Jia-Bin Li

Emergence of CTX-M-3, TEM-1 and a new plasmid-mediated MOX-4 AmpC in a multiresistant Aeromonas caviae isolate from a patient with pneumonia.

Aeromonas species rarely cause pulmonary infection. We report, for what is believed to be the first time, a case of severe pneumonia in a cancer patient caused by Aeromonas caviae. Detailed microbiological investigation revealed that this isolate carried three beta-lactamase-encoding genes (encoding MOX-4, CTX-M-3 and TEM-1) conferring resistance to all beta-lactams but imipenem. The beta-lactamase with a pI of 9.0 was transferred by conjugation and associated with a 7.3 kb plasmid, as demonstrated by Southern blot hybridization. Analysis of the nucleotide and amino acid sequences showed a new ampC gene that was closely related to those encoding the MOX-1, MOX-2 and MOX-3 beta-lactamases. This new plasmid-mediated AmpC beta-lactamase from China was named MOX-4. This is believed to be the first report of MOX-4, CTX-M-3 and TEM-1 beta-lactamases in a multiresistant A. caviae.

Characterization of two plasmid-encoded cefotaximases found in clinical Escherichia coli isolates: CTX-M-65 and a novel enzyme, CTX-M-87.

Three clinical strains of Escherichia coli (p168, p517 and p667) were collected in 2006 from three hospitals in Anhui Province (China). PCR and DNA sequencing revealed that E. coli p168 carried a novel extended-spectrum beta-lactamase (ESBL), which was designated CTX-M-87. The extended-spectrum beta-lactamase which was carried by E. coli p517 and E. coli p667 was previously named CTX-M-65. The deduced amino acid sequence of CTX-M-87, with pI 9.1, differed from that of CTX-M-14 by the substitutions Ala77-->Val and Pro167-->Leu. Like CTX-M-14, CTX-M-87 had a more potent hydrolytic activity against cefotaxime than against ceftazidime and had high affinity for cefuroxime and cefotaxime. These data show that mutations at position 167 in CTX-M do not always affect catalytic activity and substrate preference.

In vivo activity of daptomycin/colistin combination therapy in a Galleria mellonella model of Acinetobacter baumannii infection

Antimicrobial treatment of multidrug-resistant Acinetobacter baumannii (MDR-AB) infections continues to pose significant challenges. With limited options, clinicians have been pushed towards using unorthodox combinations of licensed antibiotics. Although daptomycin/colistin combination appears to be a promising treatment option based on in vitro data, further preclinical work is needed. In this study, the A. baumannii-Galleria mellonella system was employed to study the in vivo efficacy of this combination in order to determine whether it should be explored further for the treatment of MDR-AB infections. The antimicrobial activity of colistin alone and in combination with daptomycin was assessed versus an A. baumannii type strain (ATCC 19606) and a MDR-AB clinical strain (GN2231) isolated in Anhui, China. Synergy studies were performed using the microtitre plate chequerboard assay and time-kill methodology. The in vivo activity of daptomycin/colistin combination was assessed using a G. mellonella larvae model. The combination of daptomycin and colistin was bactericidal against both strains tested. In chequerboard assays, daptomycin was highly active against A. baumannii when combined with colistin [fractional inhibitory concentration index (FICI) of <0.5]. Treatment of G. mellonella larvae infected with lethal doses of A. baumannii resulted in significantly enhanced survival rates when daptomycin was given with colistin compared with colistin treatment alone (P<0.05). This work suggests that daptomycin/colistin combination is highly active against A. baumannii both in vitro and in a simple invertebrate model of infection.

Reactivation of hepatitis B virus after steroid treatment in rheumatic diseases.

To the Editor: Hepatitis B virus (HBV) infection is a global problem and is particularly endemic in some regions of the world. More than one-third of the world’s population has been infected with the HBV and there are 350 million people with chronic infection; 75% of them live in Southeast Asia and the Western Pacific regions1,2. There is a chance of reactivation of a previous HBV infection in patients undergoing chemotherapy or immunosuppressive therapy for rheumatism, malignancies, autoimmune hepatitis, and systemic lupus erythematosus (SLE); this reactivation is a major cause of morbidity and mortality3. Reactivation of HBV was first described by Wands, et al , who in 1975 reported the condition in 20 patients with lymphoproliferative and myeloproliferative disorders4,5. Induced immunosuppression allows a rapid increase in viral replications and antigen expression. Restoration of immune function causes rapid, T cell–mediated destruction of HBV-infected hepatocytes that manifests clinically as asymptomatic self-limiting anicteric hepatitis to severe hepatitis, potentially fatal progressive decompensated hepatitis, and even death6. In routine clinical practice, it is common to come across patients with rheumatic diseases who have HBsAg-positive serology (“overt” carriers). It is estimated that 21%–67% are affected (mean 50%), with a mean mortality rate of 20%6,7,8. However, clinical events can also develop in “occult” carriers, i.e., patients who are HBsAg-negative but positive for other markers of prior exposure to the virus, including HBcAb alone or in combination with HBsAb. Further, about 12% of anti-core-positive subjects (HBsAg-negative) experience reemergence of HBsAg (seroreversion)6,9. Several risk factors have … Address correspondence to Dr. J-B. Li; E-mail: lijiabin948{at}vip.sohu.com

Surveillance of antimicrobial susceptibility patterns among Shigella species isolated in China during the 7-year period of 2005-2011.

Background Shigella is a frequent cause of bacterial dysentery in the developing world. Treatment with antibiotics is recommended for shigellosis, but the options are limited due to globally emerging resistance. This study was conducted to determine the frequency and pattern of antimicrobial susceptibility of Shigella in China. Methods We studied the antimicrobial resistance profiles of 308 Shigella spp. strains (260 S. flexneri, 40 S. sonnei, 5 S. boydii, and 3 S. dysenteriae) isolated from fecal samples of patients (age, from 3 months to 92 yr) presenting with diarrhea in different districts of Anhui, China. The antimicrobial resistance of strains was determined by the agar dilution method according to the CSLI guidelines. Results The most common serogroup in the Shigella isolates was S. flexneri (n=260, 84.4%), followed by S. sonnei (n=40, 13.0%). The highest resistance rate was found for nalidixic acid (96.4%), followed by ampicillin (93.2%), tetracycline (90.9%), and trimethoprim/sulfamethoxazole (80.8%). Among the isolates tested, 280 (91.0%) were multidrug resistant (resistant to ≥2 agents). The most common resistance pattern was the combination of ampicillin, tetracycline, and trimethoprim/sulfamethoxazole (70.8%). Resistance to ampicillin and tetracycline were more common among S. flexneri than among S. sonnei isolates. Conclusions S. flexneri is predominant in Anhui, China, and its higher antimicrobial resistance rate compared with that of S. sonnei is a cause for concern. Continuous monitoring of resistance patterns is necessary to control the spread of resistance in Shigella. The recommendations for antimicrobial treatment must be updated regularly based on surveillance results.

New Delhi Metallo-β-Lactamase-Mediated Carbapenem Resistance: Origin, Diagnosis, Treatment and Public Health Concern

Objective: To review the origin, diagnosis, treatment and public health concern of New Delhi metallo-&bgr;-lactamase (NDM)-producing bacteria. Data Sources: We searched database for studies published in English. The database of PubMed from 2007 to 2015 was used to conduct a search using the keyword term “NDM and Acinetobacter or Enterobacteriaceae or Pseudomonas aeruginosa.” Study Selection: We collected data including the relevant articles on international transmission, testing methods and treatment strategies of NDM-positive bacteria. Worldwide NDM cases were reviewed based on 22 case reports. Results: The first documented case of infection caused by bacteria producing NDM-1 occurred in India, in 2008. Since then, 13 blaNDM variants have been reported. The rise of NDM is not only due to its high rate of genetic transfer among unrelated bacterial species, but also to human factors such as travel, sanitation and food production and preparation. With limited treatment options, scientists try to improve available therapies and create new ones. Conclusions: In order to slow down the spread of these NDM-positive bacteria, a series of measures must be implemented. The creation and transmission of blaNDM are potentially global health issues, which are not issues for one country or one medical community, but for global priorities in general and for individual wound care practitioners specifically.

Increase in the Prevalence of Resistance Determinants to Trimethoprim/Sulfamethoxazole in Clinical Stenotrophomonas maltophilia Isolates in China

Aims This study was carried to reveal the genetic mechanisms of trimethoprim/sulfamethoxazole (SXT) resistance. Methods Among 300 clinical Stenotrophomonas maltophilia isolates from China, resistance determinants such as sul and dfrA genes, integrons and transposase were examined using PCR, DNA sequencing and thermal asymmetric interlaced PCR (TAIL-PCR). Data were analyzed using SPSS 20.0. Results Of the 300 isolates, 116 (38.7%) were resistant to SXT. An alarming trend of increased resistance to SXT were found over the 10-year period. The positive rates of sul and class 1 integrase (intI1) increased gradually with the development of SXT resistance over the 10-year period. Multiple logistic regression analyses indicated that the genes of qacEΔ1-sul1 (81% vs 46.2%, p = 0.000), sul2 (50.9% vs 9.8%, p = 0.000), intI1 (83.6% vs 65.8%, p = 0.000), dfrA12 (25% vs 3.3%, p = 0.000), dfrA17 (15.5% vs 3.8%, p = 0.000) and dfrA27 (4.3% vs 1.6%, p = 0.01) were more prevalent in SXT-resistant isolates than SXT-susceptible isolates except dfrA1(p = 0.83) and dfrA5(p = 0.18). Sequencing data revealed 12 types of resistance gene cassettes (aar-3-dfrA27, dfrA12–aadA2, dfrA17–aadA5, cmlA1, aacA4, aadA5, arr-3-aacA4, aadA1, aadB–aadA4, aacA4–catB8–aadA1, aadB–aac(6′)-II–blaCARB-8 and aac(6′)-II–blaCARB-8) located in the class 1 integron in 163 isolates (87% SXT-resistant vs 33.7% SXT-susceptible isolates, p = 0.000). A novel finding was the aar-3-dfrA27 (KC748137) gene cassette. The gene of sul2 linked to transposase in 50 SXT- resistant and 7 SXT- susceptible isolates was detected by TAIL-PCR. Conclusions The findings demonstrated a higher prevalence of sul, dfrA, intI1 and resistance gene cassettes in class 1 integron in SXT-resistant clinical S. maltophilia isolates in China. The sul1 and dfrA genes located in integrons and the sul2 linked to transposase may imply wide and rapid dissemination of resistance gene in bacteria.

In vitro synergy of colistin combinations against extensively drug-resistant Acinetobacter baumannii producing OXA-23 carbapenemase.

Fifty extensively drug-resistant Acinetobacter baumannii (XDRAB) were isolated from patients. The chequerboard microdilution method was used to determine the in vitro activities of five colistin (COL)-based combinations including COL+fosfomycin (FOS), COL+rifampicin (RIF), COL+imipenem (IMP), COL+sulbactam (SUP) and COL+levofloxacin (LVX). The synergistic activity was evaluated by the fractional inhibitory concentration index (FICI). According to our results, the combination of COL was synergistic with FOS, RIF, IMP, SUP and LVX with the ratios of 50, 72, 88, 92 and 64%, respectively. When combined with COL, the other five agents showed increased antimicrobial activities. In addition, two of the combinations, COL+RIF and COL+IMP, were more active than the combinations of COL+FOS, COL+SUP and COL+LVX. More importantly, these combination regimens could exert synergistic effects at the sub-minimum inhibitory concentration (MIC) levels against XDRAB strains.

Reduced susceptibility of Candida albicans clinical isolates to azoles and detection of mutations in the ERG11 gene

We investigated the susceptibility of Candida albicans isolated from clinic specimens to azole antifungal agents and estimated the association of the ERG11 mutations with azole resistance during recent 5years in China. In this study, novel mutations G346A, A434V, and L480F in ERG11 may be related to azole resistance in C. albicans.

Detection of plasmid-mediated quinolone resistance determinants and the emergence of multidrug resistance in clinical isolates of Shigella in SiXian area, China

A total of 123 Shigella isolates were collected from SiXian area in Anhui, China. Screening was carried out by polymerase chain reaction (PCR) amplification of plasmid-mediated quinolone resistance (PMQR) determinants. Different β-blactamases genes, plasmid-borne bla(AmpC), 16S rRNA methylase genes, integrons, and mutations in quinolone resistance-determining regions were analysed by PCR for the PMQR-positive isolates.