Sheng-Kang Chiu

National surveillance study on carbapenem non-susceptible Klebsiella pneumoniae in Taiwan: the emergence and rapid dissemination of KPC-2 carbapenemase

Objectives The global spread and increasing incidence of carbapenem non-susceptible Klebsiella pneumoniae (CnSKP) has made its treatment difficult, increasing the mortality. To establish nationwide data on CnSKP spread and carbapenem-resistance mechanisms, we conducted a national surveillance study in Taiwanese hospitals. Methods We collected 100 and 247 CnSKP isolates in 2010 and 2012, respectively. The tests performed included antibiotic susceptibility tests; detection of carbapenemase, extended-spectrum β-lactamases (ESBL), and AmpC β-lactamases genes; outer membrane porin profiles; and genetic relationship with pulsed-field gel electrophoresis and multilocus sequence type. Results The resistance rate of CnSKP isolates to cefazolin, cefotaxime, cefoxitin, ceftazidime, and ciprofloxacin was over 90%. Susceptibility rate to tigecycline and colistin in 2010 was 91.0% and 83.0%, respectively; in 2012, it was 91.9% and 87.9%, respectively. In 2010, carbapenemase genes were detected in only 6.0% of isolates (4 bla IMP-8 and 2 bla VIM-1). In 2012, carbapenemase genes were detected in 22.3% of isolates (41 bla KPC-2, 7 bla VIM-1, 6 bla IMP-8, and 1 bla NDM-1). More than 95% of isolates exhibited either OmpK35 or OmpK36 porin loss or both. Impermeability due to porin mutation coupled with AmpC β-lactamases or ESBLs were major carbapenem-resistance mechanisms. Among 41 KPC-2-producing K. pneumoniae isolates, all were ST11 with 1 major pulsotype. Conclusions In 2010 and 2012, the major mechanisms of CnSKP in Taiwan were the concomitance of AmpC with OmpK35/36 loss. KPC-2-KP dissemination with the same ST11 were observed in 2012. The emergence and rapid spread of KPC-2-KP is becoming an endemic problem in Taiwan. The identification of NDM-1 K. pneumoniae case is alarming.

Impact of vancomycin MIC creep on patients with methicillin-resistant Staphylococcus aureus bacteremia

BACKGROUND/PURPOSE To date, vancomycin is still the standard treatment for methicillin-resistant Staphylococcus aureus (MRSA) infections, but minimum inhibitory concentration (MIC) creep is becoming a major concern. The aims of this study were to investigate trends in vancomycin use and MIC values over the last decade at our institute and to evaluate the outcomes of bacteremic patients infected with MRSA isolates with reduced vancomycin susceptibility. METHODS Vancomycin use and density were evaluated using the defined daily doses (DDD) method. Patients with MRSA bacteremia were enrolled retrospectively. Patient demographic data and clinical outcomes were analyzed. The first isolate from each patient was collected for E-testing in order to determine vancomycin MIC. MIC trends were assessed as MIC(50), MIC(90), and the geometric mean. RESULTS Vancomycin use has increased over the last decade. One hundred and forty patients were enrolled and their respective isolates were retrieved, including isolates from 45 patients in 2001, 46 patients in 2005, and 49 patients in 2009. The geometric mean (± standard deviation) of the vancomycin MIC for MRSA isolates obtained in 2009 was 1.39 ± 0.30 μg/mL, which is significantly higher than the mean vancomycin MIC obtained in 2001 (1.19 ± 0.34 μg/mL, p < 0.01) and 2005 (1.99 ± 0.25 μg/mL, p < 0.001). There were no significant differences in terms of the in-hospital mortality rate between patients with MRSA isolates with MICs ≥ 1.5 μg/mL or < 1.5 μg/mL. CONCLUSION We identified a significant upward trend in the use of vancomycin and its MIC over the last decade. This study shows that patients infected with MRSA isolates with high MICs (≥1.5 μg/mL) do not have a significantly higher mortality rate compared with isolates with low MICs (<1.5 μg/mL).

Risk Factors for Healthcare-Associated Extensively Drug-Resistant Acinetobacter baumannii Infections: A Case-Control Study

The emergence of extensively drug-resistant Acinetobacter baumannii (XDRAB) is a serious threat to hospitalized patients. From 2008 to 2010, surveillance detected 25 hospital-acquired infection (HAI) cases caused by XDRAB at a medical center in Taipei. The site of XDRAB infection was bloodstream (n = 8), urinary tract (n = 12), lower respiratory tract (n = 3), surgical site (n = 1), and cardiovascular (n = 1). The isolates were resistant to all currently available antibiotics except for colistin. The XDRAB isolates are genetically diverse, shown by pulsed-field gel electrophoresis, but 23 of 25 harbored class 1 integron with a 2.3-kb gene cassette. Most of these isolates carry OXA-23 (n = 21) and OXA-51-like carbapenemase genes (n = 25). To identify the risk factors, a case-control study was conducted. The 25 cases were compared with 100 controls randomly selected from hospitalized patients without XDRAB-HAIs, matched by the onset date, ward, and age, at a ratio of 1∶4. Prior use of imipenem, meropenem, piperacillin/tazobactam or fourth-generation cephalosporins (adjusted OR: 3.2, 95% CI: 1.03–10.2, P = 0.04) and >30 days bed-ridden (adjusted OR: 6.0, 95% CI: 1.3–27.6, P = 0.02) were found to be the independent risk factors for XDRAB-HAIs. These findings highlight that, even in the absence of clonal dissemination, XDRAB can emerge under the selective pressure of broad-spectrum antibiotics and causes subsequent HAIs in compromised hosts. An appropriate response to the XDRAB threat therefore should include a component of prudent use of broad-spectrum antibiotics active against gram-negative bacteria.

Candida lipolytica candidemia as a rare infectious complication of acute pancreatitis: A case report and literature review

Candida lipolytica candidemia is a rare but an emerging pathogenic yeast infection in humans. It can gain access to the bloodstream through intravascular catheterization, especially through central venous catheters in immunocompromised or critically ill patients during hospitalization. In this report, we present a noncatheter-related C. lipolytica candidemia infection in an 84-year-old man who was admitted due to acute pancreatitis. The possible pathogenesis and management of C. lipolytica candidemia are highlighted. It was an unusual infectious complication of acute pancreatitis. Clinicians should be aware that such an opportunistic pathogen can lead to invasive candidemia infection. In clinical practice, systemic antifungal therapy and the removal of the potentially infected central venous catheter might be recommended for the treatment of C. lipolytica candidemia.

Methicillin-resistant Staphylococcus aureus bacteremia in hemodialysis and nondialysis patients

BACKGROUND/PURPOSE Increased mortality has been reported in patients treated with vancomycin for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia with high minimum inhibitory concentration (MIC) values within the susceptibility range. However, this finding has not been verified in hemodialysis patients, who have much higher invasive MRSA infection rates than nondialysis patients. We aimed at comparing vancomycin MICs between hemodialysis and nondialysis patients, and identifying predictors of high vancomycin MICs and infection-related mortality in hemodialysis patients with MRSA bacteremia. METHODS Patients with MRSA bacteremia from January 2008 through December 2009 were enrolled. Vancomycin MIC was determined for each first isolate using the Etest method. Clinical characteristics and vancomycin MICs were compared between hemodialysis and nondialysis patients. Factors associated with high vancomycin MIC (2 μg/mL) and infection-related mortality in hemodialysis patients were analyzed. RESULTS A total of 162 MRSA bacteremia episodes were identified. Forty-four (27.0%) isolates were obtained from hemodialysis patients and 118 (73.0%) from nondialysis patients. Diabetes (63.3% vs. 39.8%, p = 0.007) and prior vancomycin exposure in 30 days (31.8% vs. 12.7%, p = 0.005) were more prevalent in hemodialysis group than in nondialysis group. A higher prevalence of vancomycin MIC of 2 μg/mL was observed in hemodialysis group in comparison with nondialysis group (11.4% vs. 1.7%, p = 0.016). In following analyses of hemodialysis group, patients with initial presentation of septic shock had a higher risk of vancomycin MIC of 2 μg/mL than nonseptic shock patients (100.0% vs. 38.5% p = 0.014). Infection-related mortality was associated with age, Acute Physiology and Chronic Health Evaluation II (APACHE-II) score >15, presence of septic shock, receipt of mechanical ventilation, and failure to remove source of bacteremia in univariate analysis. CONCLUSION Hemodialysis patients with MRSA bacteremia are more likely to have a high vancomycin MIC (2 μg/mL) compared with nondialysis patients. Infection-related mortality is associated with the patients clinical manifestations, including age, APACHE-II score >15, presence of septic shock, receipt of mechanical ventilation, and failure to remove source of bacteremia. Treatment selection should be tailored according to the patients clinical condition.

Infectious sacroiliitis caused by Staphylococcus aureus following acupuncture: a case report

Determination of the origin of infectious sacroiliitis (ISI), a rare form of septic arthritis, is often time consuming and clinically difficult owing to its various presentations, which include joint, skin and urinary tract infections. This report describes the diagnosis, determination of infectious origin and treatment of a case of ISI attributed to the use of acupuncture for the treatment of lower back pain. We report on a 61-year-old man who developed right hip pain and fever 3 days after undergoing acupuncture over the right buttock region for the treatment of lower back pain. Blood culture showed infection with methicillin-susceptible Staphylococcus aureus and MRI disclosed the presence of an inflamed area over the right iliac bone and the right portion of the sacrum. The patient was cured after a 4-week course of antimicrobial treatment. Clinicians should take a history of acupuncture use when evaluating patients presenting with fever of unknown origin and/or bacteraemia and consider the possibility of ISI when evaluating patients with hip pain and infectious signs after acupuncture or other possible causes of infection. This indicates the importance of performing clinically clean procedures to prevent septic complications when treating patients with acupuncture.

Tigecycline resistance among carbapenem-resistant Klebsiella Pneumoniae: Clinical characteristics and expression levels of efflux pump genes

Objectives Tigecycline is a treatment option for infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP). Emerging tigecycline resistance in CRKP represents a growing threat. Knowledge of the clinical, microbiological, and molecular characteristics of tigecycline- and carbapenem-resistant Klebsiella pneumoniae (TCRKP) is limited. Methods Patients infected with TCRKP were identified from a Taiwanese national surveillance study. Clinical data were collected from medical records. We performed susceptibility tests, carbapenemase gene detection, pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). Furthermore, we performed quantitative real-time polymerase chain reaction (qRT-PCR) analyses to assess the expression levels of the efflux pump genes acrB and oqxB. Results We identified 16 patients infected with TCRKP, with urinary tract infection (UTI) being the most common type of infection (63%). The all-cause 30-day mortality rate was 44% in patients with TCRKP infection. Patients with a site of infection other than the urinary tract had a significantly higher mortality rate than patients with UTIs (83% vs. 20%, p = 0.035). PFGE and MLST revealed no dominant clone or sequence type. Using qRT-PCR, overexpression of both the acrB and oqxB genes was identified in seven isolates, and overexpression of the oqxB gene was observed in another seven. There was poor correlation between acrB or oqxB expression and tigecycline MICs (r = -0.038 and -0.166, respectively). Conclusions The mortality rate in patients infected with TCRKP in this study was 44% and this is an important subset of patients. The absence of a linear relationship between efflux pump genes expression and MICs indicates that tigecycline resistance may be mediated by other factors. Continuous monitoring of tigecycline resistance among CRKP isolates and resistance mechanisms are necessary.

Roles of ramR and tet(A) mutations in conferring tigecycline resistance in carbapenem-resistant Klebsiella pneumoniae clinical isolates

ABSTRACT Tigecycline is regarded as a last-resort treatment for carbapenem-resistant Klebsiella pneumoniae (CRKP) infections, but increasing numbers of tigecycline-resistant K. pneumoniae isolates have been reported. The tigecycline resistance mechanisms in CRKP are undetermined. This study aimed to elucidate the mechanisms underlying tigecycline resistance in 16 tigecycline- and carbapenem-resistant K. pneumoniae (TCRKP) isolates. Mutations in tigecycline resistance determinant genes [ramR, acrR, oqxR, tet(A), tet(L), tet(X), tet(M), rpsJ] were assessed by PCR amplicon sequencing, and mutations in ramR and tet(A) exhibited high prevalences individually (81%) and in combination (63%). Eight functional ramR mutation profiles reducing tigecycline sensitivity were verified by plasmid complementation of wild-type and mutant ramR. Using a site-specific mutant, the most frequent RamR mutation, A19V (60%), had no significant effect on tigecycline susceptibility or the upregulation of ramA and acrA. Two tet(A) variants with double frameshift mutations, type 1 and type 2, were identified; type 2 tet(A) is novel. A parent strain transformed with a plasmid carrying type 1 or type 2 tet(A) increased the tigecycline MIC by 8-fold or 4-fold, respectively. Synergistic effects were observed in strains harboring no ramR gene and a mutated tet(A), with an 8-fold increase in the tigecycline MIC compared with that in strains harboring only mutated tet(A) being seen. Overall, mutations in the ramR and tet(A) efflux genes constituted the major tigecycline resistance mechanisms among the studied TCRKP isolates. The identification of strains exhibiting the combination of a ramR deficiency and widespread mutated tet(A) is concerning due to the possible dissemination of increased tigecycline resistance in K. pneumoniae.

Applying ATP bioluminescence to design and evaluate a successful new intensive care unit cleaning programme

This was a two-phase prospective intervention study in the cardiology intensive care unit (CICU) and medical intensive care unit (MICU) and of a public 1800-bed medical centre in Taiwan. In phase I, cleaning efficacy was monitored by ATP bioluminescence after daily morning cleaning, and only 43.9% of 221 tested surfaces passed. The baseline data were used to define an intervention consisting of a new cleaning protocol as well as a new education/training programme. In phase II, following the intervention, 88.1% of 270 surfaces were found to be clean. The combined infection rate in the CICU and MICU showed a statistically significant decrease of 49.7%.

Chryseobacterium indologenes peritonitis in a patient with malignant ascites

Chryseobacterium indologenes is an uncommon pathogen of human disease and is usually associated with indwelling devices or immunocompromised hosts. We report here an unusual case of C. indologenes peritonitis in an oncological patient with malignant ascites. The patient was treated successfully by trimethoprim–sulfamethoxazole without removal of the catheter.