Epidemiological investigation of fluoroquinolone resistance in infections due to extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae.

The incidence of infections due to extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae (ESBL-EK) has increased markedly in recent years. Treatment is difficult because of frequent multidrug resistance. Although fluoroquinolones offer effective therapy for ESBL-EK infections, their usefulness is threatened by increasing fluoroquinolone resistance. To identify risk factors for fluoroquinolone resistance in ESBL-EK infections, a case-control study of all patients with ESBL-EK infections from 1 June 1997 through 30 September 1998 was conducted. Of 77 ESBL-EK infections, 43 (55.8%) were resistant to fluoroquinolones. Independent risk factors for fluoroquinolone resistance were fluoroquinolone use (odds ratio [OR], 11.20; 95% confidence interval [CI], 1.99-63.19), aminoglycoside use (OR, 5.83; 95% CI, 1.12-30.43), and long-term care facility residence (OR, 3.39; 95% CI, 1.06-10.83). The genotypes of fluoroquinolone-resistant ESBL-EK isolates were closely related. Efforts should be directed at modification of these risk factors to preserve the utility of fluoroquinolones in the treatment of ESBL-EK infections.     

Risk Factors of Nosocomial Infection with Extended-Spectrum Beta-Lactamase-Producing Bacteria in a Neonatal Intensive Care Unit in China

Abstract Background: To study risk factors of neonatal nosocomial infection caused by extended-spectrum beta-lactamase (ESBL)-producing bacteria in a neonatal intensive care unit (NICU). Patients and Methods: A retrospective cohort study was conducted in a university hospital NICU in south China. Medical records of neonatal nosocomial infection caused by Escherichia coli or Klebsiella pneumoniae were reviewed. Twenty-two neonates infected with ESBL-producing bacteria (case patients) were compared with 17 patients infected with non-ESBL producing strains (controls). Univariable and multivariable logistic regression were performed to analyze risk factors for infection with ESBL-producing strains. The spectrum of antimicrobial resistance of ESBL-positive E. coli or K. pneumoniae was also examined. Results: Both univariable and multivariable logistic regression analysis revealed that preterm low birth weight, prolonged mechanical ventilation (≥ 7 days) and prior use of third-generation cephalosporins were risks factors for ESBL-producing E. coli or K. pneumoniae infection (p < 0.05), with an odd ratio of 6.43 (95% CI: 1.51–27.44; p = 0.017), 7.50 (95% CI: 1.38–40.88; p = 0.017) and 9.00 (95% CI: 1.65–49.14; p = 0.008) respectively. However, the length of hospital stay before isolation of pathogens, endotracheal intubation, presence of a central venous catheter, days on third-generation cephalosporins and prior use of beta-lactamase inhibitors were not statistically significant (p > 0.05). Resistance of ESBL-positive strains to piperacillin, tobramycin, aztreonam and cephalosporins was significantly higher than that of ESBL-negative ones (p < 0.05). ESBL-producing strains appeared susceptible to carbapenem, fluoroquinolones, and beta-lactamase inhibitor combination piperacillin-tazobactam. Conclusions: Preterm low birth weight, prolonged mechanical ventilation and prior use of third-generation cephalosporins are risks factors for nosocomial infection with ESBL-producing bacteria in NICU.     

Epidemiology and risk factors for extended-spectrum beta-lactamase-producing organisms: a case control study at a tertiary care center in Lebanon

BACKGROUND: Infections caused by extended-spectrum beta-lactamase (ESBL)-producing gram-negative bacilli constitute a growing problem worldwide. At the American University of Beirut Medical Center (AUBMC), we have observed a significant rise in the rates of ESBL-producing organisms over the past 5 years. METHODS: Using a case control study design, we compared 99 patients with infections caused by ESBL-producing Escherichia coli and Klebsiella species and 99 frequency-matched controls from which ESBL-nonproducing isolates were recovered at AUBMC. RESULTS: The most notable risk factor for acquiring infections with ESBL-producing organisms was antibiotic consumption within 30 days of the infection (OR, 7.06; 95% CI: 3.27-15.24), with third-generation cephalosporins being associated with the highest risk (OR, 28.4; 95% CI: 3.7-215.8). Other risk factors included recent surgery, presence of a urinary catheter, and need for mechanical ventilation. Moreover, cases had a longer mean duration of hospitalization and were more likely to have relapse of their infection than controls. CONCLUSIONS: Recent antibiotic use is by far the most important predisposing factor to infection with ESBL-producing organisms. Such infections are associated with prolonged hospital stay and increased morbidity. Attention should be redirected toward the unjustified liberal use of broad-spectrum antibiotics both in the hospital and in the community.     

Fluoroquinolone resistance in pediatric bloodstream infections because of Escherichia coli and Klebsiella species

In pediatric bloodstream infections with fluoroquinolone (FQ)-resistant Escherichia coli and Klebsielia species, we noted an association between FQ resistance and extended-spectrum beta-lactamase (ESBL) production (OR, 12; 95% CI: 2.28-83.8). A case control study revealed no significant risk factors (including prior antibiotic use) for FQ resistance among ESBL E coli and Klebsiella species (ESBL-EK).     

Extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae: risk factors for infection and impact of resistance on outcomes.

The prevalence of antibiotic resistance among extended-spectrum beta-lactamase (ESBL)--producing Escherichia coli and Klebsiella pneumoniae has increased markedly in recent years. Thirty-three patients with infection due to ESBL-producing E. coli or K. pneumoniae (case patients) were compared with 66 matched controls. Total prior antibiotic use was the only independent risk factor for ESBL-producing E. coli or K. pneumoniae infection (odds ratio, 1.10; 95% confidence interval, 1.03--1.18; P=.006). Case patients were treated with an effective antibiotic a median of 72 hours after infection was suspected, compared with a median of 11.5 hours after infection was suspected for controls (P<.001). ESBL-producing E. coli or K. pneumoniae infection was associated with a significantly longer duration of hospital stay and greater hospital charges (P=.01 and P<.001, respectively). Finally, many ESBL-producing E. coli and K. pneumoniae isolates were closely related. ESBL-producing E. coli and K. pneumoniae infections have a significant impact on several important clinical outcomes, and efforts to control outbreaks of infection with ESBL-producing E. coli and K. pneumoniae should emphasize judicious use of all antibiotics as well as barrier precautions to reduce spread.     

Parallel analysis of individual and aggregated data on antibiotic exposure and resistance in gram-negative bacilli.

To evaluate the potential bias of analyzing aggregated data, we separately examined antibiotic exposure and resistance data for 35,423 patients admitted to a university hospital in Utah, from both an individual-patient perspective and group-level perspective. From 1994 through 1998, use of defined daily doses (per 1000 patient-days) of fluoroquinolones, third-generation cephalosporins, ampicillin-sulbactam, and imipenem increased by 82%, 38%, and 99%, and decreased by 38%, respectively, whereas group-level resistance rates of Enterobacteriaceae or Pseudomonas species changed only minimally. However, in individual-patient-level analyses performed by multivariable proportional hazards regression, exposure to a fluoroquinolone, third-generation cephalosporin, ampicillin-sulbactam, or imipenem was a strong risk factor for resistance to fluoroquinolones (adjusted hazard ratio [AHR], 4.0; P<.001), third-generation cephalosporins (AHR, 3.5; P<.001), ampicillin-sulbactam (AHR, 2.3; P=.008), or imipenem (AHR, 5.7; P<.001), respectively. Thus, group-level and individual-patient-level analyses of antibiotic-use-versus-susceptibility relations yielded divergent results. Multicenter studies should include individual-patient-level data to elucidate more fully the relation between antibiotic exposure and resistance.     

Surveillance of nalidixic acid-resistant and extended-spectrum beta-lactamase-producing Salmonella spp. isolated from human feces

Nalidixic acid (NA)-resistant and extended-spectrum beta-lactamase (ESBL)-producing Salmonella sp. isolates from human specimens are associated with clinical failure or delayed response in subjects treated with fluoroquinolone or third-generation cephalosporins. We studied drug susceptibility in 604 Salmonella enterica isolates from human feces in 2007. Of these, 39 (6.5%) were resistat to NA. Of these, 46% were resistant to two or more drugs and 2% susceptible to NA were resistant to multiple drugs (p < 0.001). Three ESBL-producing Salmonella sp. isolated were of the CTX-M family gene type. One strain of plasmid-mediated AmpC beta-lactamase belonged to the CMY-2 family gene type. Our results thus showed that NA-resistant isolates were resistant to antimicrobial agents and confirmed the presence of a small number of isolates producing ESBL and AmpC beta-lactamase.     

Bacteremia caused by Escherichia coli producing extended-spectrum beta-lactamase: a case-control study of risk factors and outcomes

A case-control study was conducted in order to identify the risk factors associated with bloodstream infection caused by Escherichia coli producing extended-spectrum beta-lactamase (ESBL) and to determine the outcomes of infected patients. Risk factors associated with ESBL production, according to univariate analysis, included a history of recent hospitalization [odds ratio (OR) 4.3, 95% confidence interval (CI) 2.1-8.9; p < 0.001], severe underlying diseases (OR 15, 95% CI 4.4-51.5; p < 0.001), prior exposure to urinary catheters (OR 8.3, 95% CI 3.2-21.7; p < 0.001) and nosocomial (OR 14.1, 95% CI 6.1-32.8; p < 0.001) or urinary (OR 3.6, 95% CI 1.7-7.4; p < 0.001) origin of the bacteria. Multivariate analysis revealed that severe underlying diseases (OR 31.2, 95% CI 6.7-144; p < 0.001) and nosocomial (OR 16.5, 95% CI 5.6-49; p < 0.001) and urinary origins (OR 7.8, 95% CI 2.6-23.8; p < 0.001) of the bacteria were independently associated with ESBL production in bacteremic E. coli. Crude mortality in case patients was more than twice as high as that in controls (p = 0.04). Production of ESBL increased the risk of inappropriate initial therapy (OR 95.6, 95% CI 27.4-334.2; p < 0.001). Treatment failed in 4/7 case patients treated with ceftazidime to which the isolate was susceptible in vitro. Our findings have implications for the choice of empirical therapy in nosocomial urinary tract infection.     

Consensus review of the epidemiology and appropriate antimicrobial therapy of complicated urinary tract infections in Asia-Pacific region

Urinary tract infections (UTIs) are among the most prevalent infectious diseases in the general population. They cause a substantial financial burden in the community and are associated with significant morbidity and mortality, particularly in hospitals. With increased rates of antimicrobial resistance, especially in the Asia-Pacific region, treatment of complicated UTIs (cUTIs) can be challenging for clinicians. Consideration of an optimal antimicrobial agent should be based on local resistance patterns, patient-specific factors, pharmacokinetic and pharmacodynamic principles, and cost. In the Asia-Pacific region, nearly half of Escherichia coli urinary isolates were resistant (including intermediate and resistant) to levofloxacin or ciprofloxacin and ≥30% were resistant to third-generation cephalosporins (cefotaxime, ceftriaxone, and ceftazidime) and cefepime. Overall, 33% of urinary E. coli isolates exhibited extended-spectrum β-lactamase (ESBL)-producing phenotypes. Prevalence of ESBL-producing urinary E. coli was highest in India (60%), followed by Hong Kong (48%) and Singapore (33%). All urinary isolates of E. coli were susceptible to both ertapenem and imipenem. All urinary isolates of Klebsiella pneumoniae were susceptible to imipenem and 4% of them were resistant to ertapenem. Care should be exercised when using trimethoprim-sulfamethoxazole (TMP-SMX), fluoroquinolones, and cephalosporins for the empirical treatment of UTIs, particularly cUTI among moderately to severely ill patients. Empiric antimicrobial treatment for serious cUTIs in which risk factors for resistant organisms exist should include broad-spectrum antibiotics such as carbapenems (ertapenem, imipenem, meropenem, and doripenem) and piperacillin-tazobactam. Aminoglycosides, tigecycline, and polymyxins (colistin or polymyxin B) can be used for the treatment of multidrug-resistant organisms or serious cUTIs when first-line options are deemed inappropriate or patients fail therapy. Because of considerable variability in different countries, local epidemiological data is critical in the effective management of UTIs in the Asia-Pacific region.     

Impact of a hospital-wide antimicrobial formulary intervention on the incidence of multidrug-resistant gram-negative bacteria

We examined the impact of an antimicrobial formulary change, based on reduction in third-generation cephalosporin use, on resistant gram-negative pathogens in a tertiary hospital. No significant changes were demonstrated in their incidence per 1000 patient-days. Otherwise, there was a significant decrease in rate of extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae (63.1% to 52.5%, P = .04) and third-generation cephalosporin-resistant Enterobacter species (31.4% to 25%, P = .04) between the 2 study periods. On the other hand, there was also a significant increase in rate of ampicillin-sulbactam-resistant Acinetobacter baumannii (8% to 47%, P = .01) after the implementation of the formulary intervention.     

Decreased susceptibility to commonly used antimicrobial agents in bacterial pathogens isolated from urinary tract infections in Rwanda: need for new antimicrobial guidelines

The aim of this study was to obtain data on susceptibility patterns of pathogens responsible for both community and hospital urinary tract infections (UTIs); and analyzed risk factors for infection caused by ciprofloxacin-resistant Escherichia coli and extended-spectrum β-lactamase (ESBL)-producing strains in Rwanda. Of 1,012 urine cultures prospectively studied, a total of 196 (19.3%) yielded significant growth of a single organism. The most common isolate (60.7%) was Escherichia coli. The antibiotics commonly used in UTIs are less effective except Fosfomycin-trometamol and imipinem. The use of ciprofloxacin in the previous 6 months (odds ratio [OR] = 7.59 [1.75-32.74]), use of other antibiotics in the previous 6 months (OR = 1.02 [1.02-2.34]), and production of ESBL (OR = 19.32 [2.62-142.16]) were found to be associated with ciprofloxacin resistance among the E. coli isolates. Risk factors for ESBL positivity were the use of ciprofloxacin and third-generation cephalosporin in the preceding 6 months (OR = 3.05 [1.42-6.58] and OR = 9.78 [2.71-35.25], respectively); and being an inpatient (OR = 2.27 [1.79-2.89]). Fosfomycin-trometamol could be included as a reasonable alternative for the therapy of uncomplicated UTI in Rwanda.     

Epidemiology of extended-spectrum beta-lactamase producing gram-negative bacilli at Siriraj Hospital, Thailand, 2003

A cross-sectional study was conducted from August to September, 2003 to determine the prevalence and risk factors in acquiring extended-spectrum beta-lactamase (ESBL) producing gram-negative bacilli (GNB) in patients admitted to Siriraj Hospital and the outcomes of these infections. Of 346 isolates of gram-negative bacteria in 249 patients, 102 isolates from 87 patients were colonization only, but 244 isolates from 162 patients were infections. The common GNB were Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii and Enterobacter cloacae. The overall prevalence of ESBL producers was 30.1%. K. pneumoniae had a very high prevalence of ESBL producers (56.9%). The urinary tract was the most common site for ESBL- producing GNB infections. Nosocomial infections, duration from admission to infection, peripheral line, urinary catheterization, nasogastric tube insertion and previous use of beta-lactams, cephalosporins and fluoroquinolones were associated with acquiring ESBL-producing GNB infections. ESBL-producing GNB were significantly more resistant to antimicrobial agents. More than 80% of ESBL-producing GNB were susceptible to carbapenems. Mortality in patients infected with ESBL-producing GNB (41.3%) was significantly higher than those infected with non- ESBL-producing GNB (19.8%).     

Valacyclovir provides optimum acyclovir exposure for prevention of cytomegalovirus and related outcomes after organ transplantation

A meta-analysis of 12 randomized trials (1574 patients) examined herpesvirus and related outcomes following organ transplantation over a range of acyclovir exposures (including valacyclovir). Overall, cytomegalovirus (CMV) infection (odds ratio [OR], 0.44; 95% confidence interval [CI], 0.34-0.57; P<.001), CMV disease (OR, 0.41; 95% CI, 0.31-0.54; P<.001), death (OR, 0.60; 95% CI, 0.40-0.90; P=.01), opportunistic infection (OR, 0.70; 95% CI, 0.53-0.91; P=.009), acute graft rejection (OR, 0.67; 95% CI, 0.52-0.86; P<.001), herpes simplex virus disease (OR, 0.17; 95% CI, 0.12-0.24; P<.001), and varicella-zoster virus disease (OR, 0.06; 95% CI, 0.01-0.25; P<.001) were significantly reduced. Increased acyclovir exposure influenced more end points: Maximum efficacy resulted from valacyclovir (8 g/day). Increasing acyclovir exposure to that achieved with valacyclovir extends benefits of prophylaxis to include impact on graft rejection and opportunistic infections.     

产超广谱β-内酰胺酶菌院内感染分析

目的：分析产超广谱β－内酰胺酶（ESBL）菌株引起的院内感染的临床特点。方法：收集北京协和医院1999年1－11月ESBL（＋）大肠杆菌和肺炎克菌白菌引起的院内感染50例,随机选择ESBL（－）病例45例作为对照。采用t检验和x^2检验进行分析。结果：住院时间及三代头孢菌素的使用是ESBL菌株感染的危险因素（P＜0．02）;ESBL（＋）组中腹腔、盆腔感染明显高于ESBL（－）组（P＜0．02）,其他感染在两组中无明显差别（P＞0．05）,致病菌分离后72h内选用敏感抗生素治疗组的预后明显好于72h内未选用敏感抗生素治疗组（P＜0．002）;的ESBL菌对亚胺培南敏感,对头孢美唑、阿米卡星和哌拉西林－他唑巴坦的耐药率低;头孢他啶对ESBL菌体外活性高,但临床疗效尚无定论。结论：ESBL菌院内感染病死率高,诊断明确后及时选用敏感抗生素可明显改善预后。     

哌拉西林-他唑巴坦替换第三代头孢菌素对肠道产超广谱β-内酰胺酶大肠埃希菌定植的影响

目的探讨哌拉西林．他唑巴坦替换第三代头孢菌素对肠道产超广谱β-内酰胺酶（ESBLs）大肠埃希茵定植的影响。方法研究为期9个月,分替换前期（Ⅰ期,3个月）和替换期（Ⅱ期,6个月）;Ⅱ期用哌拉西林．他唑巴坦替换第三代头孢菌素;收集Ⅰ期和Ⅱb期（Ⅱ期后3个月）入选患者临床资料,入院24h采集第一份直肠拭子（基线筛查）,并每7天或在出院前48h采集直肠拭子分离大肠埃希茵,双纸片法检测ESBLs;对至少进行过2次直肠拭子检查的患者（ES1人群）和ES1人群中在筛查或住院期间至少有1次未检出ESBLs的患者（ES2人群）分别分析产ESBLs大肠埃希茵获得率;采用非配对t检验、Pearson卡方检验和Fisher精确检验进行比较。结果Ⅱb期抗生素总用量（除哌拉西林-他唑巴坦）较Ⅰ期减少38．40％,第三代头孢菌素用量较Ⅰ期减少70．11％;哌拉西林-他唑巴坦用量增加895．35％;Ⅱb期ES1和ES2人群产ESBLs大肠埃希茵获得率明显低于Ⅰ期（11．4％比24．0％;11．8％比27．9％）。结论哌拉西林-他唑巴坦替换第三代头孢菌素可降低肠道产ESBLs大肠埃希茵定植。     

An observational study on bloodstream extended-spectrum beta-lactamase infection in critical care unit: incidence, risk factors and its impact on outcome

BackgroundThe incidence of nosocomial infections caused by extended-spectrum beta-lactamase (ESBL) producing microbes is increasing rapidly in the last few years. However, the clinical significance of infections caused by ESBL-producing bacteria in ICU patients remains unclear. We did a prospective study to look for incidence, risk factors and outcome of these infections in ICU patients.MethodsConsecutive isolates of Escherichia coli and Klebsiella pneumoniae in blood cultures were included for the analysis. Patients were divided into two groups based on the production of ESBL. Primary outcome measure was ICU mortality. Logistic regression analysis was done to identify risk factors for ESBL production.ResultsAmong the 95 isolates tested, 73 (76.8%) produced ESBL. Transfer from other hospitals or wards (OR 3.65; 95% CI: 1.3–10.1 and RR 1.35; 95% CI: 1.05–1.73) and previous history of antibiotics usage (OR 3.54; 95% CI: 1.04–11.97 and RR 1.5; 95% CI: 0.89–2.5) were risk factors for ESBL production. There was no significant difference in ICU mortality (p = 0.588), need for organ support between two groups.ConclusionThere is a high incidence of ESBL producing organisms causing blood stream infections in critically ill patients. Transfer from other hospitals and previous antibiotic usage are important risk factors for ESBL production. However ESBL production may not be associated with a poorer outcome if appropriate early antibiotic therapy is instituted.     

Extended-spectrum beta-lactamases: implications for the clinical microbiology laboratory, therapy, and infection control

Extended-spectrum beta-lactamase (ESBL) producing gram-negative bacilli are a growing concern in human medicine today. When producing these enzymes, organisms (mostly K. pneumoniae and E. coli) become highly efficient at inactivating the newer third-generation cephaloporins (such as cefotaxime, ceftazidime, and ceftriaxone). In addition, ESBL-producing bacteria are frequently resistant to many classes of non-beta-lactam antibiotics, resulting in difficult-to-treat infections. This review gives an introduction into the topic and is focused on various aspects of ESBLs; it covers the current epidemiology, the problems of ESBL detection and the clinical relevance of infections caused by ESBL-producing organisms. Therapeutic options and potential strategies for dealing with this growing problem are also discussed in this article.     

Risk factors for cervicitis among women with bacterial vaginosis

BACKGROUND: Cervicitis commonly occurs in women with bacterial vaginosis (BV), often without concomitant chlamydial or gonococcal infection. The risk factors for cervicitis have not been described. METHODS: We characterized the risk factors for cervicitis, which is defined as endocervical mucopurulent discharge or easily induced bleeding, among women with BV who were 14-45 years of age. Associations between cervicitis and the characteristics of the subjects, including the presence of specific vaginal bacteria and chlamydial or gonococcal infection detected by strand displacement assay, were analyzed. RESULTS: Of 424 women with BV, 63 (15%) had cervicitis. Of these 63 women, only 8 (13%) had chlamydia or gonorrhea. The risk factors for cervicitis, adjusted for variables, included older age (P<.001, for trend), 相似文献   

Phenotypic and genotypic characterization of fecal Escherichia coli isolates with decreased susceptibility to fluoroquinolones: results from a large hospital-based surveillance initiative

BACKGROUND: The prevalence of fecal colonization with Escherichia coli that has reduced susceptibility to fluoroquinolones is unknown. A detailed characterization of such isolates is limited. METHODS: We conducted 3 annual fecal surveillance initiatives at 2 hospitals from 2002 to 2004. All E. coli isolates with reduced susceptibility to fluoroquinolones (minimum inhibitory concentration [MIC] to levofloxacin, > or = 0.125 microg/mL) were identified. We characterized gyrA and parC mutations and organic solvent tolerance (OST). Isolates were compared using pulsed-field gel electrophoresis. RESULTS: Of 789 fecal samples, 149 (18.9%) revealed E. coli with reduced susceptibility to fluoroquinolones. Of 149 isolates, 102 (68.5%) had a MIC > or = 8 microg/mL, 138 (92.6%) had > or = 1 gyrA mutation, 101 (67.8%) had > or = 1 parC mutation, and 59 (39.6%) demonstrated OST. Isolates with a MIC > or = 8 versus <8 microg/mL had more target mutations (median, 3 vs. 1; P<.001) and more often exhibited OST (51% vs. 15%; P<.001). Of 149 isolates, 144 (96.6%) demonstrated a MIC > or = 16 microg/mL to nalidixic acid. The prevalence of OST differed across study years (P = .01). There was no clonal spread of isolates. CONCLUSIONS: Colonization by E. coli with reduced fluoroquinolone susceptibility is common, and fluoroquinolone-resistance characteristics differ significantly over time. Resistance to nalidixic acid may be useful in the identification of E. coli with early resistance mutations.     

Prognostic factors and antibiotics in Vibrio vulnificus septicemia

BACKGROUND: Immunocompromised patients with Vibrio vulnificus septicemia are at high risk for fatality. When a hemorrhagic bullous necrotic cutaneous lesion (HBNCL) and decreased blood pressure develop, approximately 50% of V vulnificus septicemic patients die within 48 hours. This study aimed to evaluate the risk factor(s) for fatality among patients with V vulnificus septicemia, emphasizing the role of prescribed antimicrobial agents in general and the therapeutic efficacy of the combination of a third-generation cephalosporin and tetracycline or its analogue in particular. METHODS: Patients with the diagnosis of V vulnificus infection admitted to 5 large medical centers in Taiwan between 1995 and 2003 were included in this retrospective study. Patients were divided into 2 groups: those without [corrected] HBNCLs (group 1) [corrected] and those with [corrected] HBNCLs (group 2) [corrected]Patients were further divided into subgoups with [corrected] fatalities (fatal subgroup) and those without fatalities (nonfatal subgroup). RESULTS: A total of 93 patients participated in the study. In group 1, the fatal subgroup had higher Acute Physiology and Chronic Health Evaluation II (APACHE II) scores (P = .006) and a higher proportion of shock at arrival at the medical center (P = .015) than the nonfatal subgroup. In group 2, the effect of a first- or second-generation cephalosporin plus an aminoglycoside was negative (P = .01) and that of combined third-generation cephalosporin and tetracycline or its analogue was positive (P<.001); significant differences were found between the fatal and nonfatal subgroups in the APACHE II score (P<.001), number who were in shock at arrival at the medical center (P = .02), delayed surgical intervention (P = .03), and peripheral leukocytosis (P = .03). Shock at arrival at the medical center (odds ratio [OR], 19.25; 95% confidence interval [CI], 1.768-209.54; P = .02) was an independent risk factor for fatality in patients without HBNCLs. Use of a third-generation cephalosporin and tetracycline or its analogue significantly reduced fatality rates in patients with HBNCLs (OR, 0.037; 95% CI, 0.007-0.192; P<.001). CONCLUSION: Septic shock is a determinant of fatality in patients with V vulnificus septicemia without HBNCLs; our data suggest that the combination of a third-generation cephalosporin and tetracycline or its analogue may be a better choice in antimicrobial treatment of V vulnificus septicemic patients with HBNCLs.