Chi Jung Wu

Necrotizing fasciitis in patients with liver cirrhosis: predominance of monomicrobial Gram-negative bacillary infections

Necrotizing fasciitis (NF), a rare but severe infection, usually occurs in individuals with underlying chronic illness, but its clinical presentation among cirrhotic patients is infrequently discussed. Forty-two cirrhotic patients with 47 episodes of NF between 1995 and 2006 were analyzed. Their mean age was 55.6 years, with male preponderance (34 patients, 81%). Lower extremities were mainly involved (70%). Of 42 episodes with identified pathogens, 41 (97%) were monomicrobial infections and were caused mainly by Gram-negative rods (GNBs) (32, 76%), including Vibrio (15, 36%), Klebsiella (9, 21%), and Aeromonas spp. (6, 14%). As compared with NF caused by Gram-positive cocci (GPCs), NF caused by GNBs tended to have concurrent bacteremia (81% versus 50%, P=0.09) and initially presented with septic shock (75% versus 30%, P=0.02). However, the in-hospital mortality rate was similar for NF caused by GNBs and GPCs (34% versus 30%, P=1.00). In multivariate analyses, higher sepsis-related organ failure assessment scores (>8) and Child-Pugh class C at initial presentation were independently associated with poor prognoses.

Refractory candidal meningitis in an immunocompromised patient cured by caspofungin

ABSTRACT Candidal meningitis is a rare infectious disease that usually leads to substantial morbidity and mortality. We present a case of candidal meningitis refractory to systemic antifungal therapy (amphotericin B and fluconazole). A 63-year-old female with lymphoblastic lymphoma and myelodysplasia with leukemia transformation developed prolonged fever and headache on the seventh day following intrathecal prophylactic chemotherapy. A lumbar puncture showed neutrophilic pleocytosis, and a cerebrospinal fluid culture yielded Candida albicans. The clinical course was complicated by brain edema, subarachnoid hemorrhage, and hydrocephalus. Parenteral therapy with amphotericin B alone or amphotericin B in combination with fluconazole or intrathecal administration of amphotericin B failed to eradicate C. albicans in the cerebrospinal fluid. After 7 days of caspofungin therapy, however, the cerebrospinal fluid became sterile and the patient gradually regained consciousness. She was discharged 1 month after completing 4 weeks of caspofungin therapy. There were two critical issues we thought to be relevant to the favorable outcome of this case. First, isolation of C. albicans was achieved by inoculating enriched liquid medium with cerebrospinal fluid. Second, there is a potential therapeutic benefit of caspofungin in treating a fungal infection of the central nervous system.

Clostridium difficile Infection at a Medical Center in Southern Taiwan: Incidence, Clinical Features and Prognosis

BACKGROUND/PURPOSE An increase in incidence of Clostridium difficile infection (CDI) among Western countries has been noted in recent years. Epidemiological data of CDI are scarce in Taiwan. This study is intended to depict the clinical features of CDI at a medical center in Southern Taiwan. METHODS From January 1, 2007 to March 31, 2008, hospitalized patients with CDI (defined as the presence of gastrointestinal symptoms and fecal C. difficile toxin) were identified. Their medical records were reviewed for further evaluation. RESULTS A total of 86 cases of CDI were identified in the study period. The incidence was 42.6 cases per 100,000 patient-days, or 3.4 cases per 1,000 discharges, and was highest in intensive care units (110.6 cases per 100,000 patient-days). Variable incidence rates were noted in different wards, and prevalence was higher in the infectious ward. Diarrhea, fever, and abdominal distension were common in 82 (95.3%), 47 (54.7%), and 29 (33.7%) patients, respectively. Metronidazole was the initial therapeutic regimen for 83 (96.5%) patients. Prolonged diarrhea was noted in 31 (36.4%) patients, especially in those on hemodialysis therapy. Recurrence was noted in 7 (8.1%) patients. Fecal carriage of vancomycin-resistant Enterococcus colonization was found in three patients after therapy for CDI. All-cause mortality rate of patients with CDI at 30 days was 23.3%. CONCLUSION CDI is increasingly being recognized within the medical departments, and should be considered in hospitalized adults with diarrhea, fever, or abdominal distension alone, or in combination.

Clinical manifestations, antimicrobial therapy, and prognostic factors of monomicrobial Acinetobacter baumannii complex bacteremia

OBJECTIVES Bacteremia due to Acinetobacter baumannii complex (ABC), which composed of four genomic species (gen. sp.), is a serious and potentially fatal condition. The epidemiology and outcome of such infections due to individual gen. sp. remain undefined. METHODS A retrospective study of patients with monomicrobial ABC bacteremia over six years was conducted at a medical center to determine the association of gen. sp. with clinical outcome. RESULTS Included were 291 patients with monomicrobial ABC bacteremia. Of them, 222 (76.3%) patients had bacteremia caused by gen. sp. 2, i.e. A. baumannii. The presence of multidrug-resistant phenotype was the only independent predictor of Acinetobacter gen. sp. 2 bacteremia (adjusted odd ratio, 7.5; 95% confidence interval, 3.8-14.7; P < 0.001). Patients with Acinetobacter gen. sp. 2 bacteremia had a higher sepsis-related (P = 0.006) and 30 day (P = 0.028) mortality rates than the non-Acinetobacter gen. sp. 2 group. The fatal outcome was independently associated with high SPAS II scores (P = 0.002), rapidly fatal underlying diseases (P = 0.002), bacteremia caused by Acinetobacter gen. sp. 2 (P = 0.01), inappropriate definitive antimicrobial therapy (P < 0.001), and severe sepsis (P < 0.001). CONCLUSION Acinetobacter gen. sp. 2 bacteremia heralded a worse clinical outcome, and therefore the gen. sp. identification of ABC bacteremic isolates is justified.

Complexity of β-lactamases among clinical Aeromonas isolates and its clinical implications.

Aeromonas species, aquatic Gram-negative bacilli, distributed globally and ubiquitously in the natural environment, may be implicated in a variety of human diseases. They can produce various β-lactamases which confer resistance to a broad spectrum of β-lactams, and therefore in vitro susceptibility testing must be used to guide antimicrobial therapy. However, conventional in vitro susceptibility tests may sometimes fail to detect these β-lactamases, and hence raise a therapeutic challenge. In this review article, two chromosomally mediated β-lactamases (i.e., AmpC β-lactamases and metallo-β-lactamases) and acquired extended-spectrum β-lactamases in aeromonads are reviewed, and the clinical implications of the complexity of β-lactamases are discussed.

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 blaTEM, blaPER, blaCTX-M, and blaSHV 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 blaPER-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.

Genome Sequence of a Novel Human Pathogen, Aeromonas aquariorum

Aeromonas aquariorum, a recently described species, is associated with a variety of human diseases. We present here the first genome sequence of A. aquariorum strain AAk1, which was isolated as the sole pathogen from the blood of a patient with septicemia and necrotizing fasciitis.

Distribution and phenotypic and genotypic detection of a metallo-β-lactamase, CphA, among bacteraemic Aeromonas isolates.

The objectives of the study were to investigate the distribution of cphA-related genes (cphA) encoding a CphA metallo-β-lactamase (MBL) among 51 consecutive Aeromonas blood isolates and to compare different phenotypic methods for detecting CphA. The presence of cphA was detected by PCR. Four phenotypic methods, the imipenem-EDTA combined disc test, imipenem-EDTA MBL Etest, agar dilution test and modified Hodge test (MHT), were used to detect imipenem susceptibility and MBL production. The results showed that 35 (69%) blood isolates had cphA. All (100%) of 16 Aeromonas aquariorum isolates and 12 Aeromonas veronii isolates, and 4 (80%) of 5 Aeromonas hydrophila isolates, carried cphA, but none of 15 Aeromonas caviae isolates did. With the standard inocula, irrespective of the presence or absence of cphA, all but one (50, 98%) isolates were susceptible to imipenem tested by disc diffusion, Etest and agar dilution (10(4) c.f.u. spot inocula), and did not exhibit MBL production by the imipenem-EDTA combined disc test and MBL Etest. By the agar dilution test using large inocula (10(7) c.f.u.), 34 (97%) of 35 cphA(+) isolates had imipenem MICs of ≥16 µg ml(-1), higher than the susceptible breakpoint (4 µg ml(-1)), and demonstrated positive results for the MHT, while one cphA(+) and all 17 cphA(-) isolates had imipenem MICs of ≤4 µg ml(-1). In conclusion, the distribution of cphA among aeromonads is species-specific, found in A. aquariorum, A. veronii and A. hydrophila, and the MHT may be a phenotypic screening test for CphA production.

Characterisation of vancomycin-resistant enterococci from hospitalised patients at a tertiary centre over a seven-year period☆

Vancomycin-resistant enterococci (VRE) were isolated from 41 patients at a medical centre in southern Taiwan from 1999 to 2005. This accounted for 0.55% of 7449 patients with clinical colonisation or infection due to Enterococcus species. Nine (22%) patients had clinical infections caused by VRE. Twenty-five (61%) VRE isolates were Enterococcus faecalis with VanA phenotype and vanA gene cluster, the remaining 16 (39%) isolates were Enterococcus faecium with VanB phenotype and vanB (15 isolates) or vanA (1 isolate) gene cluster. The esp gene cluster was found in 6 (24%) E. faecalis isolates and 14 (87.5%) E. faecium isolates, and hyl in 2 (8%) E. faecalis and 6 (37.5%) E. faecium isolates. Analysis of SmaI-digested DNA by pulsed-field gel electrophoresis revealed that most isolates of E. faecalis were distinct, indicating a limited person-to-person spread or sporadic nature of spread. By contrast, 10 (67%) of 15 VanB phenotype E. faecium isolates were identical, suggesting the presence of an occult and limited clonal spread at the hospital. The presence of the esp or hyl gene was not associated with the virulence or outbreak of VRE. In summary, epidemiological data and molecular typing suggest that there was occult clonal spread of VanB phenotype-vanB genotype E. faecium in the surgical ICU, and the limited person-to-person spread or sporadic nature of E. faecalis. Infection control measures are warranted due to the potential for spread of VRE.

Voriconazole inhibition of tacrolimus metabolism in a kidney transplant recipient with fluconazole-resistant cryptococcal meningitis

Fluconazole resistance among Cryptococcus neoformans is unusual in post-transplantation patients. Voriconazole is a triazole agent with good antifungal activity but also with drug-drug interactions because of potent inhibition of the P450 enzyme system. The interaction with immunosuppressive agents, especially calcineurin inhibitors, is of concern in post-transplantation patients. We report the first case of fluconazole-resistant cryptococcal meningitis in a kidney transplant recipient successfully treated with voriconazole, but complicated with a raised serum concentration of tacrolimus and hyponatremia after co-administration. A 43-year-old man with a history of renal transplantation and on long-term immunosuppressive agents, including mycophenolate and tacrolimus, suffered from recurrent cryptococcal meningitis. He was treated with amphotericin B-liposome for 24 days because of fluconazole resistance. However, cryptococci were still found in the cerebrospinal fluid; oral voriconazole was substituted. Six days after co-administration of voriconazole and tacrolimus, the trough concentration of tacrolimus markedly increased and hyponatremia developed. A culture of the CSF did not yield growth of Cryptococcus. Conditions improved after the cessation of tacrolimus for three days followed by reducing the dosage of voriconazole and tacrolimus. When voriconazole is initially added, the dosage of tacrolimus should be reduced. Close monitoring of tacrolimus concentration and its adverse effects, including nephrotoxicity, hyperglycemia, hyperkalemia, and hyponatremia, are mandatory.