Tom Chiang

Enteroaggregative Escherichia coli Is a Cause of Acute Diarrheal Illness: A Meta-Analysis

BACKGROUND Conflicting studies exist regarding the role of enteroaggregative Escherichia coli (EAEC) as a cause of acute diarrheal illness. The objective of this meta-analysis was to determine whether identification of EAEC in stool samples is associated with acute diarrheal illness among different subpopulations, by geographic area. METHODS A comprehensive search of electronic bibliographic databases (Medline and PubMed) from August 1985 to January 2006, as well as a search of conference proceedings, references of articles, and contacts with investigators of EAEC, yielded 354 studies. RESULTS Forty-one studies (12%) that met the selection criteria (i.e., that examined the association between acute diarrheal illness and the excretion of EAEC among different subpopulations) were included. In this meta-analysis, presence of EAEC identified with the HEp-2 cell adherence assay was found to be significantly associated with acute diarrheal illness among children residing in developing regions (odds ratio [OR], 1.58; 95% confidence interval [CI], 1.36-1.83) and industrialized regions (OR, 1.23; 95% CI, 1.03-1.48), adults with human immunodeficiency virus infection residing in developing regions (OR, 6.43; 95% CI, 2.91-14.16), adults residing in developing regions (OR, 7.15; 95% CI, 1.96-26.04), and international travelers to developing regions (OR, 6.72; 95% CI, 2.62-17.20). A limited number of studies were available that examined the role of EAEC identified by its virulence genes by a DNA probe. CONCLUSIONS On the basis of this meta-analysis, we conclude that EAEC is a cause of acute diarrheal illness among many different subpopulations in both developing and industrialized regions, that EAEC strains are very heterogeneous and that additional studies that examine the role of EAEC in acute diarrheal illness are needed.

The prevalence and virulence characteristics of enteroaggregative Escherichia coli at an urgent-care clinic in the USA : a case-control study

This case-control study examined the prevalence of enteroaggregative Escherichia coli (EAEC), its genes and elicited inflammatory response, and the stool characteristics of adult patients with and without acute diarrhoeal illness presenting to an urgent-care clinic in the USA. A total of 1004 individual stool specimens (253 from patients with acute diarrhoeal illness and 751 from patients without diarrhoeal illness) were collected between 1 June 2003 and 30 June 2008. EAEC was identified as the sole cause of acute diarrhoeal illness in 6 % (n=15) of patients and in 2 % (n=15) without diarrhoeal illness. Control patients (n=15) were similar to case patients (n=15) for age, gender and co-morbidities. The EAEC genes aggR, aap, aat, astA and/or set1A were identified more frequently in case patients compared with control patients (P <0.05). aggR-positive EAEC elicited higher levels of interleukin (IL)-1ra, IL-6, IL-8 and tumour necrosis factor-alpha compared with aggR-negative EAEC during co-incubation with HCT-8 cells. Patients with EAEC diarrhoea and isolates with the genes aggR, aap, aatA, astA or set1A had stools characterized by gross mucus and the presence of faecal leukocytes (P <0.05). These results indicate that EAEC is a potential cause of acute diarrhoeal illness affecting patients presenting to an acute-care clinic in the USA and suggest that aggR, aap, aatA, astA and set1A may be markers for virulence.

Identification of Carbapenem-Resistant Klebsiella pneumoniae Harboring KPC Enzymes in New Jersey

Klebsiella pneumoniae isolates harboring KPC enzymes have been identified in many geographical areas since 2001. Numerous problems exist in the detection and treatment of patients with such isolates. The clinical characteristics and molecular epidemiology associated with 12 randomly chosen patients in whom these enzymes were detected by molecular methods are described. This is the first description of the identification of carbapenem-resistant K. pneumoniae isolates harboring KPC beta-lactamases at the Veterans Administration Hospital in New Jersey (VA NJHCS). Because recognition of carbapenem resistance in K. pneumoniae due to KPC enzymes can only be achieved by molecular methods, detection in the Clinical Microbiology Laboratory by routine methods will continue to be difficult, leading to dilemmas in treatment.

Virulence and Plasmid Transferability of KPC Klebsiella pneumoniae at the Veterans Affairs Healthcare System of New Jersey

Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae infections are associated with high mortality; however, little is known about the virulence determinants of KPC-producing K. pneumoniae. At the Veterans Affairs New Jersey Healthcare System (VA NJHCS), we investigated the virulence and plasmid transferability of 60 clinically unique KPC-containing K. pneumoniae isolates. All 60 isolates were negative for known virulence factors K1, K2, and K5 capsular antigens; rmpA; and the aerobactin gene by polymerase chain reaction. Isolates varied in their susceptibility to neutrophil phagocytosis, but were less resistant than the virulent serotype K1 isolate. Additionally, no deaths were seen on murine lethality studies. Conjugation results of this study showed that the bla(KPC) gene can be transferred into an Escherichia coli J-53 strain but not to E. coli JP-995. However, the stability is very limited as E. coli J-53 does not retain bla(KPC)-containing plasmids for any period of time. The lack of virulence factors in the set of KPC-producing K. pneumoniae studied suggests that morbidity and mortality may be due to detection issues or lack of effective antibiotics.

Impact of adding maraviroc to antiretroviral regimens in patients with full viral suppression but impaired CD4 recovery

We reviewed the effect of adding maraviroc on CD4 cell counts in nine patients on antiretroviral therapy with full viral suppression but impaired CD4 cell recovery. There were no significant differences in changes in CD4 cell count, percentage of CD4 cells, or in the ratio of CD4/CD8 cells at 30 days and 25 weeks of maraviroc therapy. Plasma endotoxin levels measured in four patients before and during maraviroc treatment also showed no significant differences.

Plasmid transferability of KPC into a virulent K2 serotype Klebsiella pneumoniae

BackgroundKPC-producing carbapenem-resistant Klebsiella pneumoniae (CRKP) infections are associated with high mortality; however, their virulence determinants are not well defined.MethodsWe investigated the virulence and plasmid transferability among KPC-containing K. pneumoniae isolates.ResultsKPC-2 and -3 were successfully conjugated and retained by a virulent K2 K. pneumoniae recipient isolate. Antimicrobial susceptibility testing showed KPC-2 and -3 donor strains were resistant to more than four classes of antibiotics while the K2 isolate was only initially resistant to ampicillin. After conjugation of KPC-2 and -3, the K2 K. pneumoniae transconjugants became resistant to all beta-lactams. Additionally, the KPC K2 K. pneumoniae transconjugants continued to retain its high serum resistance and murine lethality.ConclusionsConjugation and retainment of KPC by virulent K2 K. pneumoniae and the ability of the tranconjugants to maintain its high serum resistance and murine lethality after conjugation was demonstrated in this study. These findings are concerning for the potential of KPC-like genes to disseminate among virulent K. pneumoniae isolates.

Increased mortality associated with a clonal outbreak of ceftazidime-resistant Klebsiella pneumoniae: a case-control study.

OBJECTIVES To determine risk factors for ceftazidime-resistant Klebsiella pneumoniae infection and the effect of ceftazidime-resistant K. pneumoniae infection on mortality during an isolated outbreak. DESIGN Case-control investigation using clinical and molecular epidemiology and prospective analysis of infection control interventions. SETTING Surgical intensive care unit of a university-affiliated community hospital. PATIENTS Fourteen case-patients infected with ceftazidime-resistant K. pneumoniae and 14 control-patients. RESULTS Ten of 14 case-patients had identical strains by pulsed-field gel electrophoresis. Broad-spectrum antibiotic therapy before admission to the unit was strongly predictive of subsequent ceftazidime-resistant K. pneumoniae infection. In addition, patients with ceftazidime-resistant K. pneumoniae infection experienced increased mortality (odds ratio, 3.77). CONCLUSIONS Cephalosporin restriction has been shown to decrease the incidence of nosocomial ceftazidime-resistant K. pneumoniae. However, isolated clonal outbreaks may occur due to lapses in infection control practices. Reinstatement of strict handwashing, thorough environmental cleaning, and repeat education led to termination of the outbreak. A distinct correlation between ceftazidime-resistant K. pneumoniae infection and mortality supports the important influence of antibiotic resistance on the outcome of serious bacterial infections.

K2 Serotype Klebsiella pneumoniae Causing a Liver Abscess Associated with Infective Endocarditis

ABSTRACT Klebsiella pneumoniae primary liver abscess (KPLA) is an emerging disease that is associated with distant septic complications. We report the first case of KPLA associated with infective endocarditis. The K. pneumoniae strain was a hypermucoid K2 serotype carrying the rmpA virulence-associated gene.

Refractory Clostridium difficile Infection Successfully Treated with Tigecycline, Rifaximin, and Vancomycin.

The occurrence of Clostridium difficile colitis is on the rise and has become more difficult to manage with standard therapy. Thus, the need for alternative treatments is essential. Tigecycline is a glycylcycline antibiotic that has been shown to be effective against C. difficile through several published case reports and in in vitro studies. We present a case of C. difficile colitis that failed to respond to metronidazole and oral vancomycin therapy, but improved on a combination of rifaximin, tigecycline, and vancomycin.

Challenges to Conducting a Clinical Trial of Combination Therapy of Colistin and Rifampicin for Extensively Drug-Resistant Acinetobacter baumannii

TO THE EDITOR—We commend DuranteMangoni and colleagues [1] for conducting a study of examining the potential role of combination therapy of colistin and rifampicin for the treatment of serious infections due to extensively drugresistant (XDR) Acinetobacter baumannii. Identifying treatments for XDR A. baumannii is an obvious high unmet medical need because of the increased mortality rates identified in critically ill patients and the dearth of antibiotics available to treat these patients. Durante-Mangoni and colleagues [1] randomized 210 patients with lifethreatening infections due to XDR A. baumannii at a 1:1 ratio to either colistin alone (2 MU every 8 hours) or colistin plus rifampicin (600 mg every 12 hours), both given intravenously. The treatment duration was left up to the investigator. The primary end point was overall 30-day mortality. Results indicated that the 30-day mortality was 43%, without difference between treatment arms (P = .95). The authors conclude that “[i]n serious XDR A. baumannii infections, 30-day mortality is not reduced by addition of rifampicin to colistin.” We believe that 3 confounding variables were not addressed a priori before the initiation of this head-to-head comparison of colistin versus colistin plus rifampicin. Because of these confounding variables, it is difficult to determine whether or not there is a true lack of difference between these 2 treatments. First, the patient population enrolled and randomized was a very heterogeneous population. The population was inherently complex, as evidenced by the percentage of patients with a Charlson comorbidity index of ≥3 (33% of all patients) and the severity of the underlying illness (mean Simplifed Acute Physiology Score II, 39.9). It is unknown whether the combination therapy would be effective in a specific primary diagnosis or a homogenous population. Second, the patients were not stratified by the additional antibiotics that are known to be effective for A. baumannii (eg, tigecycline and carbapenems [meropenem]). Although patients were infected with XDR A. baumannii (ie, resistance to tigecycline and carbapenems), in combination with colistin, these additional antibiotics may result in a synergistic effect [2]. The authors acknowledge that “Meropenem was employed in the control arm more frequently than in the experimental arm (15.9% vs 3.9%), whereas the reverse occurred with tigecycline (4.9% in the control arm vs 10.9% in the experimental arm).” Although these differences were not statistically significant, post hoc analyses to evaluate the contribution of these antibiotics on 30-day mortality are necessary to see what impact, if any, they have on the primary end point of 30-day mortality. Furthermore, mortality differences are known to be increased with the use of tigecycline compared with comparator antibiotics, especially for the indication of ventilator-associated pneumonia, bloodstream infections, or hospital acquired-pneumonia. In patients with ventilator-associated pneumonia and baseline bacteremia, mortality was 50.0% (9 of 18 patients) for tigecycline [3]. Patients with these primary diagnoses made up 98.5% of all patients in the trial. Third, therapeutic drug monitoring for colistin was not available. It is widely known that rifampicin causes drug-drug interactions. It causes drug-drug interactions with other concomitantly administered medications for diagnoses that were most likely the reasons for hospital admission in the first place. Consequently, drug-drug interactions with these medications may have affected the primary end point in this study—30-day mortality. Importantly, rifampicin mediates cytochrome P450 enzyme induction and the P-glycoprotein transport system, which may have altered drug clearance and consequently therapeutic treatment outcome of colistin or additional antimicrobial agents used in this study [4]. Despite these confounding variables in this study, XDR A. baumannii eradication from the primary source of infection was more frequently observed with the combination of colistin and rifampicin than with colistin alone, consistent with previous in vitro findings. There are other examples of antibiotics that show statistically significant differences in microbiological outcomes but not in clinical outcomes [5]. These examples reinforce findings indicating that microbiological outcomes do not always translate into clinical outcomes and that studies in a heterogeneous patient population may be difficult to interpret. It is also important to note that just because the authors concluded that 30day mortality did not differ between