High-level Penicillin Resistance Research Articles

Updated guideline for the management of upper respiratory tract infections in South Africa: 2008

Introduction: Inappropriate use of antibiotics for non-severe upper respiratory tract infections (URTIs), many of which are viral, adds to the burden of antibiotic resistance. Antibiotic resistance is increasing in Streptococcus pneumoniae, the microorganism responsible for most cases of acute otitis media (AOM) and acute bacterial sinusitis (ABS). Method: The Infectious Diseases Society of Southern Africa held a multidisciplinary meeting to draw up a national guideline for the management of URTIs in 2003. Background information reviewed included randomised controlled trials, existing URTI guidelines and local antibiotic susceptibility patterns. The initial document was drafted at the meeting. Subsequent drafts were circulated to members of the working group for modification. The guideline was published in the South African Medical Journal in 2004 and was a consensus document based upon the opinions of the working group. In 2008 it was decided to update and republish the guideline. This was done electronically using the same working group members, including overseas experts. Output: Penicillin remains the drug of choice for tonsillopharyngitis. Single-dose parenteral administration of benzathine penicillin is effective, but many favour oral administration twice daily for 10 days. Amoxycillin remains the drug of choice for both AOM and ABS. A dose of 90 mg/kg/day is recommended in general, which should be effective for pneumococci with high-level penicillin resistance (this is particularly likely in children ≤2 years of age, in day-care attendees, in cases with prior AOM within the past six months, and in children who have received antibiotics within the last three months). Alternative antibiotic choices are given in the guideline with recommendations for their specific indications. These antibiotics include amoxycillin-clavulanate, some cephalosporins, the macrolide/azalide and ketolide groups of agents and the respiratory fluoroquinolones. Conclusion: The guideline should assist rational antibiotic prescribing for URTIs. However, it should be continuously updated when new information becomes available from randomised controlled trials and surveillance studies of local antibiotic susceptibility patterns.

Synergistic effect between dieckol from Ecklonia stolonifera and β-lactams against methicillin-resistant Staphylococcus aureus

We have been attempting for some time to discover a compound evidencing antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). The dieckol isolated from Ecklonia stolonifera has been shown to exhibit antibacterial activity against methicillin-susceptible S. aureus (MSSA) and MRSA. The minimum inhibitory concentrations (MICs) of dieckol were determined in a range of 32 to 64 μg/mL against standard MSSA and MRSA strains. Furthermore, dieckol clearly reversed the high-level ampicillin and penicillin resistance of MRSA. The MICs of ampicillin against two standard strains of MRSA were dramatically reduced from 512 to 0.5 μg/mL in combination with 1/4 MIC of dieckol (16 μg/mL). The fractional inhibitory concentration (FIC) indices of ampicillin and penicillin were measured from 0.066 to 0.266 in combination with 8 or 16 μg/mL of dieckol against all tested MRSA strains, thereby suggesting that dieckol-ampicillin or dieckol-penicillin combinations exert a synergistic effect against MRSA. The results of this study indicate that dieckol, administered in combination with β-lactams, may prove effective in the treatment of MRSA infections. Our finding may also contribute to the development of an alternative phytotherapeutic anti-MRSA agent.

Characterization of tRNA-dependent Peptide Bond Formation by MurM in the Synthesis of Streptococcus pneumoniae Peptidoglycan

MurM is an aminoacyl ligase that adds l-serine or l-alanine as the first amino acid of a dipeptide branch to the stem peptide lysine of the pneumococcal peptidoglycan. MurM activity is essential for clinical pneumococcal penicillin resistance. Analysis of peptidoglycan from the highly penicillin-resistant Streptococcus pneumoniae strain 159 revealed that in vivo and in vitro, in the presence of the appropriate acyl-tRNA, MurM(159) alanylated the peptidoglycan epsilon-amino group of the stem peptide lysine in preference to its serylation. However, in contrast, identical analyses of the penicillin-susceptible strain Pn16 revealed that MurM(Pn16) activity supported serylation more than alanylation both in vivo and in vitro. Interestingly, both MurM(Pn16) acylation activities were far lower than the alanylation activity of MurM(159). The resulting differing stem peptide structures of 159 and Pn16 were caused by the profoundly greater catalytic efficiency of MurM(159) compared with MurM(Pn16) bought about by sequence variation between these enzymes and, to a lesser extent, differences in the in vivo tRNA(Ala):tRNA(Ser) ratio in 159 and Pn16. Kinetic analysis revealed that MurM(159) acted during the lipid-linked stages of peptidoglycan synthesis, that the d-alanyl-d-alanine of the stem peptide and the lipid II N-acetylglucosaminyl group were not essential for substrate recognition, that epsilon-carboxylation of the lysine of the stem peptide was not tolerated, and that lipid II-alanine was a substrate, suggesting an evolutionary link to staphylococcal homologues of MurM such as FemA. Kinetic analysis also revealed that MurM recognized the acceptor stem and/or the TPsiC loop stem of the tRNA(Ala). It is anticipated that definition of the minimal structural features of MurM substrates will allow development of novel resistance inhibitors that will restore the efficacy of beta-lactams for treatment of pneumococcal infection.

Pneumococcal antimicrobial resistance: therapeutic strategy and management in community-acquired pneumonia

Streptococcus pneumoniae has been consistently shown to represent the most frequent causative agent of community-acquired pneumonia (CAP) and pneumococcal antibiotic resistance towards different families of antibiotics continues to be a much-debated issue. Microbial resistance causes a great deal of confusion in choosing an empirical treatment for pneumonia and this makes it necessary to know which factors actually determine the real impact of antimicrobial resistance on the outcome of pneumococcal infections. Several different aspects have to be taken into account when analyzing this matter, such as the study design, the condition of the patient at the time of diagnosis, the choice of the initial antimicrobial regimen (combination or monotherapy) and the pharmacokinetic/pharmacodynamic variables of the chosen antibiotic. It is generally accepted that in the treatment of β-lactam-resistant pneumococcal infections, the use of standard antipneumococcal β-lactam agents is unlikely to impact negatively on the outcome of CAP when appropriate agents are given in sufficient doses. As a general rule, for infections with penicillin-sensitive strains, penicillin or an aminopenicillin in a standard dosage will be effective; in the cases of strains with intermediate resistance, β-lactam agents are still considered appropriate treatment although higher dosages are recommended; finally, infections with isolates of high-level penicillin resistance should be treated with alternative agents such as the third-generation cephalosporins or the new antipneumococcal fluoroquinolones. In areas of high prevalence of high-level macrolide resistance, empirical monotherapy with a macrolide is not optimal for the treatment of hospitalised patients with moderate or moderately-severe CAP. Fluoroquinolones are considered to be excellent antibiotics in the treatment of pneumococcal CAP in adults, but their general recommendation has been withheld due to fears of a widespread development of resistance. Most international guidelines recommend combination therapy (β-lactam plus a macrolide) for the treatment of hospitalised patients with CAP.

Updated guideline for the management of upper respiratory tract infections in South Africa: 2008

Introduction: Inappropriate use of antibiotics for non-severe upper respiratory tract infections (URTIs), many of which are viral, adds to the burden of antibiotic resistance. Antibiotic resistance is increasing in Streptococcus pneumoniae, the microorganism responsible for most cases of acute otitis media (AOM) and acute bacterial sinusitis (ABS). Method: The Infectious Diseases Society of Southern Africa held a multidisciplinary meeting to draw up a national guideline for the management of URTIs in 2003. Background information reviewed included randomised controlled trials, existing URTI guidelines and local antibiotic susceptibility patterns. The initial document was drafted at the meeting. Subsequent drafts were circulated to members of the working group for modification. The guideline was published in the South African Medical Journal in 2004 and was a consensus document based upon the opinions of the working group. In 2008 it was decided to update and republish the guideline. This was done electronically using the same working group members, including overseas experts. Output: Penicillin remains the drug of choice for tonsillopharyngitis. Single-dose parenteral administration of benzathine penicillin is effective, but many favour oral administration twice daily for 10 days. Amoxycillin remains the drug of choice for both AOM and ABS. A dose of 90 mg/kg/day is recommended in general, which should be effective for pneumococci with high-level penicillin resistance (this is particularly likely in children ≤2 years of age, in day-care attendees, in cases with prior AOM within the past six months, and in children who have received antibiotics within the last three months). Alternative antibiotic choices are given in the guideline with recommendations for their specific indications. These antibiotics include amoxycillin-clavulanate, some cephalosporins, the macrolide/azalide and ketolide groups of agents and the respiratory fluoroquinolones. Conclusion: The guideline should assist rational antibiotic prescribing for URTIs. However, it should be continuously updated when new information becomes available from randomised controlled trials and surveillance studies of local antibiotic susceptibility patterns.

Adenosine phosphonate inhibitors of lipid II: Alanyl tRNA ligase MurM from Streptococcus pneumoniae

Adenosine and 2′-deoxyadenosine phosphonate transition state analogues act as the first inhibitors for the MurMN/FemABX family of tRNA-dependent ligases implicated in high-level penicillin resistance in Gram-positive bacteria.

Nasopharyngeal colonization and penicillin resistance among pneumococcal strains: a Worldwide 2004 update

Surveillance of nasopharyngeal pneumococcus has proven to be a valuable tool for the monitoring of antibiotic resistance. We reviewed the latest information on colonization rate and penicillin resistance by making a MEDLINE search, using the terms "nasopharyngeal carriage" and "Streptococcus pneumoniae". Out of 225 articles found, data from 109 recent publications (89% from 1996-2003) were analyzed. Data were reported from 41 countries of six continents. Individuals under the age of five (64.3%) or 10 years (85.7%) were enrolled, including children attending day-care centers (32.1%) or orphanages (3.6%), and healthy individuals (78.6%) or sick patients (43.6%); biological samples were collected mainly by nasopharyngeal swabs (89.3%). The highest colonization rates were reported from Africa (85-87.2%), where several authors did not find high rates of penicillin resistance. On the other hand, studies conducted in North and Central America reported high-level penicillin resistance at rates of approximately 20-30%. Great variation in the rates of pneumococcal colonization and penicillin resistance were observed within regions or continents. There were also considerable differences in similar populations located in different areas of the same country. Data regarding pneumococcal colonization and penicillin resistance are not available from most countries. We also examined the use of antibiotics to treat pneumococcal infections.

Antimicrobial resistance patterns and serotype distribution of invasive Streptococcus pneumoniae isolates from children in Taiwan from 1999 to 2004

Streptococcus pneumoniae causes substantial morbidity and mortality worldwide. Because only limited data are available for the antibiotic resistance patterns and seroepidemiology of invasive S. pneumoniae isolates in Taiwanese children, this national surveillance of invasive pneumococcal infections in children was conducted during a 5-year period. Invasive isolates of S. pneumoniae were obtained from sterile sites (yielding blood and cerebrospinal, pleural, and intra-articular fluids) in children (aged ≤14 years) at a total of 40 regional hospitals and medical centers distributed throughout Taiwan. The collection period was between July 1999 and June 2004, with a total of 286 isolates (including 30 cerebrospinal fluids) collected. All the samples were sent to the Center for Disease Control in Taipei for serotyping and susceptibility testing. Of the 286 S. pneumoniae isolates studied, the 5 most common serotypes were 14 (28.3%), 23F (21.0%), 6B (17.1%), 19F (13.6%), and 3 (4.9%). Intermediate- and high-level penicillin resistance was determined for 50.7% and 25.5% of the isolates, respectively. Isolate resistance was demonstrated to erythromycin (93%), tetracycline (82.2%), trimethoprim/sulfamethoxazole (79.4%), cefotaxime (11.2%), and levofloxacin (0.3%). Multiple drug resistance was found for each serotype, but mostly in types 14, 23F, 6B, and 19F. Overall, 85.0% of the serotypes, 90.8% of the penicillin-nonsusceptible S. pneumoniae (PNSSP), and 90.1% of the multiple drug-resistant (MDR) isolates were covered by the heptavalent pneumococcal conjugated vaccine (PCV7). In this study, we found a diverse pulse-field gel electrophoresis pattern among MDR isolates: a high prevalence of drug resistance and a continued increasing trend in penicillin resistance among nationwide pneumococcal isolates from children in Taiwan. The highest prevalence of invasive pneumococcal disease was in children aged 2 to 5 years, and the highest PNSSP prevalence and highest PCV7 coverage were in children aged <2 years. In terms of reducing the risk of invasive pneumococcal illness in Taiwan, the use of PCV7 is likely to have a beneficial effect similar to that obtained in countries that have used it.

Effect of Penicillin Resistance on Presentation and Outcome of Nonenterococcal Streptococcal Infective Endocarditis

Background and Aims: Most cases of infective endocarditis are caused by nonenterococcal streptococci. The emergence of strains resistant to penicillin is increasingly recognized worldwide. This study sought to assess the effect of penicillin resistance on presentation and outcome of streptococcal endocarditis. Methods: A retrospective study was conducted in a single tertiary care hospital. Results: Between August 1996 and December 2004, patients infected with nonenterococcal streptococcal endocarditis and known minimal inhibitory concentrations (MICs) to penicillin were included in this study. A total of 62 cases were identified: 48 (77%) cases of the streptococcal endocarditis were caused by viridans streptococci. The most common species groups identified were Streptococcus mitis in 12 (19%) cases, Streptococcus oralis in 9 (15%) cases, Streptococcus sanguis in 7 (11%) cases and Streptococcus mutans in 7 (11%) cases. There were 36 male and 26 female patients with a median age of 46 years (range: 1–85). Twenty-two patients (35%) had peripheral embolization and 10 patients (16%) died in hospital. Twenty-eight (45%) of the 62 patients were infected with streptococcal strains of MICs ≧0.125 µg/ml to penicillin. Infection with streptococcal strains of MICs ≧0.125 µg/ml to penicillin was associated with a lower incidence of all-site embolization, but was not associated with higher mortality or increased frequency of surgery. Conclusions: High-level penicillin resistance of the streptococci responsible for endocarditis was increasingly common and medical therapy with vancomycin had a good response. Penicillin resistance was associated with a decreased risk of embolization, but was not associated with higher mortality.

Combinations of PBPs and MurM protein variants in early and contemporary high-level penicillin-resistant Streptococcus pneumoniae isolates in Spain

High-level penicillin resistance in Streptococcus pneumoniae requires extensive re-modulation of the penicillin-binding proteins (PBPs), and murM gene function is also required for the expression of resistance. In this work, we determined whether specific changes in PBPs were associated with specific MurM variants. Two collections of highly penicillin-resistant (MIC 2-8 mg/L) isolates, including 10 early (1997-1998) and 23 contemporary (2002-2004) isolates, were studied. Most of the isolates belonged to clones Spain(6B)-2 (13 strains), Spain(23F)-1 (10 isolates) and Spain(14)-5 (20 isolates). Different protein variants of MurM (MA, MB5, MB6, MB9 and MB10), PBP1A (A-C), PBP2B (A-D) and PBP2X (A-C) were recognized, including two murM alleles not previously described. Particular [MurM-PBP1A-2B-2X] allelic combinations were predominant among the different clones, including [MA-B-B-B] for old (MIC 2 mg/L) and [MB10-C-A-B] for recent (MIC 4-8 mg/L) Spain(6B)-2 isolates, [MA-A-C-A] for Spain(23F)-1 and [MB5-A-A-A] in Spain(14)-5 isolates. Although S. pneumoniae has a basic recombinational population structure, our results indicate remarkable conservation of PBPs and MurM protein types within each clone. This suggests that particular PBPs-MurM combinations tend to be preserved and may have an independent evolutionary history in particular clones.

Analysis of mutations in the pbp genes of penicillin-non-susceptible pneumococci from Turkey

Sequence analysis of the pbp genes from 20 Streptococcus pneumoniae isolates from Turkey (eight with high-level penicillin-resistance, nine with low-level penicillin-resistance, and three that were penicillin-susceptible) was performed and phylogenetic trees were constructed. Most isolates clustered together within a single branch that was distinct from sequences deposited previously in GenBank, which suggests that these isolates have probably evolved following new recombination events. The most prominent active-site mutations, which have also been associated previously with resistance, were T371A in PBP1a, E481G followed by T451A in PBP2b, and T338A in PBP2x. All isolates also possessed a (570)SVES/TK(574) block in the PBP2b sequence, instead of the QLQPT sequence of R6, which is fairly uncommon in GenBank sequences. This is the first study to analyse alterations in the pbp sequences of pneumococci isolated in Turkey.

High carriage rate of high-level penicillin-resistant Streptococcus pneumoniaein a Taiwan kindergarten associated with a case of pneumococcal meningitis

BackgroundThe Taiwan19F-14 Streptococcus pneumoniae clone and its variants are being found with increasing frequency in the Asia-Pacific region. A 5-year old child with S. pneumoniae meningitis caused by a high-level penicillin resistant strain (MIC = 4 μg/ml) was admitted to a hospital in southern Taiwan. We carried out a study to determine the potential source of this strain.MethodsNasopharyngeal cultures were obtained from all children attending the same kindergarten as the index case. To determine their relatedness all isolates were compared by serotype, antimicrobial susceptibility profile and pulsed field gel electrophoresis (PFGE).ResultsA high proportion of the children including the index case (32/78, 41.0%) carried S. pneumoniae in their nasopharynx (NP). The most common serotype was 19F (13/32, 40.6%). The PFGE types of the 19F serotype isolates obtained from the patient's blood, CSF and NP were identical and were related to 11 other serotype 19F NP isolates including 10 that were indistinguishable from the Taiwan19F-14 clone. All 14 isolates had similar high-level penicillin and multi-drug resistance. The serotypes of the other 19 NP isolates included 6A (2), 6B (10), 23F (5), 9V (1) and 3 (1). The overall rate of penicillin resistance in these S. pneumoniae from these children was 87.5% (28/32), with an MIC50 of 2 and MIC90 of 4 ug/ml. In addition, multi-drug resistant-isolates (isolates resistant to 3 different classes of antimicrobials) accounted for 87.5% (28/32) of all isolates.ConclusionThe high carriage rate of high-level penicillin- and multi-drug- resistant S. pneumoniae in a kindergarten associated with a case of pneumococcal meningitis emphasizes the need for restraint in antibiotic use and consideration of childhood immunization with conjugate pneumococcal vaccine to prevent the further spread of resistant S. pneumoniae in Taiwan.

Impact of the European Antimicrobial Resistance Surveillance System on the development of a national programme to monitor resistance in Staphylococcus aureus and Streptococcus pneumoniae in Ireland, 1999–2003

Presented here is the 5-year impact of a national antimicrobial resistance surveillance system in Ireland, which was introduced in accordance with the European Antimicrobial Resistance Surveillance System (EARSS). Participation in EARSS began in Ireland in 1999. Initially, 12 laboratories serving a mix of general and tertiary hospitals participated, but by 2003, participation had increased to 28 laboratories with a population coverage of 89%. During 1999-2003, 4,146 episodes of Staphylococcus aureus bacteraemia were reported, and methicillin resistance was detected in 1,709 (41.2%) of these isolates. Over the same period, 1,245 invasive (blood or cerebrospinal fluid) episodes of Streptococcus pneumoniae infection were reported, and 160 (12.9%) isolates were found to be non-susceptible to penicillin, with 23 (1.8%) demonstrating high-level penicillin resistance. By 2003, most Irish hospitals were participating in EARSS, which has been a catalyst for the development of a national antimicrobial resistance surveillance programme.

Guidelines for the Management of Upper Respiratory Tract Infections

Introduction: Inappropriate use of antibiotics for upper respiratory tract infections (URTIs), many of which are viral, adds to the burden of antibiotic resistance. Antibiotic resistance is increasing in Streptococcus pneumoniae, responsible for most cases of acute otitis media (AOM) and acute bacterial sinusitis (ABS).Method: The Infectious Diseases Society of Southern Africa held a multidisciplinary meeting to draw up a national guideline for the management of URTIs. Background information reviewed included randomised controlled trials, existing URTI guidelines and local antibiotic susceptibility patterns. The initial document was drafted at the meeting. Subsequent drafts were circulated to members of the working group for modification. The guideline is a consensus document based upon the opinions of the working group.Output: Penicillin remains the drug of choice for tonsillopharyngitis. Single-dose parenteral administration of benzathine penicillin is effective, but many favour oral administration twice daily for 10 days. Amoxycillin remains the drug of choice for both AOM and ABS. A dose of 90 mg/kg/day is recommended in general, which should be effective for pneumococci with high-level penicillin resistance (this is particularly likely in children < 2 years of age, in day-care attendees, in cases with prior AOM within the past 6 months, and in children who have received antibiotics within the last 3 months).Alternative antibiotic choices are given in the guideline with recommendations for their specific indications. These antibiotics include amoxycillin-clavulanate, some cephalosporins, the macrolide/azalide and ketolide groups of agents and the respiratory fluoroquinolones.Conclusion: The guideline should assist rational antibiotic prescribing for URTIs. However, it should be updated when new information becomes available from randomised controlled trials and surveillance studies of local antibiotic susceptibility patterns.

Antibiotic Resistance in Pathogenic Streptococcus pneumoniaeIsolates in Turkey

Streptococcus pneumoniae causes various human infections such as meningitis, septicemia, otitis media, sinusitis, and pneumonia. Antibiotic resistance has already been reported with increasing frequency worldwide and is spreading. The earliest studies on pneumococcal antibiotic resistance go back to the late 1980s in Turkey. The resistance patterns have elevated with stepwise increments since then. By the beginning of 2005, approximately 40% of pneumococci were resistant to penicillin and nearly one-fifth of resistant isolates present high-level penicillin resistance. This proves that penicillin is still a good alternative for nonmeningeal infections. In addition, no ceftriaxone resistance have been reported in local Turkish studies, but cefuroxime, a second-generation cephalosporin, was recorded to have (10.8-20%) resistance rates.The most frequently assessed antibiotics other than penicillin in Turkish studies include erythromycin (4-19.4%), chloramphenicol (2-10%), clindamycin (2.5-13%) and tetracycline (13-28.6%) and all have various resistance profiles. On the other hand, nearly all or almost all of the isolates evaluated in Turkish studies are susceptible to rifampicin, quinolones, linezolid, quinupristin-dalfopristin and telithromycin. All these non-beta-lactam antibiotics except the tetracyclines are within acceptable limits of empirical approaches. Tetracycline must be used cautiously. In addition, trimethoprim sulfamethoxazole cannot be prescribed in probable pneumococcal infections since more than half of the isolates are nonsusceptible.

Presence of a mutation in ponA1 of Neisseria gonorrhoeae in numerous clinical samples resistant to various β-lactams and other, structurally unrelated, antimicrobials

The number of resistant strains in patients with Neisseria gonorrhoeae urethritis has been increasing, making effective treatment difficult. Chromosomally mediated penicillin-resistant N. gonorrhoeae arise through alterations in penicillin-binding proteins (PBPs) and a decrease in outer membrane permeability. To understand the occurrence of penicillin resistance in patients with N. gonorrhoeae infection, we performed this study. In addition, we studied minimum inhibitory concentrations (MICs) of antimicrobials against N. gonorrhoeae strains. We measured the MICs of penicillin G, other beta-lactams, and other kinds of antimicrobials against 53 clinical N. gonorrhoeae isolates from male patients with urethritis in Hyogo and Osaka, Japan. The ponA genes, encoding PBP 1 of these isolates, were sequenced. Of the 53 isolates tested, 41 strains showed some resistance to penicillin G. A mutation in the ponA (ponA1) gene was identified in 46 isolates. There was a tendency that ponA mutant (ponA1) in N. gonorrhoeae led to higher antimicrobial MICs of beta-lactam antimicrobial agents (including penicillin) than those of non-ponA mutants. However, we found lower than expected MICs of penicillin and beta-lactams even in ponA mutants. Therefore, we consider that detailed investigations for the further understanding of the effect of other genes, such as penC (which is reported to be related to ponA1 in achieving high-level penicillin resistance) should be our next step.

Pattern of Antibiotic Resistance of Streptococcus pneumoniae in a Hospital in the Eastern Province of Saudi Arabia

Internal Medicine Specialty Services Division, Dhahran Health Center, Saudi Aramco Medical Services Organization, Saudi Aramco, Dhahran, Saudi Arabia. The objective of the study was to evaluate the pattern of antibiotic resistance of Streptococcus pneumoniae at Saudi Aramco Medical Services Organization (SAMSO) in the Eastern Province of Saudi Arabia. We identified, retrospectively S. pneumoniae isolates from January 1999 to December 2002. Antimicrobial susceptibility and clinical data were collected and analyzed. A total of 162 isolates of S . pneumoniae were identified in the study period. Of these isolates, 94 (58%) isolates were obtained from out-patients and 68 (42%) were obtained from in-patients. Thirty-five percent of isolates were from blood, 46% from the respiratory tract, and the remainder were obtained from other sites. Of these isolates, 83 (51%) were penicillin-susceptible and the remaining 79 (48.8%) were not penicillin susceptible. High-level resistance to penicillin existed in 19.8% of the total isolates. Prevalence of resistance to erythromycin, tetracycline and trimethoprim-sulfamethoxazole was 25%, 29%, and 42% respectively. None of the isolates was resistant to vancomycin or ceftriaxone. However, 12% of the isolates showed multi-drug resistance.Streptococcus pneumoniae shows 19.8% high-level penicillin resistance and 12% multi-drug resistance. These findings call for wiser use of antibiotics.

Rates of antimicrobial resistance among common bacterial pathogens causing respiratory, blood, urine, and skin and soft tissue infections in pediatric patients.

Antimicrobial resistance patterns among the principal bacterial pathogens from infections of the respiratory tract, blood, skin and soft tissue, and urinary tract of pediatric patients from the USA, Canada, Germany, France, and Italy were studied using the The Surveillance Network (TSN) database. Among Streptococcus pneumoniae isolates from respiratory tract infections, the prevalence of high-level penicillin resistance (MIC>/=2 microg/ml) ranged from 1.1 (Italy) to 36.2% (USA); erythromycin resistance was higher, ranging from 13.4 (Germany) to 63.8% (France). The prevalence of beta-lactamase-positive Haemophilus influenzae among isolates from lower respiratory tract infections ranged from <10 (Italy and Germany) to 38.4% (USA). Among isolates from blood and skin and soft tissue infections, the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) ranged from 7.2% (Canada and Germany) to 27.3% (Italy). The prevalence of Escherichia coli and Klebsiella pneumoniae with putative extended-spectrum beta-lactamases among isolates from blood, urinary tract, and skin and soft tissue infections ranged from 0 (Germany and France) to 29.6% (Italy). With the exception of pseudomonal infections or infections with MRSA, amoxicillin-clavulanate retained moderate activity, whilst ceftriaxone and cefepime were the most effective broad-spectrum injectable agents. Meropenem was the most effective agent against Pseudomonas aeruginosa with <5% resistance. Low levels of resistance, along with acceptable safety profiles and the availability of convenient oral formulations, continue to support the use of ceftriaxone, cefepime, amoxicillin-clavulanate, and meropenem as viable options for the treatment of infections in pediatric patients.

Invasive pneumococcal disease in the Australian Capital Territory and Queanbeyan region: do high infant rates reflect more disease or better detection?

To describe the epidemiology of invasive pneumococcal disease in the Australian Capital Territory (ACT) and Queanbeyan region prior to the introduction of conjugate pneumococcal vaccines. Residents with sterile site isolates of Streptococcus pneumoniae from 1998 to 2000 were identified from a prospective bacteraemia surveillance project involving all ACT public hospitals, supplemented by retrospective laboratory-based detection of other sterile site isolates. Incidence of invasive pneumococcal disease was 15.2 cases per 105 per year, and 193.4 per 105 per year in infants under 2 years. Primary bacteraemia was significantly more common in infants and young children than in older subjects. Reduced penicillin susceptibility was observed in 9.6% of isolates, and no high-level penicillin resistance was observed. Infants in the ACT and Queanbeyan have a higher invasive pneumococcal disease incidence than similar populations worldwide. Better detection is the most likely explanation. This population would be ideal for studies of the 'real life' effectiveness of infant conjugate vaccination.

Nosocomial bloodstream infections due to viridans streptococci in haematological and non-haematological patients: species distribution and antimicrobial resistance

We studied the species distribution and antimicrobial susceptibility of viridans streptococci (VS) isolates causing nosocomial bloodstream infections (BSIs) in Finnish hospitals. Patients with nosocomial BSIs due to VS were identified through a hospital-wide prospective laboratory-based surveillance in two university and two regional hospitals during September 1998-August 2001. Isolates of VS were sent to the reference laboratory for species confirmation and antimicrobial susceptibility testing. A total of 2038 nosocomial BSIs were identified; 108 (5%) of the BSIs were caused by VS. Of the VS BSIs, 66% were in patients with a haematological malignancy, 14% in patients with a solid tumour and 18% in patients who had undergone surgery preceding the infection. The most common species group identified was Streptococcus mitis (82%). High-level penicillin resistance (> or = 4 mg/L) and cefotaxime resistance (> or = 4mg/L) were present in 5% and 4% of isolates, respectively; both were detected only in haematological patients. However, in non-haematological patients, resistance to erythromycin (17%), and reduced susceptibility to levofloxacin (14%) and penicillin (19%) were common. The resistance problems in VS are not limited to haematological patients. These findings may have significant clinical implications in the choice of both empirical antibiotic and antimicrobial prophylaxis regimens.