Penicillin-intermediate S. Pneumoniae Research Articles

Comparative Bactericidal Activity of three Fluoroquinolones against Streptococcus pneumoniae and Hemophilus influenzae isolated from Acute Bacterial Rhinosinusitis

Background: Recently, the most common bacteriae in acute bacterial rhinosinusitis (ABRS), Streptococcus pneumoniae and Hemophilus influenzae, have acquired various degrees of resistance to many traditional antibiotics. Methods: We evaluated the bactericidal activity of three new fluoroquinolones, levofloxacin (LVFX), garenoxacin (GRNX), and sitafloxacin (STFX), against current isolates of S. pneumoniae (50 strains) and H. influenzae (50 strains) from patients with ABRS in Japan. Results: No fluoroquinolone-resistant penicillin-susceptible S. pneumoniae (PSSP) strains were detected. The MIC of PSSP for both GRNX and STFX were . 0,06 ƒEg/ml, whereas that for LVFX was significantly elevated as compared with those of GRNX and STFX. One strain of penicillin-intermediate S. pneumoniae (PISP) was an LVFX-resistant strain. A significant elevation of MIC of PISP was observed in LVFX as compared with GRNX and STFX. There were no strains of S. pneumonia with resistance to the three fluoroquinolones. All of the H. influenzae strains showed excellent sensitivity to all three fluoroquinolones. Conclusions: Although LVFX-resistant S. pneumoniae was found in this study, the strong potency of GRNX and STFX against S. pneumoniae and H. influenzae suggests the use of antibiotics is appropriate in severe cases of ABRS.

新潟県長岡地区の基幹病院における肺炎球菌, インフルエンザ菌, 緑膿菌の検出状況と抗生物質に対する感受性の検討 (3年間の年次推移)

We measured MICs of various antimicrobial agents against Streptococcus pneumoniae, Haemophilus influenzae, and Pseudomonas aeruginosa isolated in the Nagaoka district of Niigata Prefecture in 2000 (March-May), 2001 (January-May), and 2002 (March-May). S. pneumoniae: Fifty-six strains were isolated in 2000, 119 strains in 2001, and 88 strains in 2002. In 2000, 2001, and 2002, 24 strains (42.9%), 58 strains (48.7%), and 40 strains (45.5%), respectively, were penicillin-intermediate S. pneumoniae (PISP), and 4 strains (7.1%), 12 strains (10.1%), and 7 strains (8.0%), respectively, were penicillin-resistant S. pneumoniae (PRSP). Carbapenems had the most excellent antimicrobial activity, followed by penicillin G, against penicillin-susceptible S. pneumoniae (PSSP), PISP, and PRSP. H. influenzae: Seventy-six strains were isolated in 2000, 154 strains in 2001, and 91 strains in 2002. In 2000, 2001, and 2002, 6 strains (7.9%), 8 strains (5.2%), and 7 strains (7.7%), respectively, were beta-lactamase-producing ampicillin (ABPC)-resistant strains (MIC > or = 2 micrograms/ml), showing no increase, and 14 strains (18.4%), 70 strains (45.5%), and 31 strains (34.1%), respectively, were beta-lactamase-non-producing ABPC-resistant strains (MIC > or = 2 micrograms/ml), showing a slight increase. Ceftriaxon, meropenem (MEPM), and levofloxacin had excellent antimicrobial activity against these resistant strains. P. aeruginosa: In 2000, 2001, and 2002, 135, 74, and 91 strains, respectively, were isolated, and 14 strains (10.4%), 17 strains (23.0%), and 24 strains (26.4%), respectively, were imipenem-resistant (MIC > or = 16 micrograms/ml), showing a slight increase. MEPM, biapenem, and ciprofloxacin had excellent antimicrobial activity against P. aeruginosa.

長野県下の基幹病院における肺炎球菌, インフルエンザ菌, 緑膿菌の分離状況と各薬剤感受性の検討

We determined the minimum inhibitory concentration (MIC) of various antimicrobial agents against 140 strains of Streptococcus pneumoniae, 131 strains of Haemophilus influenzae and 178 strains of Pseudomonas aeruginosa isolated from respiratory organs in 28 affiliated hospitals in Nagano prefecture between December 2002 and February 2003. The results of this report were as followed: 1. All 140 strains of S. pneumoniae were classified into 3 groups; penicillin-susceptible S. pneumoniae (PSSP) (47.1%), penicillin-intermediate S. pneumoniae (PISP) (43.6%) and penicillin-resistant S. pneumoniae (PRSP) (9.3%). 2. Carbapenems and glycopeptide (vancomycin) had highly potent antimicrobial activity against PISP and PRSP like PSSP. However, some of PISP or PRSP isolates were resistant to cephalosporins and a fluoroquinolone (levofloxacin). 3. All 131 strains ofH. Influenzae were also classified into three groups; ampicillin sensitive H. influenzae (73.3%), beta-lactamase producing ampicillin resistant H. influenzae (BLPAR) (8.4%) and beta-lactamase negative ampicillin resistant H. influenzae (BLNAR) (18.3%). 4. Carbapenems and a fluoroquinolone had highly potent antimicrobial activity against BLPAR and BLNAR. However, there were clear differences among 4 carbapenems for the antimicrobial activity. Ceftriaxone (CTRX) was the most active among cepharosporins in this study. 5. The rate of P. aeruginosa isolates resistant to carbapenems, a fluoroquinolone and aminoglycosides were about 11 to approximately 16%, 15% and 0.6 to approximately 8%, respectively. None of the strains was resistant to all 3 antimicrobial classes, but 3 strains were resistant to combination of 2 classes. 6. The MIC50 and MIC90 values of various antibiotics against S. pneumoniae, H. influenzae and P. aeruginosa were different in all 4 regions. In conclusion, the antimicrobial surveillance programs are important for guiding empiric therapy and for focusing interventional control of antimicrobial resistance in regions and hospitals.

Nationwide survey of the development of drug-resistant pathogens in the pediatric field in 2007 and 2010: drug sensitivity of Streptococcus pneumoniae in Japan (second report).

We previously conducted nationwide surveillance of Streptococcus pneumoniae in 2000–2001 (period 1) and 2004 (period 2) and reported the findings. Subsequent surveillance surveys conducted in 2007 (period 3) and 2010 (period 4) are now reported. Bacterial strains were clinically isolated from children with meningitis, sepsis, and respiratory tract infections at 27 hospitals participating in the Drug-Resistant Pathogen Surveillance Group in Pediatric Infectious Disease. Twenty-one drugs were investigated for 283 isolated strains in period 3, and 24 drugs were investigated for 459 strains in period 4. In period 3, 43.8 % of strains were penicillin-susceptible S. pneumoniae (PSSP), 52.3 % were penicillin-intermediate S. pneumoniae (PISP), and 3.9 % were penicillin-resistant S. pneumoniae (PRSP). In period 4, the percentages were PSSP 23.1 %, PISP 49.9 %, and PRSP 27.0 %. The resistance rates were 56.2 % and 76.9 %, respectively. Drug sensitivity was best with panipenem, at a minimum inhibitory concentration (MIC)90 ≤0.063 μg/ml in period 3, and with tebipenem (MIC90 ≤ 0.063 μg/ml) in period 4. Patients’ background factors related to increased bacterial resistance were investigated, and significant differences were found depending on whether a child had siblings (P = 0.0056) or was a daycare center attendee (P = 0.0195) in period 3, and age category (P = 0.0256) in period 4. No factors were common to both periods 3 and 4. Pneumococcus is a major causative organism of pediatric infectious disease, and we plan to continue conducting surveillance and providing information in the future.

Antimicrobial susceptibility of community-acquired respiratory tract pathogens isolated from adults in China during 2009 and 2010

To investigate the drug-resistance rates of community-acquired respiratory tract pathogens isolated from adults in China during 2009 and 2010. A total of 1793 strains (S. aureus 421, S. pneumoniae 420, K. pneumoniae 404, H. influenzae 313, other Streptococcus. spp 149, and M. catarrhalis 86) of non-duplicated community-acquired respiratory tract pathogens were isolated from 11 hospitals in 6 cities. The MIC values were determined by the broth microdilution method, and the production of β-lactamase was tested using a nitrocefin-based test. All of the S.aureus isolates were methicillin-sensitive (MSSA). Of the MSSA isolates, less than 1% (4/421) was resistant to β-lactamase inhibitor combinations, about 13.1% (55/421) and 9% (38/421) resistant to levofloxacin and moxifloxacin, and 57% (240/421), 53.2% (224/421), and 88.7% (373/421) resistant to azithromycin, clarithromycin, and penicillin, respectively. No S. aureus isolates resistant to vancomycin were detected in this study. Based on different criteria, the percentages of penicillin-sensitive S. pneumoniae (PSSP), penicillin-intermediate S. pneumoniae (PISP), and penicillin-resistant S. pneumoniae (PRSP) were 24.4% (102/420), 27.3% (115/420), 48.3% (203/420) (Oral) and 1.9% (8/420), 9% (38/420), 89.1% (374/420) (parenteral), respectively. The resistance rates of S. pneumonia to azithromycin, clarithromycin, cefaclor, cefuroxime, ceftriaxone and amoxicillin with clavulanic acid were 88.2% (370/420), 87.4% (367/420), 45.3% (190/420), 41.9% (176/420), 10.2% (43/420), and 5.2% (22/420), respectively. About 2.6% (11/420) and 0.2% (1/420) of S. pneumonia isolates were resistant to levofloxacin and moxifloxacin. More than 70% (104/149) of β-hemolytic streptococci isolates were resistant to azithromycin and clarithromycin, and about 10.1% (15/149) of isolates were resistant to levofloxacin. The resistance rates of K.pneumonia to most antibiotics were > 20% (81/404), and that of ceftazidime was lower than cefuroxime, cefaclor, and ceftriaxone. The mean prevalence value of ESBL producing K. pneumonia was 38.8% (157/404), with significantly regional variations. More than 90% of H. influenza and M. catarrhalis were susceptible to most antibiotics, with resistance rate of < 5% (16/313, H. influenza; 4/86, M. catarrhalis). The mean productions of β-lactamase in H. influenza and M. catarrhalis were 13.1% (41/313) and 91.7% (79/86), respectively. The percentage of PRSP increased significantly, and the resistance rates of community-acquired respiratory tract pathogens to common antibiotics such as macrolide and cephalosporins increased gradually. New fluoroquinolones such as moxifloxacin showed a high antimicrobial activity against most of the respiratory pathogens.

Resistance study of community respiratory pathogens isolated in China from 2005 to 2007

To investigate the antimicrobial resistance of community respiratory pathogens isolated in China. The strains of Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, S. pyogenes were isolated from patients with community-acquired respiratory tract infections at 14 Chinese hospitals from 2005 to 2007. Etest and disk diffusion methods were used to survey the susceptibility of 14 antibiotics against these strains. These antibiotics included penicillin G, ampicillin, amoxicillin/clavulanic acid, cefaclor, cefprozil, ceftriaxone, cefepime, levofloxacin, gatifloxacin, ciprofloxacin, tetracycline, clindamycin, erythromycin and trimethoprim/sulfamethoxazole (SXT). A total of 1870 strains were collected including S. pneumoniae (n = 997), S. pyogenes (n = 176), H. influenzae (n = 499) and M. catarrhalis (n = 198). The 2005 - 2007 prevalence of penicillin-susceptible S. pneumoniae (PSSP) were 92.6%, 73.9%, 74.1% and penicillin-intermediate S. pneumoniae (PISP) 4.5%, 9.5%, 14.3% and penicillin-resistant S. pneumoniae (PRSP) 2.9%, 16.6%, 11.6% respectively. 36.9% of S. pneumoniae strains isolated from <or= 6 years old children were penicillin-non-susceptive isolates (PNSSP) and < 22.0% of PNSSP isolated from other age groups. The susceptible rates of beta-lactamase antibiotics to PRSP and PISP isolates were less than 25.0% and 49.2% respectively. From 48.5% to 98.6% PSSP isolates were susceptible to beta-lactamase antibiotics. The susceptible rates of PNSSP and PSSP to erythromycin, tetracycline and SXT were below 7.1% and 32.1% respectively. About 95% S. pneumoniae were susceptible to ciprofloxacin, levofloxacin and gatifloxacin. All of S. pyogenes isolates were susceptible to beta-lactamase antibiotics, and 16.7%, 27.1% and 15.6% Of S. pyogenes isolates were susceptible to erythromycin. 8.5%, 19.9%, 15.3% of H. influenzae and 57.4%, 78.8%, 95.5% of M. catarrhalis produced beta-lactamase during the 3-year period. The susceptible rates of cefepime, ceftriaxone, gatifloxacin, levofloxacin and ciprofloxacin to H. influenzae and M. catarrhalis were >or= 92.9%. Antimicrobial resistance in S. pneumoniae is rising. The prevalence of PNSSP isolated from children < or = 6 years old is higher than other age groups. Amoxicillin-clavulanic acid, ceftriaxone, cefepime, gatifloxacin and levofloxacin remain highly active against common community respiratory pathogens.

1997 年から2006 年までに分離されたインフルエンザ菌， 肺炎球菌の薬剤耐性推移

We studied changes in the drug resistance of 606 strains of Haemophilus influenzae (H. influenzae) and 502 strains of Streptococcus pneumoniae (S. pneumoniae) isolated from our patients between 1997 and 2006. The incidence of beta-lactamase nonproducing ampicillin-susceptible H. influenzae (BLNAS) in 1997-1998 and 1999-2000 was 72.0 and 69.6%, respectively. In 2005-2006, the incidence of BLNAS decreased to 31.0%, while that of beta-lactamase nonproducing ampicillin-resistant H. influenzae (BLNAR) and intermediate-resistant H. influenzae increased to 65.5%. Remarkably early development of BLNAR and intermediate-resistant H. influenzae was found in patients younger than 3 years, as compared to patients older than 3 years. The proportion of penicillin-susceptible S. pneumoniae (PSSP) in 1999-2000 was 18.4%. In 2005-2006, the proportions of penicillin-resistant S. pneumoniae (PRSP) and penicillin-intermediate S. pneumoniae (PISP) were lower, while that of PSSP increased to 38.2%. An early increase in the proportion of PSSP was found in patients older than 3 years, as compared to patients younger than 3 years. The difference between age groups may be attributed to entrance into nursery school, frequent administration of antibiotics, and the immature immunological state of patients younger than 3 years. Therefore, changes in the drug resistance of H. influenzae and S. pneumoniae should be investigated separately, depending on the age of the patients. The minimum inhibitory concentrations of antibiotics, including cefditoren and cefcapene, against BLNAR and PRSP did not increase. The marked increase in intermediate-resistant H. influenzae and BLNAR mandates a re-evaluation of the directions for antibacterial agents.

A trimer of phenoxymethyl penicillin sulphone: synthesis of a new beta-lactam podand.

We determined the minimum inhibitory concentration (MIC) of various antimicrobial agents against 108 strains of Streptococcus pneumoniae and 144 strains of Haemophilus influenzae isolated from respiratory organs in the First Department of Internal Medicine, Shinshu University, and affiliated hospitals between January 2000 and February 2001. The following results were obtained. 1. Fifty-one (47.2%), 56 (51.9%), and 1 (0.9%) of 108 strains of S. pneumoniae were classified as penicillin-susceptible S. pneumoniae (PSSP), penicillin-intermediate S. pneumoniae (PISP), and penicillin-resistant S. pneumoniae (PRSP), respectively. 2. Three carbapenems had potent antimicrobial activity against PISP and PRSP. Furthermore, none of the strains were highly resistant (MIC > 2 micrograms/ml) to benzylpenicillin, ampicillin (ABPC), sulbactam/ampicillin (SBT/ABPC), cefotaxime (CTX), or cefepime (CFPM). 3. Eleven (7.6%) and 6 (4.2%) of 144 strains of H. influenzae were classified as beta-lactamase-producing ABPC-resistant strains and beta-lactamase negative ABPC-resistant H. influenzae (BLNAR), respectively. Levofloxacin, sulfamethoxazole/trimethoprim, and meropenem had potent antimicrobial activity against these resistant strains. 4. BLNAR strains were more highly resistant to CTX, CFPM, SBT/ABPC, and cefaclor than beta-lactamaseproducing strains. 5. In our surveillance study regarding clinical isolates of S. pneumoniae and H. influenzae from respiratory organs in Nagano prefecture, there were regional differences in the isolation rate and antimicrobial susceptibility. The isolation rates of resistant strains were lower than those reported in a nationwide survey.

Resistance to antimicrobiotics and mutation of PBPs in Streptococcus pneumoniae isolated from Kinki region of Japan

We studied the susceptibility to penicillin G (PCG) and other antimicrobiotics in 235 clinical isolates of Streptococcus pneumoniae. Samples were collected between April 1 and June 30, 2000 from nine medical institutions of the Kinki Region of Japan. We classified the minimum inhibitory concentration (MIC) of PCG according to the National Committee for Clinical Laboratory Standards (NCCLS) criteria. The overall rate of all types of S. pneumoniae resistance was 53.2% (penicillin-susceptible S. pneumoniae (PSSP): 46.8%, penicillin-intermediate S. pneumoniae (PISP): 42.6%, penicillin-resistant S. pneumoniae (PRSP): 10.6%). In other antimicrobiotics, the resistance (R)/intermediate susceptibility (I) rates (R/I%) were as follows: ceftriaxone, 28.9%; cefotaxime, 7.7%; imipenem, 8.9%; meropenem, 9.8%; clarithromycin, 82.6%; clindamycin, 42.1%; levofloxacin, 0.4%; vancomycin, 0%. We used the polymerase chain reaction to study the mutations of the penicillin-binding proteins pbp1 a, pbp2b, and pbp2x in 140 strains of S. pneumoniae in the MIC for PCG was < 0.5 microgram/ml. Among the 109 strains of PSSP, 32 (29.4%) had no mutation and 77 (70.6%) showed mutation of more than one of the pbp mutations. Among the 31 strains of PISP, only 1 strain (3.2%) was not mutated. Since 70.6% of the strains classified as PSSP had pbp mutations, S. pneumoniae clearly can acquire resistance to anti-microbiotics. In the future, a comprehensive surveillance of S. pneumoniae is necessary.

Serotypes and antimicrobial susceptibility of Streptococcus pneumoniae from clinical specimens

Studies were made on 66 strains of Streptococcus pneumoniae which were obtained from clinical specimens in 1991 through 1993 and showed 19 mm or less of disk inhibition zone diameter (DIZD) against 1 microgram oxacillin (MPIPC) disk. The studies included the determination of their serotypes, antimicrobial susceptibility, and comparison between microbroth dilution (MD) method and Kirby-Bauer (K-B) method. In the study of distribution of serotypes, additional 32 strains which showed 20 mm or more in DIZD were included for study. The results were as follows. 1) About 70% of 98 strains of S. pneumoniae were serotyped by 6 kinds of antisera. Among penicillin-susceptible S. pneumoniae (PSSP), type 3 were 20.6%, type 19, 15.9%, type 6, 14.3%, type 18, 9.5%, type 14, 7.9%, and type 4, 1.6%. Among penicillin-intermediate S. pneumoniae (PISP), and penicillin-resistant S. pneumoniae (PRSP), type 19 were 60%, and type 18, 8.6%. In PISP and PRSP, more than half were type 19, which indicates they are distinctly different from PSSP in serotypical distribution. 2) As to the difference between screening by MPIPC disk and minimum inhibitory concentration (MIC) by benzylpenicillin (PCG), among 66 MPIPC resistant strains, PSSP strains were 31 in number (47%). 3) MIC showed that PISP and PRSP strains were more resistant than PSSP against cefaclor (CCL), cefazolin (CEZ), cefotiam (CTM), cefotaxime (CTX), imipenem (IPM), minocycline (MINO), and erythromycin (EM), but no difference was found in the 2 groups of strains in MIC with clindamycin (CLDM) and ofloxacin (OFLX). 4) All type 3 strains formed mucoid colonies and were resistant to MINO and highly resistant to EM and CLDM. 5) By NCCLS, category of antimicrobial susceptibility is determined against CCL, EM, OFLX, in MD method and K-B method. Against these antibiotics, the complete agreement rates were 75.8%, 92.4% and 86.4% respectively.