studies
demonstrated that none of the environmental Aeromonas iso-
lates (1) or clinical Klebsiella pneumoniae isolates carrying the
blaTEM-116gene expressed ESBL phenotypes (14), and there-
fore the blaTEM-116gene is not thought to be associated with
ESBL activity. The blaPER-3gene was first identified in an A.
caviae isolate in France and was found to be located within the
class 1 integron In39 (31). Its product is the ESBL PER-3, and
it is considered to be responsible for the ESBL activity in two
A. caviae isolates in the present study. We further demon-
strated that the blaPER-3gene was located in both chromosome
and plasmids of the two isolates. So far, this is the second
report of blaPER-3ESBL among aeromonads in the literature.
The original acquisition of the blaPER-3gene in A. caviae is
FIG. 1. The localization of the blaPER-3gene was determined by
genomic mapping with S1 nuclease digestion by pulsed-field gel elec-
trophoresis (A) and hybridizations with probes for the blaPER-3gene
(B). The genomic DNA of A. caviae A2-970915 and A. caviae A2-
971106 was undigested (lanes 1 and 5) or was digested with S1 nuclease
(lanes 2 and 4). Lane 3, Lambda ladder PFG marker (New England
BioLabs). 4, linearized chromosomes; ?, plasmids.
TABLE 3. Clinical features of patients with ESBL-producing Aeromonas infections in the present study and the literature
at 2 weeks
Post-lumbar spine surgery for
Hospital, probably phlebitis
NA, due to hospital
Tongue cancer with lung
Hospital, unknown route
TZP (d1-5), IPM (d6-10)
Hospital, unknown route
AMC (d1-3), CTX (d4-7),
Hospital, probably phlebitis
FEP (d1-3), CAZ (d4-10),
Reported in the literature
Disease progressed with
AMC, CRO, MET
Bacteremia, pneumonia Community, ingestion of
Disease progressed with
CTX, OXA, VAN,
SAM, and KLA,
improved with IPM
CPZ, CIP (d1-5), IMP
aAbbreviations of antibiotics: IPM, imipenem; AMC, amoxicilin/clavulanate; CTX, cefotaxime; ETP, ertapenem; CAZ, ceftazidime; LVX, levofloxacin; TZP, piperacillin-tazobactam; CIP, ciprofloxacin; CPZ,
cefoperazone; MET, metronidazole; FEP, cefepime; CRO, ceftriaxone; OXA, oxacillin; VAN, vancomycin; KLA, clarithromycin. NA, not available. d, days. D1 was defined as the day of bacteremia onset. “D1-5”
represented the period from the day of bacteremia onset to the fifth day after bacteremia onset.
bAge in years; F, female; M, male.
cCo-pathogens isolated from blood: Escherichia coli, Acinetobacter baumannii, Enterococcus faecium, Streptococcus angiosus, coagulase-negative staphylococci.
dNA, not available.
5816 WU ET AL.ANTIMICROB. AGENTS CHEMOTHER.
undefined, but the blaPER-3gene is closely related to the bla-
PER-1gene, with 99% identity (9). Although ESBLs of the PER
type were not the most common ESBLs identified, the spread
of Enterobacteriaceae carrying the PER-1 ESBL gene as a chro-
mosomal insert has been recently reported in Europe (23).
Emergence of blaPER-1ESBLs was also noted among ESBL-
producing Acinetobacter baumannii and Pseudomonas aerugi-
nosa isolates in Europe and Asia (6, 32). Further, the horizon-
tal transfer of mobile genetic elements, such as plasmids and
integrons, was found to be attributable to an increasing inci-
dence of multidrug resistance among environmental Aeromo-
nas isolates (10). Therefore, it is possible that the blaPERgene
was horizontally transferred by mobile genetic elements be-
tween aeromonads and coexistent waterborne bacteria in
aquatic environments or between coexistent flora or pathogens
in human beings.
As with Aeromonas infections described previously (11, 33),
the clinical spectrum of patients with ESBL-producing Aero-
monas infections in the present study and the literature in-
cluded primary bacteremia, catheter-related infections, necro-
tizing fasciitis, pneumonia,
infections occurred in both community and nosocomial set-
tings. It is generally believed that patients acquire aeromonads
from oral consumption of or direct mucocutaneous contact
with contaminated water or seafood (11), whereas the risk
factors associated with acquisition of ESBL-producing Aero-
monas infections are not known due to their rarity. Prior ad-
ministration of antibiotics is one of the well-known risk factors
for infections caused by other ESBL-producing Enterobacteri-
aceae (20). However, most of our patients did not receive prior
antibiotics, which made the association of prior exposure of
antibiotics with development of ESBL-producing Aeromonas
infections not evident. Further clinical investigations involving
more patients are warranted to identify the risk factors for
ESBL-producing Aeromonas infections, as well as surveillance
of water from both hospitals and communities and suspicious
foods to explore the possible sources of infections.
Although clinical studies have shown that survival was better
with carbapenem treatment than with a cephalosporin among
patients with bacteremia caused by ESBL-producing K. pneu-
moniae or Enterobacter cloacae (13, 21), the optimal antimi-
crobial therapy for ESBL-producing Aeromonas infections is
not standardized. Among three published cases, the clinical
conditions of two patients with pneumonia and one patient
with necrotizing fasciitis deteriorated with initial noncarbap-
enem antimicrobial therapy (7, 26, 35). In contrast, our three
patients, not critically ill as defined by their Pittsburgh bacte-
remia scores, remained stable with empirical noncarbapenem
?-lactam agents, and all survived. The causes contributing to
the poor outcome of previously published cases were not
known. The difference in severity of illness at the time of
antibiotic initiation, carriage and expression of toxins of each
disease-causing aeromonad, or bacterial loads in clinical dis-
eases might be the possible reasons. Theoretically carbapen-
ems, not hydrolyzed by ESBLs, would work better than peni-
cillins or cephalosporins against ESBL producers. However,
antibacterial activity of carbapenems may be hampered by the
production of blaCphAMBLs in A. hydrophila, A. veronii, and A.
jandaei isolates, which is not easily detected by in vitro suscep-
tibility tests unless a large inoculum is used (27). It is too early
and gastroenteritis. These
to conclude the appropriateness of antimicrobial therapy from
the clinical experiences of limited cases. Perhaps to avoid the
complexity of ?-lactamase production in clinical Aeromonas
isolates, a fluoroquinolone could be the reasonable choice for
invasive Aeromonas infections.
In conclusion, of 156 Aeromonas blood isolates, 4 (2.6%)
exhibited the ESBL phenotype, and two A. caviae isolates
possessed the blaPER-3genes, which were located in both chro-
mosomes and plasmids. The complexity of ?-lactamase pro-
duction increases among clinical Aeromonas isolates, and clin-
ical use of ?-lactam agents for invasive Aeromonas infections
should be undertaken with caution.
This study was supported by grants from the National Science Coun-
cil, Taiwan (NSC 96-2628-B-006-004-MY3 and NSC 98-2320-B-006-
029), National Cheng Kung University Hospital, Tainan, Taiwan
(DOH100-TD-B-111-002), and National Health Research Institutes,
We thank Pei-Chen Wu for the laboratory work.
of Health,Executive Yuan
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