Penicillin-resistant Strains Research Articles

Pharmacodynamic target attainment potential of azithromycin, clarithromycin, and telithromycin in serum and epithelial lining fluid of community-acquired pneumonia patients with penicillin-susceptible, intermediate, and resistant Streptococcus pneumoniae

To compare the probability of target attainment (PTA) for macrolides and ketolides against penicillin-susceptible, intermediate, and resistant Streptococcus pneumoniae in both serum and epithelial lining fluid (ELF) of patients with community-acquired pneumonia (CAP). Monte Carlo simulations were used to assess the attainment of the bacterial eradication-linked pharmacodynamic index of the free drug area under the concentration-time curve over 24 hours to minimum inhibitory concentration (fAUC(0-24)/MIC90) by azithromycin, clarithromycin, and telithromycin, at therapeutic doses, against penicillin-susceptible, intermediate, and resistant S. pneumoniae. In serum, azithromycin and clarithromycin were found to have a probability of attaining the recommended fAUC(0-24)/MIC90 ratio of 30 in 50.2% and 74.6%, respectively, of CAP patients with penicillin-intermediate strains, and a probability of 36.9% and 60.7%, respectively, in cases of penicillin-resistant strains. Telithromycin maintained a probability of reaching the fAUC(0-24)/MIC90 ratio of 30 in serum and ELF in 89.1% of CAP patients, regardless of the penicillin resistance of the strain. Clarithromycin results in a higher PTA than azithromycin in the treatment of penicillin-susceptible S. pneumoniae, but both of these agents exhibit a decreasing efficacy as S. pneumoniae penicillin resistance increases. When compared to clarithromycin and azithromycin, telithromycin maintains higher PTA in CAP patients with penicillin-resistant strains of S. pneumoniae.

The incidence of pediatric invasive pneumococcal disease in Chiba prefecture, Japan (2003–2005)

The purpose of the study is to evaluate the incidence, spectrum of clinical manifestations and outcome of invasive pneumococcal disease (IPD) in children in Chiba prefecture, Japan. To determine the precise incidence of IPD in Chiba prefecture, we implemented a retrospective survey of the period from 2003 to 2005. A written questionnaire was sent to 45 hospitals that have pediatric wards, and information was obtained from all hospitals. The questionnaire included the clinical diagnosis, patient's age, underlying disease, prognosis and antimicrobial susceptibility of the isolated strains. During the 3 study years, 130 patients were diagnosed with IPD. The mean annual incidence rates of IPD among children <2 and <5 years were 19.5-23.8 and 12.6-13.8 per 100,000, respectively. Among 130 patients with systemic infection, 66 patients had bacteremia, 39 had pneumonia and 16 had meningitis. Five patients had neurological sequelae and 2 patients died. Seventy-four out of 115 isolates (64.3%) exhibited resistance to penicillin G. The annual incidence of pediatric IPD has remained constant during the study period. Two-third of isolated strains were at least partially resistant to penicillin G. Establishment of appropriate antibiotic therapy against IPD due to penicillin-resistant strains and the introduction of pneumococcal conjugate vaccines are emergent issues in Japan.

Antimicrobial Suseptibility Of &lt;i&gt;Neisserria gonorrhoeae&lt;/i&gt; Isolated From Patients Attending Various Clinics In Pambeguwa, Kaduna State

Antimicrobial resistant strains of gonococcal isolates have spread in many developing countries. In most African countries, the susceptibility of Neisserria gonorrhoeae is rarely tested. The antimicrobial susceptibility of one hundred and eight (108) Neisserria gonorrhoeae was therefore determined. Of the 108 isolates tested, 80 (74.07%) were resistant to penicillin, 74 (68.5%) were resistant to ampicillin. The resistance profiles for the remaining antibiotics tested were as follows: Erythromycin (58.3%), Tetracycline (62%) and gentamicin (25.9%). All the isolates were susceptible to ceftriaxone, cefuroxime and ofloxacin. Of the 80 penicillin resistant strains, 65 (81.3%) were penicillinase producing Neisserria gonorrhoeae (PPNG). The Minimum Inhibitory Concentration (MIC) of Penicillin against 9 gonococcal isolates, Ampicillin against 5 Neisseria gonorrhoeae isolates and Tetracycline against 2 gonococcal isolates was 32.0&#956;g/ml. A total of 108 isolates were susceptible to 0.125&#956;g/ml of ceftriaxone, cefuroxime and ofloxacin respectively. The high prevalence of PPNG and multiple drug resistance strains of Neisseria gonorrhoeae is associated with self-medication and sexual interaction between commercial sex workers (CSWs) resident in Pambeguwa and the long-distance truck drivers. Antimicrobial susceptibility test should be carried out on every gonococcal isolate obtained to ensure effective therapy. The present study was undertaken to assess the antimicrobial susceptibility of gonococcal isolates recovered from patients in Pambeguwa,Kaduna state, Nigeria. Keywords: Neisserria gonorrhoeae, antimicrobial susceptibility, long-distance truck drivers African Journal of Infectious Diseases Vol. 2 (1) 2008: pp. 42-45

In Vitro and In Vivo Activity of Miltefosine Against Penicillin-Sensitive and -Resistant Streptococcus pneumoniae Strains

The in vitro and in vivo activity of miltefosine against penicillin-sensitive and penicillin-resistant pneumococcal strains was studied. The minimum inhibitory concentrations (MICs) of miltefosine were determined in cation-adjusted Mueller Hinton plus 2% lysed horse blood (CAMHB) and in Todd-Hewitt (TH) broth. The respective MICs were higher using CAMHB (128 and 64 mg/L) than using TH broth (4 and 8 mg/L). The In Vivo activity was studied in a murine peritonitis-sepsis model. Miltefosine was orally administered at doses of 15 and 30 mg/kg/day after, at the time of, and before bacterial challenge for 3-5 days. All control and 16 out of the 17 (94.1%) miltefosine-treated animals that were inoculated with the penicillin-sensitive strain died. No survival was observed among control and miltefosine-treated animals inoculated with the penicillin-resistant pneumococcal strain. The In Vivo unresponsiveness of miltefosine in this sepsis model could be attributed to some inhibitory effect of blood, inadequate pharmacokinetics and/or the extracellular localization of the pneumococcus.

Mortality in Penicillin-Resistant Pneumococcal Meningitis

To the Editors: In developing countries, penicillin and chloramphenicol remain widely used to treat meningitis, and few data are available to assess the impact of antibiotic resistance on the outcome of this therapy. In the early 1990s it was shown that mortality and sequelae were increased when children treated with penicillin and chloramphenicol had pneumococcal meningitis caused by intermediately penicillin-resistant strains.1 Poor outcome was consistent with relatively limited penetration of penicillin into the cerebrospinal fluid and lack of inhibition of chloramphenicol on pneumococci at achievable CSF concentrations.1 We have recently analyzed the outcome of children with pneumococcal meningitis treated with penicillin and chloramphenicol (benzylpenicillin 200 000 IU/kg per 24 hours and chloramphenicol 100 mg/kg per 24 hours every 6 hours) in a randomized trial of dexamethazone therapy in Malawi.2 Penicillin and chloramphenicol susceptibility were assessed by disk diffusion. Although the chloramphenicol disk test discriminates between chloramphenicol intermediate and resistant strains, the oxacillin disk can only identify strains as penicillin–nonsusceptible. Nonetheless, it is likely that most strains found to be nonsusceptible in Blantyre by the oxacillin disk test, are intermediately resistant, as in a previous study from Blantyre, all of 8 meningeal, 1 empyema, and 21 carriage isolates nonsusceptible by this disk test were intermediately resistant,3 as were 95% of 146 penicillin–nonsusceptible strains from rural Malawian children.4 Of 229 pneumococcal meningitis isolates available for susceptibility testing, 39 (17%) were nonsusceptible to chloramphenicol (1 intermediate) and 47 nonsusceptible to penicillin (20%).2 In this study, mortality was not influenced by randomization to the dexamethazone group in the children treated with penicillin and chloramphenicol, so the analysis of mortality by resistance is for all the children regardless of their randomization. The risk of death was increased (RR: 1.55; 95% CI: 1.06–2.28; P = 0.03) in children with penicillin nonsusceptible, but chloramphenicol susceptible isolates: 22/45 (48%) versus children infected with fully susceptible strains 45/143 (31%). These data support the previous observation that penicillin plus chloramphenicol fail in the treatment of intermediately penicillin–resistant pneumococcal meningitis.1 Although statistically nonsignificant, there was also an increased death rate 16/35 (46%) associated with chloramphenicol–nonsusceptibility despite penicillin susceptibility (RR: 1.45; 95% CI: 0.94–2.24; P = 0.11). In 2 patients, the strain was nonsusceptible to both drugs; 1 died, and 1 survived with sequelae. Mortality associated with nonsusceptibility to either drug 39/82 (48%) was associated with significantly increased mortality (RR: 1.51; 95% CI: 1.08–2.11; P = 0.016). Survival with sequelae was common in all 3 groups—penicillin and chloramphenicol susceptible (29%), penicillin nonsusceptible only (24%), and chloramphenicol nonsusceptible only (26%). These data suggest that combination therapy (organism susceptible to both drugs) may be superior to monotherapy (resistance to 1 drug) for therapy for pneumococcal meningitis. We caution physicians and pediatricians against the use of penicillin plus chloramphenicol to treat pneumococcal meningitis, as the distribution of inter-mediate penicillin resistance among pneumococci is global. Keith P. Klugman, MBBCh, PhD Medical Research Council University of the Witwatersrand/National Institute for Communicable Diseases Respiratory and Meningeal Pathogens Research Unit Johannesburg, South Africa; and The Rollins School of Public Health Emory University Atlanta, GA Amanda L. Walsh, MSc Amos Phiri, MSc Malawi Liverpool Wellcome Trust Research Laboratories Blantyre, Malawi Elizabeth M. Molyneux, FRCPCH Pediatric Department College of Medicine Blantyre, Malawi

Bacterial resistance surveillance in China: a report from Mohnarin 2004–2005

The aim of this study was to establish a nationwide antimicrobial resistant surveillance network and obtain information on bacterial resistance in China. A total of 4075 clinical bacterial isolates were collected from 17 hospitals in 15 cities throughout China. Antibacterial minimal inhibitory concentrations (MICs) were determined by the standard agar dilution method recommended by Clinical and Laboratory Standards Institute. The results of the MICs revealed the following bacterial resistance characteristics. Oxacillin resistance was shown by 62.9% of Staphylococcus aureus and 82.89% of Staphylococcus epidermidis strains. Penicillin non-sensitivity was show by 40.7% of the Streptococcus pneumoniae strains, which included 10.5% penicillin-resistant strains and 30.2% penicillin-intermediate strains. Five strains of Enterococci were vancomycin-intermediate, but all Enterococci strains were sensitive to teicoplanin. All Staphylococci were susceptible to glycopeptides. A high resistance to macrolides was a predominant characteristic of the Gram-positive cocci. Enterobacteriaceae strains were clearly resistant to the third generation cephalosporins, with the exception of ceftazidime, and the resistance rates ranged from 20 to 70%. About 65% of the Escherichia coli strains were resistant to fluoroquinolones. Carbapenems remained highly active against all the target bacteria. Latamoxef, piperacillin/tazobactam, cefoperazone/sulbactam and cefepime were all active against Enterobacteriaceae, which showed resistant rates of less than 10%. Imipenem resistance was found in 10.6% of Pseudomonas aeruginosa and 10.4% of Acinetobacter baumannii strains, most of which were multidrug resistant isolates. Combinations of beta-lactam/beta-lactamase inhibitor and fluoroquinolones also had potent antibacterial activity against non-fermenters. Amikacin was active against Enterobacteriaceae and P. aeruginosa. In conclusion, methicillin-resistant Staphylococci, penicillin-insensitive S. pneumoniae, macrolides-resistant Gram-positive cocci, cephalosporin-resistant Enterobacteriaceae, multidrug-resistant nonfermenters and fluoroquinolone-resistant E. coli were revealed to be the most serious problems in terms of bacteria resistance in China. No glycopeptides-resistant Staphylococcus strains were isolated, and the appearance of glycopeptides-resistant Enterococci was seldom.

Detection of pbp2b and ermB genes in clinical isolates of Streptococcus pneumoniae

Streptococcus pneumoniae is a major human pathogen. The emergence of penicillin resistant strains since the 1970s has been life threatening and the evolution of the bacteria have enabled itself to develop resistance to many other antibiotics such as the macrolides and the fluoroquinolones. This study aims to characterize S. pneumoniae isolates for the presence of penicillin and macrolide resistance genes. One hundred and twenty clinical isolates of S. pneumoniae were obtained from patients of University Malaya Medical Centre (UMMC). The strains were screened using a multiplex real-time PCR method for the presence of alterations in the genes encoding the penicillin binding proteins: pbp2b, macrolide resistance determinant ermB and the pneumolysin gene, ply. Dual-labelled Taqman probes were used in the real-time detection method comprising three different genes labeled with individual fluorophores at different wavelengths. One hundred and twenty isolates from bacterial cultures and isolates directly from blood cultures samples were analyzed using this assay. A multiplex PCR comprising the antibiotic resistance genes, ermB and and pneumolysin gene (ply), a S. pneumoniae species specific gene, was developed to characterize strains of S. pneumoniae. Out of the 120 pneumococcal isolates, 58 strains were categorized as Penicillin Sensitive Streptococcus pneumoniae (PSSP), 36 as Penicillin Intermediate Streptococcus pneumoniae (PISP) and 26 as Penicillin Resistant Streptococcus pneumoniae (PRSP). All the 58 PSSP strains harboured the pbp2b gene while the 36 PISP and 26 PRSP strains did not harbour this gene, thus suggesting reduced susceptibility to penicillin. Resistance to erythromycin was observed in 47 of the pneumococcal strains while 15 and 58 were intermediate and sensitive to this drug respectively. Susceptibility testing to other beta-lactams (CTX and CRO) also showed reduced susceptibility among the strains within the PISP and PRSP groups but most PSSP strains were sensitive to other antibiotics. The characterization of pneumococcal isolates for penicillin and erythromycin resistance genes could be useful to predict the susceptibility of these isolates to other antibiotics, especially beta-lactams drugs. We have developed an assay with a shorter turnaround time to determine the species and resistance profile of Streptococcus pneumoniae with respect to penicillin and macrolides using the Real Time PCR format with fluorescent labeled Taqman probes, hence facilitating earlier and more definitive antimicrobial therapy which may lead to better patient management.

Increased resistance of Streptococcus pneumoniae isolates to antimicrobial drugs, at a referral hospital in north-west Ethiopia

Beta lactam antibiotics were very effective against Streptococcus pneumoniae. However, resistance to this class of antibiotics has become an increasing problem. Reports of penicillin resistant and multidrug resistant strains are being made in many parts of the world. We examined the drug sensitivity pattern of S. pneumoniae isolates in a retrospective analysis of laboratory records of S. pneumoniae isolates between March 2001 and April 2005 at Gondar University Hospital, Ethiopia. A significant proportion of the isolates were found to be resistant to one or more of the commonly used antibiotics. Furthermore, the isolates appear to be acquiring an increasing resistance to crystalline penicillin, cotrimoxazole and ampicillin. This situation needs immediate attention.

Population Snapshot of EmergentStreptococcus pneumoniaeSerotype 19A in the United States, 2005

Serotype 19A invasive pneumococcal disease (IPD) increased annually in the United States after the introduction of the 7-valent conjugate vaccine (PCV7). To understand this increase, we characterized serotype 19A isolates recovered during 2005. IPD cases during 1998-2005 were identified through population-based surveillance. We performed susceptibility testing and multilocus sequence typing on 528 (95%) of 554 serotype 19A isolates reported in 2005. The incidence of IPD due to serotype 19A increased from 0.8 to 2.5 cases per 100,000 population between 1998 and 2005 (P < .05), whereas the overall incidence of IPD decreased from 24.4 to 13.8 cases per 100,000 population (P < .05). Simultaneously, the incidence of IPD due to penicillin-resistant 19A isolates increased from 6.7% to 35% (P < .0001). Of 151 penicillin-resistant 19A isolates, 111 (73.5%) belonged to the rapidly emerging clonal complex 320, which is related to multidrug-resistant Taiwan(19F)-14. The remaining penicillin-resistant strains were highly related to other clones of PCV7 serotypes or to isolates within major 19A clonal complex 199 (CC199). In 1999, only CC199 and 3 minor clones were apparent among serotype 19A isolates. During 2005, 11 multiple-isolate clonal sets were detected, including capsular switch variants of a serotype 4 clone. PCV7 ineffectiveness against serotype 19A, antibiotic resistance, clonal expansion and emergence, and capsular switching have contributed to the genetic diversity of 19A and to its emergence as the predominant invasive pneumococcal serotype in the United States.

Staphylococcus and the Healing Power of Pus

Staphylococcus aureus infections induce formation of neutrophil-rich abscesses filled with debris from dead phagocytes. Corbin and colleagues report that this pus has antimicrobial powers through the activity of calprotectin. Calprotectin, a member of the S100 family of proinflammatory proteins, acts through chelation of manganese. As manganese is an essential cofactor for several enzymes in S. aureus, this impacts bacterial growth and the bacterium's ability to withstand oxidative stress.

β-Lactam Activity against Penicillin-Resistant Streptococcus pneumoniae Strains Exhibiting Higher Amoxicillin versus Penicillin Minimum Inhibitory Concentration Values: An in vitro Pharmacodynamic Simulation

Background: Activity of simulated serum concentrations after oral therapy with 400 mg cefditoren pivoxil b.i.d., 500 mg cefuroxime axetil b.i.d. and 875/125 mg amoxicillin/clavulanic acid b.i.d. and t.i.d. regimens was explored over 24 h against Streptococcus pneumoniae.Methods: Computerized pharmacodynamic simulations were performed against strains with penicillin/amoxicillin/cefuroxime/cefditoren minimum inhibitory concentrations (MICs, µg/ml) and serotypes: strain 1 (0.25/0.12/1/0.12; serotype 6A), strain 2 (2/4/ 2/0.25; serotype 6B), strain 3 (4/16/4/0.5; serotype 14), and strain 4 (4/16/8/1; serotype 14). Results: Bactericidal activity (≧3 log₁₀ reduction) at 12 and 24 h was obtained against all strains with cefditoren, against strains 1 and 2 with cefuroxime and amoxicillin/clavulanic acid t.i.d., but only against strain 1 with amoxicillin/clavulanic acid b.i.d.. Bactericidal activity at 24 h was related to T > MIC of >30% dosing interval, 1.7–2.0 log₁₀ reductions with T > MIC of 20–30%, and <1 log₁₀ reduction or regrowth with T > MIC of 0%. Conclusions: It is difficult to achieve pharmacodynamic coverage and bactericidal activity by physiological concentrations of oral β-lactams against penicillin-resistant pneumococcal strains exhibiting higher amoxicillin versus penicillin MICs. Cefditoren may offer alternatives.

Changes in Serotypes and Antimicrobial Susceptibility of Invasive Streptococcus pneumoniae Strains in Cleveland: a Quarter Century of Experience

The serotypes and susceptibilities to penicillin, macrolides, and clindamycin of 1,655 invasive isolates of Streptococcus pneumoniae recovered between 1979 and 2004 were determined. A precipitous decrease of 61% in the number of isolates was found following 2000, the year of 7-valent protein-conjugated pneumococcal vaccine (PCV7) introduction (139 versus 55 per 2-year period prior to versus after 2000; P < 0.001). This decrease was 84% in children <5 years old (80 versus 13 per 2-year period; P < 0.001) and 18 to 23% in other age groups (P, not significant). PCV7 serotypes decreased by 76% overall (103 versus 25 per 2-year period; P < 0.001) and by 92% in children <5 years old (65 versus 5 per 2-year period; P < 0.001), with significant decreases in six of the seven PCV serotypes. Other serotypes, except for type 19A, decreased from 32 to 22 per 2-year period, while type 19A increased from 4 to 8 per 2-year period, although none of these changes reached significance. Drug resistance emerged slowly, with the first penicillin-intermediate strain isolated in 1980 and the first macrolide/lincosamide-resistant strain isolated in 1984. The first penicillin-resistant strain was isolated in 1993. Resistance increased steadily thereafter until 2003-2004, when 51.1% of isolates were penicillin nonsusceptible and 53.3% were macrolide resistant. Clindamycin resistance remained low until 2003-2004, when 26.7% of strains were resistant; this was associated with the emergence of multidrug-resistant type 19A strains. This study documents the emergence of resistance over a quarter century among invasive pneumococci in the Cleveland area, as well as the reduction in disease caused by PCV7 serotypes following the introduction of PCV7 in 2000.

Implications of Streptococcus pneumoniae penicillin resistance and serotype distribution in Kuwait for disease treatment and prevention.

Streptococcus pneumoniae causes serious infections. Treatment is difficult because of the emergence of penicillin resistance in S. pneumoniae. Pneumococcal vaccines offer the promise of control and prevention of pneumococcal infections. Serotype prevalence and penicillin susceptibility data for a country will predict the usefulness of the vaccines in that country. In Kuwait, the 23-valent polysaccharide and the 7-valent conjugate vaccines are being used without knowledge of the prevalent serotypes in the country. To obtain the necessary background information, data on penicillin susceptibility and serogroups were obtained from 397 consecutive clinical isolates collected during 2004 and 2005. Two hundred fifty-three isolates (64%) were penicillin resistant, and resistance was significantly higher in patients < or =15 years old and among the upper respiratory tract and eye isolates. The most common serotypes were 23F, 19F, 6A, 6B, 14, and 19A. Among the penicillin-resistant strains, the most common serotypes were 23F, 19F, 6B, 14, and 9A. Among the invasive strains, the most common serotypes were 14, 23F, 19A, and 9V. The polysaccharide vaccine gave 82% coverage against invasive infections in all age groups >2 years. The coverage of the 7-valent conjugate vaccine against invasive serotypes in children < or =2 years old was 55%. This moderate coverage by the conjugate vaccine against invasive infections in children necessitates a revised strategy on the use of the present conjugate vaccine and shows the need for formulation of an improved vaccine for superior coverage for Kuwait and possibly other countries of the Arabian Gulf.

Influence of penicillin/amoxicillin non-susceptibility on the activity of third-generation cephalosporins against Streptococcus pneumoniae

To study the influence of penicillin/amoxicillin non-susceptibility on the activity of third-generation cephalosporins, 430 consecutive penicillin non-susceptible Streptococcus pneumoniae 2007 isolates received in the Spanish Reference Pneumococcal Laboratory were tested. For comparative purposes, 625 penicillin-susceptible 2007 isolates were also tested. Susceptibility was determined by agar dilution using Mueller-Hinton agar supplemented with 5% sheep blood. Penicillin-susceptible strains were susceptible to amoxicillin, cefotaxime and ceftriaxone, 99.8% to cefpodoxime and 99.5% to cefdinir, and were inhibited by 0.12 microg/ml of cefditoren and 4 microg/ml of cefixime. Penicillin-intermediate strains were susceptible to cefotaxime and ceftriaxone, with <50% susceptibility to cefdinir and cefpodoxime. The MIC(50) and MIC(90) values of cefditoren were 0.25 microg/ml and 0.5 microg/ml, respectively, whereas cefixime exhibited only marginal activity (MIC(90)=16 microg/ml). Penicillin-resistant strains were resistant to cefdinir and cefpodoxime, with 74.8% and 94.1% susceptibility to cefotaxime and ceftriaxone, respectively. Cefditoren MIC(50)/MIC(90) (0.5/1 microg/ml) were lower than cefotaxime and ceftriaxone. Among amoxicillin non-susceptible strains, susceptibility to cefdinir and cefpodoxime was <10%, and susceptibility to cefotaxime decreased from 87.9% in the intermediate category to 63.0% in the resistant group. Cefditoren MIC(50)/MIC(90) (0.5/1 microg/ml) were lower than cefotaxime. In conclusion, the activity of cefixime, cefdinir and cefpodoxime was highly affected by penicillin/amoxicillin non-susceptibility, while parenteral third-generation cephalosporins exhibited higher intrinsic activity (MIC(90)=1 microg/ml for penicillin-resistant and 2 microg/ml for amoxicillin-resistant strains). Cefditoren exhibited one-dilution lower MIC(90) values for these strains, even against those of the most troublesome serotypes.

Antimicrobial susceptibility of neisseria gonorrhoeae isolated from patients attending private clinics in Zaria

A total of 125 Neisseria gonorrhoeae strains were isolated from patients attending private clinics in Zaria, Kaduna State, Nigeria. Out of the 125 gonococcal isolates, 90 (72%) were resistant to penicillin G, 85 (68%) to ampicillin, 70 (56%) to tetracycline, 55 (44%) to erythromycin and 26 (22%) isolates were resistant to gentamicin. All the 125 Neisseria gonorrhoeae isolates were susceptible to ceftriaxone, cefuroxime and ofloxacin. Out of the 90 Neisseria gonorrhoeae isolates resistant to penicillin, 65 (72.2%) were positive for β-lactamase production (PPNG). The remaining 25 (27.7%) penicillin resistant strains were β-lactamase negative. The findings of this study have shown high prevalence of multi-drug resistant strains of Neisseria gonorrhoeae amongst attendees of private clinics in Zaria. African Journal of Clinical Experimental Microbiology Vol. 8 (2) 2007: pp. 101-106

Heteroresistance to penicillin in Streptococcus pneumoniae

Heteroresistance to beta-lactam antibiotics has been mainly described for staphylococci, for which it complicates diagnostic procedures and therapeutic success. This study investigated whether heteroresistance to penicillin exists in Streptococcus pneumoniae. Population analysis profile (PAP) showed the presence of subpopulations with higher penicillin resistance in four of nine clinical pneumococcal strains obtained from a local surveillance program (representing the multiresistant clones ST179, ST276, and ST344) and in seven of 16 reference strains (representing the international clones Spain(23F)-1, Spain(9V)-3, Spain(14)-5, Hungary(19A)-6, South Africa(19A)-13, Taiwan(23F)-15, and Finland(6B)-12). Heteroresistant strains had penicillin minimal inhibitory concentrations (MICs) (for the majority of cells) in the intermediate- to high-level range (0.19-2.0 mug/ml). PAP curves suggested the presence of subpopulations also for the highly penicillin-resistant strains Taiwan(19F)-14, Poland(23F)-16, CSR(19A)-11, and CSR(14)-10. PAP of bacterial subpopulations with higher penicillin resistance showed a shift toward higher penicillin-resistance levels, which reverted upon multiple passages on antibiotic-free media. Convergence to a homotypic resistance phenotype did not occur. Comparison of two strains of clone ST179 showed a correlation between the heteroresistant phenotype and a higher-penicillin MIC and a greater number of altered penicillin-binding proteins (PBP1a, -2b, and -2x), respectively. Therefore, heteroresistance to penicillin occurs in international multiresistant clones of S. pneumoniae. Pneumococci may use heteroresistance to penicillin as a tool during their evolution to high penicillin resistance, because it gives the bacteria an opportunity to explore growth in the presence of antibiotics before acquisition of resistance genes.

Utilization of lactoferrin to fight antibiotic-resistant mammary gland pathogens1,2

The widespread use of antibiotics has lead to the increased presence of pathogens that are less susceptible to their antibacterial effect. Lactoferrin (Lf) is naturally produced by the mammary gland. Lactoferrin is the main whey protein in human milk and is also present in cow's milk but at a much lower concentration than in human milk. This protein appears to have many biological functions, including antibacterial and antiinflammatory activities. The best-known effect of Lf is to bind iron that is essential for bacterial growth. However, the cationic nature of this protein also appears to be important for the antimicrobial activity of this protein. Lactoferrin has a weak antibacterial effect when used alone, but interestingly, Lf appears much more effective when used at low concentration in combination with several antibiotics. The most striking observation is that Lf increases the inhibitory activity of penicillin up to 4-fold in most penicillin-susceptible Staphylococcus aureus strains, whereas this increase was 4- to 16-fold in penicillin-resistant strains. Indeed, Lf reduces beta-lactamase activity in S. aureus strains producing this enzyme. Transcription of beta-lactamase gene is dramatically repressed in the presence of Lf. We evaluated the efficacy of intramammary treatments containing penicillin G or bovine Lf (bLf), or both, to cure chronic mastitis caused by a clinical isolate of S. aureus highly resistant to beta-lactam antibiotics. In a first trial, mastitis was induced in lactating cows by injecting a low dose of S. aureus through the teat canal of all quarters. Bacterial cure rate was null for control quarters, 11.1% for bLf, 9.1% for penicillin, and 45.5% for the combination of bLf and penicillin. A second trial was undertaken to investigate the effect of an extended therapy on chronic mastitis acquired in a previous lactation. Quarters were treated with 100,000 IU of penicillin G with or without 250 mg of bLf for 7 d. Bacterial cure rate was greater for the bLf + penicillin combination (33.3%) compared with penicillin alone (12.5%). In conclusion, bLf added to penicillin is an effective combination for the treatment of stable S. aureus infections resistant to beta-lactam antibiotics.

Penicillin Resistance Not a Factor in Outcome from Invasive Streptococcus pneumoniae Community-Acquired Pneumonia in Adults When Appropriate Empiric Therapy Is Started

Invasive Streptococcus pneumoniae pneumonia among adults due to penicillin-resistant or intermediate resistant strains was investigated to determine whether these patients responded poorly to common antibiotic regimens compared to pneumonia due to susceptible strains. During a 21-year period (1983-2003), clinical outcome was analyzed among 3 groups of adults, 19 with resistant, 33 with intermediate, and 133 with susceptible invasive S pneumoniae pneumonia admitted to hospitals in Huntington, West Virginia. Adults with resistant and intermediate infections were matched by age and month of admission to a group of 133 adults with penicillin-susceptible infections. All isolates of resistant and intermediate infections were capsular serotypes/serogroups 6, 9, 14, 19, and 23, and isolates of susceptible infections included 24 different serotypes/serogroups. Case fatality rates were calculated for deaths that occurred during the first 7, first 14, and first 21 days of hospitalization. Minimal inhibitory concentration (MIC) was determined by E-test and capsular serotype by Quellung procedures. The resistant and susceptible groups did not differ in several measures of severity of illness, including admission vital signs, duration of fever, mean total leukocyte count, number of lobes involved, preexisting underlying diseases, and antibiotic treatment regimens. There were no significant differences in case fatality rates between the 3 groups of pneumonia by days in hospital, age, severity of illness, and empiric antibiotic treatment regimen with a cephalosporin and a macrolide, the most common antibiotic regimen. These findings provide evidence that combination antibiotic regimens effective in the treatment of invasive susceptible S pneumoniae pneumonia are equally effective in the treatment of invasive resistant (MIC = 2-4 microg/mL) and of intermediate (MIC = 0.1-1 microg/mL) S pneumoniae pneumonia.

Streptococcus pneumoniae: estudo das cepas isoladas de liquor

OBJETIVO: Determinar a freqüência dos sorotipos capsulares e a susceptibilidade antimicrobiana de cepas de Streptococcus pneumoniae, assim como dar suporte à indicação de vacinas disponíveis e ao uso de antimicrobianos. MÉTODOS: Neste estudo retrospectivo, foram adotadas metodologias padronizadas para identificar, sorotipar e determinar a susceptibilidade à penicilina, cefotaxima e vancomicina. O estudo foi realizado com cepas de pneumococo isoladas de liquor em pacientes atendidos nos hospitais públicos e em três hospitais particulares do Distrito Federal no período de janeiro de 1995 a dezembro de 2004. A identificação e a determinação de susceptibilidade a antimicrobianos foi realizada no Laboratório Central de Saúde Pública no Distrito Federal. A sorotipagem foi realizada no Instituto Adolfo Lutz. RESULTADOS: Foram isoladas 232 cepas de pneumococo, compreendendo 126 cepas (54,31%) de pacientes do sexo masculino. A idade dos pacientes variou de 0 a 62 anos, sendo agrupados em faixas etárias de 0 a 5, 6 a 17, 18 a 50 e acima de 50 anos. Identificaram-se 36 sorotipos distintos. Desses destacaram-se oito: 14, 6B, 18C, 5, 19F, 23F, 9V e 6A. O teste de oxacilina caracterizou 67 cepas resistentes à penicilina; dessas, 47 foram confirmadas pelo E teste com resistência de nível intermediário. Nenhuma cepa apresentou resistência de alto nível. CONCLUSÃO: A resistência do pneumococo à penicilina apresentou um aumento gradativo nos últimos 10 anos no Distrito Federal. Os sorotipos mais isolados na faixa etária de 0 a 5 anos foram também os mais envolvidos na resistência à penicilina, e estão incluídos na vacina 7-valente.

&amp;lt;i&amp;gt;Streptococcus pneumoniae:&amp;lt;/i&amp;gt; a study of strains isolated from cerebrospinal fluid

To determine the frequency of capsular serotypes and the antimicrobial susceptibility of strains of Streptococcus pneumoniae, as well as to provide recommendations on the use of available vaccines and antimicrobial drugs. In this retrospective study, standard procedures were followed to identify, serotype, and determine bacterial susceptibility to penicillin, cefotaxime, and vancomycin. Pneumococcal strains were isolated from the cerebrospinal fluid (CSF) of patients admitted to nine public and three private hospitals in Distrito Federal, Brazil, between January 1995 and December 2004. Identification and antimicrobial susceptibility tests were carried out at the Central Laboratory of Public Health (Laboratório Central de Saúde Pública). Serotyping was performed at Instituto Adolfo Lutz. A total of 232 pneumococcal strains were isolated, including 126 (54.31%) strains from male patients. Patients had an age range of 0 to 62 years and were distributed into four age groups: 0 to 5, 6 to 17, 18 to 50, and above 50. From the 36 distinct serotypes identified, eight were more prevalent: 14, 6B, 18C, 5, 19F, 23F, 9V, and 6A. The oxacillin test identified 67 penicillin-resistant strains, out of which 47 were confirmed by the E test as having intermediate level of resistance. None of the strains exhibited high-level resistance. Pneumococcal resistance to penicillin has gradually increased over the last 10 years in Distrito Federal. Serotypes more frequently isolated in the 0 to 5 years age group were the same involved in penicillin-resistance, all of which are covered by the 7-valent vaccine.