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CHINET 2007 surveillance of antimicrobial resistance in Haemophilus influenzae in China
Abstract
Objective: To investigate the antibiotic resistance in clinical isolates of Haemophilus influenzae (HI) in China during 2007. Methods: Clinical isolates of HI were collected from 9 hospitals in China. Antimicrobial susceptibility was tested by Kirby-Bauer method. Results were analyzed according to CLSI 2007. Beta-lactamases were detected by nitrocefin disk test. Results: A total of 755 clinical isolates of HI were collected. About 59.4%, 30.1% and 16.9% of the 755 strains were resistant to trimethoprim-sulfamethoxazole, ampicillin, and chloramphenicol, respectively. No more than 10% of these strains were resistant to ampicillin-sulbactam, ciprofloxacin, ceftazidime, amoxicillin-clavulanic acid, azithromycin, or cefuroxime. About 37.4% of the strains were resistant to ampicillin. Beta-lactamase was produced in 34.9% of the isolates from children. Beta-lactamase-positive strains were more resistant than the isolates from adults (13.7% and 10.6%). Only 1.6% of the isolates from children were resistant to ciprofloxacin, apparently lower than the isolates from adults (19.1%). The overall prevalence of β-lactamase was 27.4%. The prevalence of multidrug-resistant strains was 25.3% (159/609). Conclusions: The resistance of HI to ampicillin and trimethoprim-sulfamethoxazole is increasing. Trimethoprim-sulfamethoxazole should not be used as empirical treatment of HI infection. The resistance rate to ampicillin and prevalence of β-lactamase are higher in children's isolates than in the isolates from adults(P<0.05). The primary mechanism of antibiotic resistance in HI is production of beta-lactamases. More attention should be paid to the multidrug-resistant HI isolated from children.
A very simple and effective approach to nonlinear oscillators is suggested. Anyone with basic knowledge of advanced calculus can apply the method to finding approximately the amplitude-frequency relationship of a nonlinear oscillator. Some examples are given to illustrate its extremely simple solution procedure and an acceptable accuracy of the obtained solutions.
A Hamiltonian approach to nonlinear oscillators is suggested. A conservative oscillator always admits a Hamiltonian invariant, H, which keeps unchanged during oscillation. This property is used to obtain approximate frequency–amplitude relationship of a nonlinear oscillator with acceptable accuracy. Two illustrating examples are given to elucidate the solution procedure.
This study aimed to determine the antibiotic resistance and molecular epidemiology of Haemophilus influenzae isolated from children with acute respiratory infection in Chongqing, China. To this end, 1967 H. influenzae isolates from 2006 to 2009 were analysed regarding β-lactamase production and antibiotic resistance. Ninety-nine β-lactamase-producing H. influenzae isolates from 2010 were analysed for antibiotic resistance and promoter regions of bla(TEM) (-1) . β-lactamase production was found in 35.8% (705/1967) of the strains. All ninety-nine β-lactamase-producing strains from 2010 were of the TEM-1 type as determined by PCR but did not produce the predicted 1075 bp product. According to PCR-SSCP and DNA sequencing, the promoter regions of bla(TEM) (-1) were categorized into 6 genotypes as SSCP1 (Pdel), SSCP2 (Pa/Pb), SSCP3 (P4), SSCP4 (Prpt.b), SSCP5 (2Prpt) and SSCP6 (P3.b). The Pdel, Pa/Pb and Prpt.b were common promoters of bla(TEM) (-1) for H. influenzae isolated from children in Chongqing. Strains with Prpt.b were more resistant to ampicillin (AMP) than strains with Pdel, Pa/Pb and P4 (p < 0.05). Therefore, bla(TEM-1) β-lactamase is the main mechanism for resistance of H. influenzae to ampicillin in Chongqing. Furthermore, the Prpt.b promoters may be related to the high resistance of H. influenzae to AMP.
Fifty-five strains of Haemophilus influenzae recovered at a children's hospital in Korea from 1992 through 1997, were analyzed for serotype and antibiotic resistance. Antimicrobial susceptibility was tested by broth dilution method.
Among the 55 strains, 26 were from normally sterile body fluids, of which 17 were from the immunocompetent children. Spectrum in the immunocompetent included meningitis (47%), bacteremic pneumonia (18%), and bacteremia without focus (35%). Three (12%) of 26 invasive infections were caused by non-type b: one type d and two type f. Nine of 29 non-sterile body fluid isolates belonged to one of encapsulted serotypes: four a, two c, one of each of b, d and e. Thirty two (58%) strains were resistant to ampicillin, and all of which produced β-lactamase. All of the strains were highly susceptible to amoxicillin/clavulanate, cefixime, cefuroxime, azithromycin and ciprofloxacin, while 1 (2%), 7 (13%), 4 (7%) and 4 (7%) strains were intermediate to cefprozil, cefaclor, loracarbef, and clarithromycin, respectively. The serotype distribution of H. influenzae in Korean children is similar to those in developed countries before the introduction of Hib conjugate vaccine, and ampicillin resistance rate is among the highest published to date.
A beta-lactamase prevalence of 23% was found among 1,730 Haemophilus influenzae isolates. Ampicillin susceptibility was 70%, and 12% of beta-lactamase-negative strains presented diminished susceptibility to ampicillin (BLNAR phenotype). Susceptibility of 90% was found for cefaclor and clarithromycin, whereas it was nearly 100% for cefotaxime, cefixime, azithromycin, and cefuroxime. Ciprofloxacin-resistant (0.1%) and beta-lactamase-positive amoxicillin/clavulanate-resistant (BLPACR) phenotypes (0.1%) are anecdotal so far.
Haemophilus influenzae has become increasingly resistant to beta-lactam antibiotics. Three major mechanisms, both enzymatic and non-enzymatic, are involved. Enzymatic resistance is mainly due to production of a TEM-1 plasmid-mediated beta-lactamase, and in some cases to a new enzyme ROB-1. Of the non-enzymatic mechanisms, decreased permeability due to alteration of outer membrane proteins seems to be rare in comparison to decreased affinity of penicillin-binding proteins for beta-lactam antibiotics. Enzymatic resistance is present in about 10-20% of clinical isolates, while non-enzymatic resistance is present only in 2-4%.
From January 1997 to July 1999, a total of 867 isolates of Haemophilus influenzae were recovered in the microbiology laboratory of Chiba Children's Hospital. The overall prevalence of beta-lactamase production was 12.8%. Ampicillin-MICs for all of the 111 beta-lactamase-producing isolates was > or =4 microg/ml. A total of 26 beta-lactamase-negative isolates (3.4% of all beta-lactamase-negative isolates and 3.0% of all isolates) were found to be resistant to ampicillin. The prevalence of beta-lactamase negative ampicillin-resistant strains (BLNAR) increased remarkably to 8.9% during the last 7-month period. It is noteworthy that the MICs not only of penicillins but also of cephems for BLNAR were significantly higher than those for ampicillin-susceptible isolates. Eight beta-lactamase-producing isolates of H. influenzae (7.2% of all beta-lactamase-producing isolates) were resistant to amoxicillin-clavulanate (AMPC/CVA). Consequently, the overall resistance to ampicillin was 15.8%, and that to AMPC/CVA was 3.0%. The results of this study corroborate the findings of previous investigators in the US (Doern et al., 1997) regarding the emergence of BLNAR and beta-lactamase-producing AMPC/CVA-resistant strains (BLPACR) of H. influenzae. Continued monitoring of susceptibility trends will be required to guide appropriate chemotherapy.