High nasopharyngeal carriage of drug resistant Streptococcus pneumoniae and Haemophilus influenzae in North Indian schoolchildren

OBJECTIVES: To determine the carriage rate of Streptococcus pneumoniae and Haemophilus influenzae in healthy Indian schoolchildren. The prevalence of antibiotic resistant strains in the community may be used to assess the trends of antibiotic resistance in invasive strains. Prevalence of resistance to various antimicrobial drugs among S. pneumoniae and H. influenzae was estimated. METHODS: Two thousand four hundred subjects, aged 5-10 years, were enrolled from 45 rural and 45 urban schools. A nasopharyngeal swab was collected from each child, after taking informed written consent. Swabs were processed to isolate S. pneumoniae and H. influenzae. All isolates were tested for resistance to chloramphenicol, erythromycin and co-trimoxazole. Streptococcus pneumoniae isolates were also tested against tetracycline and oxacillin while H. influenzae isolates were tested against ampicillin. RESULTS: Nasopharyngeal carriage of S. pneumoniae and H. influenzae was high in healthy schoolchildren. Stratified analysis showed that nasal carriage of pneumococci in urban children was significantly lower than in rural children [46.8% vs. 53.2%, P<0.001]. Carriage rates of H. influenzae in male and female populations were significantly different (47.8% vs. 52.3%, P<0.04). Penicillin resistance in S. pneumoniae was found low (3.3%), but 22.9% of H. influenzae isolates were ampicillin resistant. Resistance to co-trimoxazole was very high in both S. pneumoniae (81.8%) and H. influenzae (67.3%). CONCLUSION: There is high nasopharyngeal carriage of drug resistant S. pneumoniae and H. influenzae in schoolchildren of north India. Currently, in India, co-trimoxazole for 5 days is recommended for treatment of non-severe pneumonia and third generation cephalosporins are drug of choice for management of severe pneumococcal/H. influenzae diseases. We found high co-trimoxazole resistance and low penicillin resistance in pneumococcal isolates. This justifies empirical use of penicillin in management of invasive pneumococcal infections in India.     

Plasmid-mediated resistance in multiply resistant Haemophilus influenzae type b causing meningitis: molecular characterization of one strain and review of the literature

The increasing prevalence of infections due to ampicillin-resistant strains of Haemophilus influenzae type b requires that suspected H. influenzae meningitis in children be initially treated with both ampicillin and chloramphenicol. Previously, the recognition of strains resistant to chloramphenicol but susceptible to ampicillin supported combination chemotherapy. In this study one case of meningitis due to a strain of H. influenzae resistant to ampicillin, chloramphenicol, and tetracycline was analyzed. The patient involved received intravenous trimethoprim-sulfamethoxazole, but putative resistance to this combination prompted the additional administration of intravenous moxalactam. The resistance of this organism was mediated by a conjugative 43-megadalton R plasmid; the determinants of ampicillin and chloramphenicol resistance were transferred as a single unit. However, not all of the multiply resistant transconjugants contained a detectable plasmid; DNA homology studies with R plasmids of H. influenzae confirmed that these extrachromosomal DNA sequences were associated with chromosomal DNA and that an extrachromosomal location was rare.     

Antimicrobial resistance of Haemophilus species in patients with chronic bronchitis.

Haemophilus influenzae strains resistant to ampicillin have become an important cause of disease in pediatric patients. Because many adults with chronic bronchitis carry Haemophilus organisms in their tracheobronchial tree and because antimicrobial agents are used commonly in these patients, we assessed the prevalence of resistance to ampicillin and other antimicrobial agents in this population. We studied 150 Haemophilus isolates (73 H. influenzae, 69 H. parainfluenzae, 6 H. parahemolyticus, and 2 H. hemolyticus) obtained from 138 patients with chronic bronchitis from January 1978 through March 1979. Ampicillin resistance due to production of beta-lactamase was found in 7 of the 150 isolates (4.7 %)-2 H. influenzae, 4 H. parainfluenzae and 1 H. parahemolyticus. Resistance to tetracycline was found in 9 strains (6 %), but all strains were susceptible to chloramphenicol.     

Ampicillin, tetracycline, and chloramphenicol resistant Haemophilus influenzae in adults with chronic lung disease. Relationship of resistance to prior antimicrobial therapy

Antibiotic resistance in 1,003 sputum isolates of Haemophilus influenzae from adults with chronic lung disease was assessed from January 1983 through June 1986. The incidence of resistance was 3.2% for tetracycline, 0.6% for chloramphenicol, and 12.5% for ampicillin. Resistance to ampicillin or tetracycline usually occurred alone, while 100% of chloramphenicol resistant isolates were co-resistant to tetracycline or ampicillin. More than 90% of antibiotic resistant isolates were nontypable and belonged to biotypes II, III, or V. Chart reviews of 331 patients revealed that patients with ampicillin resistant isolates were more likely than control subjects to have received ampicillin in the prior 6 wk (33% versus 6%, p less than 0.0001), whereas patients with isolates resistant to tetracycline or chloramphenicol plus tetracycline were more likely to have received tetracycline than control subjects (24% and 50%, respectively, versus 5%, p less than 0.005). The incidence of ampicillin resistance and the reluctance of physicians caring for adults to use chloramphenicol suggests that a newer cephalosporin such as cefotaxime may be the initial therapy of choice for severe H. influenzae disease in our patient population.     

Relapse of acute purulent otitis media: antibiotic sensitivities of nasopharyngeal pathogens

The present investigation was conducted to find out if a relapse of acute purulent otitis media is associated with a decreased sensitivity of nasopharyngeal pathogens to commonly used antimicrobial agents. All but one of 63 children with relapse included in this study yielded one or more of the classical middle ear pathogens (Streptococcus pneumoniae, Haemophilus influenzae, Branhamella catarrhalis, S. pyogenes) in their nasopharynx (NPH) secretions. S. pneumoniae was the predominating isolate from NPH (71% of the patients) as well as from middle ear effusion (53%). At a control visit 4 weeks after the start of antibiotic therapy, 91% were NPH carriers of potential pathogens and S. pneumoniae was still the most common isolate (53%). Beta-lactamase was produced by 55% of B. catarrhalis isolates from the NPH specimens on the first visit, but only by 33% of B. catarrhalis isolates on the control visit. Two NPH isolates of H. influenzae produced beta-lactamase. One isolate of S. pneumoniae (serotype 18) was intermediately sensitive to phenoxymethylpenicillin. Generally low MICs were found for erythromycin and cefaclor. H. influenzae isolates were generally sensitive to ampicillin in vitro, but only 1 isolate was fully sensitive to erythromycin. B. catarrhalis isolates were uniformly sensitive to doxycycline and trimethoprim/sulphamethoxazole. No tolerance to penicillin was demonstrated in S. pneumoniae and H. influenzae. The present data indicate that the relapse of acute otitis media is not associated with development of tolerance or resistance to therapeutic antimicrobials commonly used.     

Clinical effects of piperacillin and tazobactam/piperacillin on Haemophilus influenzae lower respiratory tract infection in pediatric patients

OBJECTIVE: The prevalence of beta-lactamase-nonproducing ampicillin-resistant (BLNAR) Haemophilus influenzae (H. influenzae) has been increasing in recent years. Piperacillin (PIPC) is one of a few beta-lactams possessing good activity against BLNAR H. influenzae. We studied clinical efficacy of piperacillin and its beta-lactamase inhibitor, tazobactam/piperacillin (TAZ/PIPC) in children with lower respiratory tract infection caused by H. influenzae including resistance strains. METHODS: Subjects were 20 children with lower respiratory tract infection caused by H. influenzae treated with PIPC 100mg/kg/day (7 cases) or TAZ/PIPC 125mg/kg/day (13 cases). We selected cases from which resistant H. influenzae strains might be detected. Patients received prior antimicrobial therapy within two weeks before admission, or with underlying diseases. We examined patient profiles, clinical efficacy, susceptibilities for 6 beta-lactam antibiotics [PIPC, TAZ/PIPC, ampicillin (ABPC), cefotaxime (CTX), ceftriaxone (CTRX), and meropenem (MEPM)] and analyzed 6 genotype patterns of beta-lactam resistant genes by PCR. RESULTS: Efficacy was 7/7 in patients in PIPC group and 12/13 in patients in TAZ/PIPC group. Diminished efficacy was seen in only one case complicated with severe RSV infection. The susceptibility of all strains but one beta-lactamase producing, ABPC resistant (BLP) strain to PIPC and of all to TAZ/ PIPC was below 0.25 microg/mL. The genotype of the 15 strains isolated from the sputum on administration was as follows; beta-lactamase nonproducing, ABPC-susceptible (gBLNAS) strains were 4, gBLP strain was 1, beta-lactamase nonproducing, and ABPC-resistant (gLow-BLNAR) strains were 2, beta-lactamase nonproducing, ABPC resistant (gBLNAR) strains were 8. CONCLUSION: PIPC and TAZ/PIPC were useful against lower respiratory tract infection caused by H. influenzae including BLNAR in children.     

The prevalence of beta-lactamase negative ampicillin resistant Haemophilus influenzae in Mie Prefecture

Equivalent MIC breakpoints to detect beta-lactamase negative ampicillin resistant Haemophilus influenzae (BLNAR) were controversial. We studied the relationship of drug resistance with gene alterations in 74 clinical isolates of H. influenzae. Out of 74 isolates, 26 showed MIC of ampicillin (ABPC) > or = 1 microg/ml. All isolates, except one, with MIC of ABPC > or = 4 microg/ml were found to produce beta-lactamase, while all 19 isolates with MIC of ABPC at 1 or 2 microg/ml were non-producing. Twenty-six ABPC resistant isolates were subjected to the analysis of genes involved in the drug resistance such as pbp3-1 pbp3-2, and TEM by the Haemophilus influenzae gene detection kit (Wakunaga Pharmaceutical Co., Ltd.) according to the supplier's instructions. Three (21.4%) of 14 beta-lactamase non-producing isolates with ABPC-MIC of 1 microg/ml had mutations of pbp3-1 gene, while all 5 non-producing isolates with ABPC-MIC of 2 microg/ml showed mutations of both pbp3-1 and pbp3-2 genes. Accordingly, it seems appropriate to set ABPC-MIC > or = 2 microg/ml for detection of BLNAR. In this study, six (8.1%) of 74 isolates were found to be BLNAR, and all of these six isolates were derived from patients of 5 year-old or younger.     

Antimicrobial susceptibilities of Haemophilus species in Hong Kong

Altogether 403 Haemophilus spp. were isolated in seven hospital laboratories in Hong Kong during June 1986, mostly from sputum. Of these 73% were Haemophilus influenzae and 27% Haemophilus parainfluenzae. All the isolates of H. influenzae were non-capsulated; Haemophilus spp. were not isolated from blood or cerebrospinal fluid (CSF) during the period of the study. Antimicrobial resistance, including multiple resistance, was common. Of all the strains of H. influenzae, 20% were resistant to 1 mg/l ampicillin, (all except one by production of TEM-1 beta-lactamase), 65% were resistant to 0.5 mg/l erythromycin, 25% to 1 mg/l tetracycline, 14% to 1 mg/l chloramphenicol (mediated by the production of a chloramphenicol-destroying enzyme) and less than 1% to 8 mg/l cefaclor and 0.5 mg/l trimethoprim. All isolates were susceptible to cephamandole and cefuroxime. Haemophilus parainfluenzae showed similar susceptibilities, except that a greater proportion of strains was sensitive to erythromycin and chloramphenicol. Only 50% of the ampicillin-resistant strains of H. influenzae and H. parainfluenzae contained detectable plasmids of 2-55 Mdal arranged in six to nine different plasmid profiles. Resistance to ampicillin and chloramphenicol has increased markedly in isolates of H. influenzae in Hong Kong over the last 5 years. This resistance may be associated with transposable genes.     

Emergence of resistance to imipenem during therapy for Pseudomonas aeruginosa infections

We studied the mechanism of resistance to imipenem in three clinical isolates of Pseudomonas aeruginosa. Two of these isolates arose from imipenem-susceptible strains isolated during therapy with imipenem and were associated with treatment failure. One of these two strains had previously been broadly resistant to beta-lactams; the second acquired resistance to imipenem alone. One isolate of the third strain was resistant to imipenem but susceptible to other antipseudomonal beta-lactams. No isolate contained beta-lactamase activity capable of hydrolyzing imipenem at a detectable rate. Studies of the penicillin-binding proteins of all isolates revealed no differences in the number of proteins, molecular weight of, affinity for penicillin, or affinity for imipenem in any isolate. In each case the resistant isolate lacked one or more outer membrane proteins that were present in a susceptible isolate of the same strain. The observed alterations in outer membrane proteins may be associated with diminished permeability of the bacterial outer membrane to imipenem and may be the major factor responsible for resistance in these isolates.     

Prevalence of and detection of resistance to ampicillin and other beta-lactam antibiotics in Haemophilus influenzae in Denmark

The susceptibility of Haemophilus influenzae to penicillin V and G, ampicillin and cefuroxime was investigated by MIC, disc and tablet diffusion methods, using chocolate agar as test medium, to determine the prevalence of ampicillin-resistant isolates and the optimal method for their detection. Eighty-six isolates were clinical isolates collected prospectively from July to September 1998 and 22 isolates were clinical isolates with decreased susceptibility to ampicillin previously referred to the reference laboratory. Eighty-seven isolates were ampicillin-susceptible and 16 were ampicillin-resistant. Thirteen produced beta-lactamases. Among the consecutive isolates 12.8% were resistant. With each of the Rosco Neo-sensitabs containing penicillin G, 2.5 microg ampicillin and 33 microg ampicillin, 3 very major errors occurred (resistant isolates misinterpreted as susceptible) and 5-13 major errors (susceptible isolates misinterpreted as resistant). The AB biodisk containing ampicillin (10 microg) was superior to the penicillin V and G discs, i.e. only 1 very major error occurred and major and minor errors were infrequent. The cefuroxime disc identified 4/8 beta-lactamase-negative ampicillin-resistant isolates. Thus, for susceptibility testing with chocolate agar as test medium, the use of an inoculum of 10(5) colony-forming units, 10 microg ampicillin discs and interpretative zone diameters of > or = 28 mm indicating susceptibility and < or = 25 mm indicating resistance was found to produce reliable identification of ampicillin-resistant isolates of H. influenzae.     

Streptococcus pneumoniae carriage and penicillin/ ceftriaxone resistance in hospitalised children in Darwin

Background: The prevalence of resistant Streptococcus pneumoniae (SP) is increasing worldwide. Pneumococcal prevalence and susceptibility patterns are not known for children in the Top End of the Northern Territory.
Aims: To determine the prevalence of nasopharyngeal carriage of pneumococci in children hospitalised in Darwin, and the extent of penicillin and ceftriaxone resistance in these isolates.
Methods: Nasopharyngeal swabs were collected on admission from 85 children who had not received antimicrobials for their admission illness. Antimicrobial resistance was determined following selective culture for SP isolates. Minimal inhibitory concentrations (MICs) for penicillin and ceftriaxone were determined using the E-test method.
Results: The overall prevalence of nasopharyngeal SP carriage was 44%. Carriage occurred more often in Aboriginal children from rural areas (56%) than in urban children (24%) (OR 3.94, 95% CI 1.35 - 11.78, p <0.01). Thirty per cent of isolates were penicillin resistant, 35% were ceftriaxone resistant, and 49% were resistant to at least one of these. One isolate showed high-level resistance to both antimicrobials; all other resistant isolates were of intermediate-level resistance. For the same isolate, MICs for ceftriaxone were more often higher than those for penicillin. Five isolates had intermediate resistance to ceftriaxone whilst remaining sensitive to penicillin.
Conclusions: The prevalence of pneumococcal resistance to penicillin and ceftriaxone in hospitalised children in Darwin is much higher than previously reported in Australia. This has implications for future antimicrobial management and highlights the need for regular regional surveillance of SP resistance. The development of conjugate pneumococcal vaccines for children under two years is a priority.     

临床分离流感嗜血杆菌和副流感嗜血杆菌的耐药性研究

目的 了解上海部分医院分离的流感和副流感嗜血杆菌对常用抗菌药物的敏感性、对β内酰胺类和喹诺酮类药物的耐药机制以及耐药菌株的克隆传播情况.方法 以琼脂稀释法测定氨苄西林等13种抗菌药物对2006年上海5所医院临床分离的156株嗜血杆菌属细菌的体外抗菌活性,头孢硝噻吩纸片法检测β-内酰胺酶,PCR扩增检测TEM和ROB型β-内酰胺酶基因和喹诺酮类耐药株的喹诺酮耐药决定区,以肠杆菌科基因间重复序列聚合酶链反应(ERIC-PCR)比较细菌的同源性.药物敏感性试验结果采用χ2检验,ERIC-PCR条带模型转换数据进行聚类分析.结果 109株流感嗜血杆菌对氨苄西林敏感率为74.3%,而对氨苄西林舒巴坦、头孢菌素类、氟喹诺酮类等敏感率为100.0%.109株流感嗜血杆菌和47株副流感嗜血杆菌β-内酰胺酶产酶率分别为25.7%和19.1%(χ2=0.776,P=0.378),产酶株均检测到TEM基因.109株流感嗜血杆菌中仅1株对环丙沙星耐药,其gyrA基因存在84位丝氨酸突变为亮氨酸,parC基因存在206位甘氨酸突变为精氨酸.ERIC-PCR结果显示,106株流感嗜血杆菌在85%相似度水平可被分为73型.结论 上海地区流感嗜血杆菌临床菌株对除氨苄西林外的其他常用抗菌药物仍保持很高的敏感率.受试流感嗜血杆菌对氨苄西林耐药的主要机制均为产TEM型β-内酰胺酶.在包括氨苄西林耐药株在内的流感嗜血杆菌中,克隆传播尚不普遍.     

Biotyping, capsular typing, and antibiotic resistance pattern of Haemophilus influenzae strains in Iran

The aim of this study was to determine the capsular types of Haemophilus influenzae isolated from clinical specimens by slide agglutination serotyping (SAST) and PCR capsule typing methods. All the isolates were biotyped and their antibiotic resistance patterns also determined. Thirteen isolates of serotype b, 2 of serotype e, 4 of serotype f, and 19 nontypeable (NT) isolates were identified by SAST method in 38 H. influenzae culture-positive samples. Capsule typing by PCR increased the proportion of all invasive cases from 34.2% (by SAST) to 60.5%, and 6 culture-negative samples were identified as invasive H. influenzae (Hib) by this method. The discrepancy rate between SAST and PCR results were 41%. Biotypes I, II, and III were the prevalent biotypes whereas biotypes VI and VII were not found. The majority of capsule type b belonged to biotype II. The isolates were resistant to cotrimoxazole (47.1%) and ampicillin (43.6%). Multidrug resistance was observed in 7 of the isolates.     

Host risk factors for acquirement of antimicromial resistant gene in Haemophilus influenzae

The present study investigated the host risk factors for carriage of Haemophilus influenzae (H. influenzae) with resistant gene (s) against antibiotics. From September 2001 to January 2004, 174 strains of H. influenzae were isolated from the nasopharynx of children with respiratory tract infections. We classified these strains on the basis of the MIC to Ampicillin and the presence of resistant gene (s) for antibiotics resistance (gene for beta-lactams and altered pbp gene (s)). The patients' background such as previous antibiotic usage, age, daycare attendance, siblings and underlying diseases was investigated. The risk factor for carriage of strains with altered pbp gene (s) was the usage of beta-lactams within the last 3 months. Controlled usage of oral beta-lactams might be an important issue for preventing the spread of resistant H. influenzae strains such as beta-lactamase non-producing ampicillin resistant H. influenzae. We have to reconsider a therapeutic approach for the treatment of young children with respiratory tract infection.     

Five-year study of antimicrobial susceptibility and beta-lactamase production in Haemophilus influenzae

We evaluated 582 Haemophilus influenzae isolates from patients between January 2000 and December 2004. Overall, 433 isolates were obtained from sputum and bronchial washings, 124 isolates were from pus, 19 isolates were from blood and 6 isolates form cerebrospinal fluid. H. influenzae was sensitive to amoxicillin/clavulanate, ampicillin/sulbactam, gentamicin, cefuroxime, ceftriaxone, cefotaxime, ciprofloxacin, ofloxacin, imipenem, meropenem (range 97-100%), chloramphenicol (75%), ampicillin/amoxicillin (52%), but resistant to trimethoprim-sulphamethoxazole. As for beta-lactamase production, 48.4% of the isolates tested were positive.     

Invasion of the inner ear by Haemophilus influenzae type b in experimental meningitis

Bacterial interstrain variation for cochlear invasion was studied by intraperitoneal inoculation of infant rats with Haemophilus influenzae type b. Eight pairs of CSF isolates from children with or without deafness due to meningitis were injected into half of each litter in separate experiments. At 48 h, quantitative CSF culture results and CSF white blood cell counts were equivalent for the two groups. Organisms within the cochlea were detected in four of eight animals in each group. There was no difference between the deaf and nondeaf isolates in the degree or frequency of inner ear inflammation in formalin-fixed sections. In separate experiments, animals were inoculated with H. influenzae type b and 24 h later treated with ampicillin, or ampicillin plus dexamethasone. At 48 h, although CSF white blood cell counts were significantly reduced in the steroid group, no difference was noted in the degree of cochlear inflammation between the two groups. The ability of H. influenzae type b to invade the inner ear of infant rats does not correlate with the development of sensorineural deafness in children following H. influenzae type b meningitis. Steroid administration does not appear to diminish the inflammatory reaction within the cochlea more than antibiotics alone in this model, but may delay CSF sterilization by ampicillin.     

Pneumococcal and Haemophilus influenzae meningitis in a children's hospital in Ethiopia: serotypes and susceptibility patterns

Streptococcus pneumoniae and Haemophilus influenzae are responsible for most pyogenic meningitis cases in children in Ethiopia. Resistance of S. pneumoniae and H. influenzae to penicillin and chloramphenicol respectively has been reported globally. Resistance has been related to specific serotypes of S. pneumoniae or to beta-lactamase-producing H. influenzae strains. This study describes the serotypes/ serogroups and susceptibility pattern of the two organisms causing meningitis in Ethiopian children. There were 120 cases of meningitis caused by S. pneumoniae (46) and H. influenzae (74) over a period of 3 years (1993-95). Nineteen children died from pneumococcal and 28 from haemophilus meningitis. Penicillin-resistant pneumococcal meningitis (4/8 = 50%) caused a greater mortality rate than penicillin-susceptible pneumococcal meningitis (15/38 = 39%). Common serotypes accounting for 76% of S. pneumoniae were type 14, 19F, 20, 1, 18 and 5; and serotypes 14, 19F and 7 (accounting for 17% of strains) showed intermediate resistance to penicillin G. 97% of the H. influenzae isolates were type b, and in only two cases beta-lactamase-producing. 72% of isolates of the S. pneumoniae we identified belong to serotypes preventable by a 9-valent vaccine. Our study highlights the possibility of resistant pyogenic meningitis in children in Ethiopia due to emerging resistant strains of S. pneumoniae and H. influenzae isolates.     

Children with trimethoprim- and ampicillin-resistant fecal Escherichia coli in day care centers

We conducted a cross-sectional study of 79 children attending seven day care centers in Houston, Texas, to detect fecal gram-negative bacilli resistant to trimethoprim (TMPr) and ampicillin (AMPr). Fifteen children (19%) were colonized with TMPr Escherichia coli; all but one strain were also resistant to sulfonamides. Most of the children with TMPr E. coli were clustered in center A, where 11 (37%) of 30 children were colonized; only four (8%) of 49 children in the other six centers were colonized with TMPr E. coli (P less than .005). The TMPr E. coli isolates from 10 of the 11 children in Center A had a similar antibiogram, which included resistance to sulfonamides, ampicillin, and streptomycin; eight had a similar total plasmid pattern, an observation suggesting spread within the day care center. Children colonized with AMPr E. coli were present in all centers, although a higher percentage of children in center A were colonized than in the other centers combined (70% vs. 35%; P less than .01).     

Invasive Haemophilus influenzae disease in adults

In a five-year period, 29 cases of bacteremia and/or meningitis in adults caused by Haemophilus influenzae were seen in our large community hospital. There were 17 cases of bacteremic pneumonia and 12 cases of serious extrapulmonary infections. The extrapulmonary infections included cases of endocarditis, meningitis, cholecystitis, epiglottitis, tubo-ovarian abscess, and cellulitis. In contrast with the pediatric experience, H influenzae type B was the causative pathogen in only 45% of patients and only one isolate was ampicillin resistant.