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Gatifloxacin phase IV surveillance trial (TeqCES study) utilizing 5000 primary care physician practices: report of pathogens isolated and susceptibility patterns in community-acquired respiratory tract infections.

Recently FDA-approved fluoroquinolones like gatifloxacin possess enhanced activity against Gram-positive pathogens such as Streptococcus pneumoniae. However, experience with adverse events among previously used fluoroquinolones has led to expanded post-marketing investigations of clinical efficacy and safety. An open-label gatifloxacin trial was initiated in early 2000, using 2795 (>15000 enrolled cases) primary care providers for treatment of community-acquired respiratory tract infections (CARTI) such as community-acquired pneumonia (CAP), acute bacterial exacerbation of chronic bronchitis (ABECB), acute sinusitis. Microbiology specimens and sputum slides were referred to a reference laboratory, pathogens identified and reference antimicrobial susceptibility tests performed. Results were classified by infection site, geographic census region and patient profile/demographics. The most frequent pathogens were: for CAP (n = 384)-S. pneumoniae (37%) > Hemophilus influenzae (31%) > Moraxella catarrhalis (13%); for ABECB (528)-H. influenzae (37%) > M. catarrhalis (26%) > S. pneumoniae (17%); and for sinusitis (2691)-M. catarrhalis (29%) > H. influenzae (24%) > S. pneumoniae (17%). H. parainfluenzae (ABECB) and S. aureus (sinusitis) were also commonly isolated. CAP S. pneumoniae isolates had significantly less high-level resistance (5% at > or =2 micro g/ml) than those isolates from ABECB or sinusitis (13-15%). United States census zone differences in S. pneumoniae resistance were identified (greatest in West or East South Central, South Atlantic). S. pneumoniae macrolide resistance was high (23-33%) and H. influenzae clarithromycin susceptibility was only 56-62%. beta-lactamase rates in H. influenzae and M. catarrhalis were 21-29% and 88-92%, respectively. Only one S. pneumoniae was not susceptible to gatifloxacin, and this new fluoroquinolone was fourfold more potent than levofloxacin (MIC(50,) 0.25 vs. 1 micro g/ml). This Phase IV surveillance trial (TeqCES) confirmed the clinical importance of S. pneumoniae, H. influenzae and M. catarrhalis in CARTI, and high fluoroquinolone potency/spectrum (>97% susceptible). beta-lactams and macrolides continue to be compromised by increasing resistances in pathogens isolated in these monitored primary care settings.

Adult↗

Response of biting midges (Diptera: Ceratopogonidae) to carbon dioxide, octenol, and light in southeastern Queensland, Australia.

The effect of 1-octen-3-ol (octenol) on catches of estuarine biting midges in encephalitis vector surveillance (EVS) traps was examined in southeastern Queensland. Octenol by itself was not attractive but appeared to act as a synergist with CO2 to increase catches of most species. For four of six species tested, a medium (about 6 mg/h) release rate of octenol captured the most individuals. Addition of light also increased the catch size of most species. Octenol in combination with CO2 could be used to enhance biting midge catch size, improving the sensitivity of surveillance for midges and the pathogens they vector.

Animals↗

Pathogen of occurrence and susceptibility patterns associated with pneumonia in hospitalized patients in North America: results of the SENTRY Antimicrobial Surveillance Study (2000).

Antimicrobial selection for patients diagnosed with pneumonia is a major therapeutic challenge and dilemma to the clinical practitioner. In the community setting, patients usually receive empiric oral therapy based upon multiple patient risk factors and locally prevalent pathogen susceptibilities. For patients admitted to the hospital with pneumonia, or who acquire pneumonia while in the hospital, therapy can be initially empiric and then become directed once culture and susceptibility results are known. The SENTRY Antimicrobial Surveillance Program since 1997, has monitored pathogen frequency and antimicrobial susceptibilities in hospitalized patients with pneumonia in North America. In this Study 2,712 pathogens were studied from 30 medical centers (25 in the United States and 5 in Canada). Over 30 species of organisms were recovered with Staphylococcus aureus comprising 28.0% of all isolates and with four other species (Pseudomonas aeruginosa 20.0%, Streptococcus pneumoniae 9.1%, Klebsiella spp. 7.5% and Haemophilus influenzae 7.3%) constituted 71.9% of isolates submitted. Methicillin (oxacillin)-resistant S. aureus accounted for 43.7% of all S. aureus isolates. Antimicrobials demonstrating significant (>80%) activity against S. aureus were: chloramphenicol (81.6%), tetracycline (91.4%), rifampin (96.4%) and quinupristin/dalfopristin (99.7%); and no isolate was resistant to glycopeptides or linezolid. North American isolates of P. aeruginosa were most susceptible to amikacin (93.7%) > tobramycin (90.2%) > meropenem (89.1%) > imipenem = piperacillin/tazobactam (85.6%) > piperacillin (82.1%) > cefepime (80.5%). Overall, 32.1% of S. pneumoniae were penicillin non-susceptible while erythromycin susceptibility was only 74.8%. Fluoroquinolones and recent generation cephalosporins retained excellent activity (gatifloxacin [99.2%] > levofloxacin = cefepime [98.8%] > ceftriaxone [97.2%]) against S. pneumoniae. Klebsiella spp. were 100.0% susceptible to the carbapenems (meropenem and imipenem) but extended spectrum beta-lactamases were detected at a rate of 5.4%. The beta-lactamase-positive rate in H. influenzae was 28.6% in North America (71.4% ampicillin-susceptible). The SENTRY Antimicrobial Surveillance Program continues to identify important North American patterns of pathogen frequency and resistance. Additionally, the provision of multi-year longitudinal data and associated reports allow for comparisons, which function as critical tools for effective patient management and antimicrobial interventions.

Anti-Bacterial Agents↗

A reusable model of pangenome selection informs optimal surveillance strategies over vaccine introductions.

BACKGROUND: The human pathogen Streptococcus pneumoniae is a major cause of disease, including pneumonia and meningitis. The introduction of Pneumococcal Conjugate Vaccines (PCVs) initially reduced the burden of disease through a reduction of colonisation by vaccine-targeted serotypes. However, since PCVs only target a proportion of pneumococcal serotypes, they shift intraspecific competition, eventually allowing non-targeted types to 'replace' vaccine types. Understanding the host and pathogen factors causing replacement is important for future vaccine development. Mechanistic understanding of vaccine replacement dynamics is crucial for forecasting and optimisation of genomic surveillance strategies to evaluate realised vaccine effectiveness. METHODS: We developed a mathematical model of the genomic and demographic factors which explain vaccine replacement, used this model to replicate serotype-frequency changes, and investigated cost-effective genomic surveillance strategies. We extended a forward-time model based on the Wright-Fisher model, developing a user-friendly model framework that describes the post-vaccine dynamics of S. pneumoniae populations. Our model describes vaccine replacement as a function of vaccine impact, immigration of new strains, and negative frequency-dependent selection (NFDS) on the accessory genome content. RESULTS: We used our model to study vaccine replacement in newly sequenced genomic surveillance data from Kathmandu (Nepal), and existing data from Massachusetts (US) and Southampton (UK), with distinct surveillance strategies. We showed that the model with NFDS better replicates replacement dynamics than a null model without NFDS, and that NFDS likely only acts on part of the S. pneumoniae accessory genome. We found consistent estimates for vaccination effectiveness across the different study locations and region-specific genes under NFDS, highlighting the importance of conducting genomic surveillance in each country of interest. By simulating data from the model, we showed that an optimal surveillance strategy prioritises per-sampling sample size over sampling frequency for small sampling budgets. CONCLUSIONS: Our model can be used to predict vaccine replacement dynamics after PCV introduction, and can be easily reapplied to analyse new data from vaccine introductions or new regions. Our model is available in the R package Stubentiger (Studying Balancing Evolution (NFDS) To Investigate Genome Replacement) on GitHub https://github.com/bacpop/Stubentiger .

Streptococcus pneumoniae↗

Trends in antimicrobial resistance among today's bacterial pathogens.

Resistance of nosocomial and community-acquired pathogens to antimicrobial agents is a serious problem with significant clinical consequences. Microbiologic surveillance data, such as those provided by the National Nosocomial Infections Surveillance System, supply information on current nosocomial pathogens in the United States. Many species show resistance to commonly used antimicrobials and, in many cases, it is emerging resistance. Resistance in many gram-negative bacteria is caused by beta-lactamase production. Escherichia coli, the leading nosocomial pathogen, is capable of hyperproducing TEM-1 beta-lactamase. A novel form of resistance in Klebsiella pneumoniae and E. coli is caused by extended-spectrum cephalosporinases. Many Enterobacteriaceae can be induced to produce group 1 beta-lactamase by exposure to broad-spectrum cephalosporins and other beta-lactams. Thirty percent of Haemophilus influenzae isolates are resistant to ampicillin because of beta-lactamase production. Issues of concern in gram-positive species include multiple antimicrobial resistance in methicillin-resistant Staphylococcus aureus, enterococci, and coagulase-negative staphylococci, and increasing beta-lactam resistance in Streptococcus pneumoniae. To minimize the development of resistance, antimicrobials must be administered judiciously, and infection-control practices must be instituted and followed.

Anti-Bacterial Agents↗

Global surveillance through PROTEKT: the first year.

The increasing antimicrobial resistance amongst bacterial pathogens causing community-acquired respiratory tract infections (CARTIs) necessitates surveillance at the local, regional, national and international levels to provide information to guide empiric antimicrobial therapy. PROTEKT (Prospective Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin) is a longitudinal, global, multicenter surveillance study designed to monitor the worldwide development of antimicrobial resistance and disseminate up-to-date information via the internet to assist in the choice of empiric therapy at the local level. In this paper, the results for the first year of PROTEKT are presented from a global perspective. Streptococcus pneumoniae, followed by Haemophilus influenzae and Moraxella catarrhalis, are the principal organisms responsible for the majority of CARTIs. The global prevalence of penicillin G resistance in S. pneumoniae has risen to an alarming 36.3% (high-level resistance 22.1%, intermediate-level 14.2%) with the highest prevalence found in Asia (68%). In all regions, macrolide resistance is greater than penicillin G resistance with a global prevalence rate of 31.2%. High resistance rates were also found for tetracycline (30.5%) and co-trimoxazole (43.9%), and multiresistance was found between penicillin G, macrolides, tetracycline and co-trimoxazole. The prevalence of beta-lactamase-producing H. influenzae and M. catarrhalis was found to be similar to previous reports. Macrolide resistance in S. pyogenes was 0.3% overall. Telithromycin demonstrated excellent in vitro activity against all organisms and is a potential new candidate for the empiric therapy of CARTIs. The first year of PROTEKT has provided valuable information on the prevalence of antimicrobial resistance of bacterial agents causing CARTIs that can be used for guiding empiric therapy and policies. The rapidly developing and geographically varying resistance observed in this study further emphasizes the need for accurate up-to-date surveillance data.

Acute Disease↗

Contemporary causes of skin and soft tissue infections in North America, Latin America, and Europe: report from the SENTRY Antimicrobial Surveillance Program (1998-2004).

The morbidity and cost for cure associated with skin and soft tissue infections (SSTIs) have recently become more complicated because of the increasing prevalence of multidrug-resistant pathogens associated with this healthcare problem. The SENTRY Antimicrobial Surveillance Program has been monitoring SSTI since 1997, and now presents data from 3 continents over a 7-year period (1998-2004). Isolates were tested by reference broth microdilution methods at a central laboratory using the Clinical and Laboratory Standards Institute (formerly the National Committee for Clinical Laboratory Standards) methods and interpretative criteria. The predominant pathogens included Staphylococcus aureus (ranked 1st in all geographic regions), Pseudomonas aeruginosa, Escherichia coli, and Enterococcus spp. A considerable variation in the methicillin (oxacillin)-resistant S. aureus rate was noted between countries and continents, with the overall rate highest in North America (35.9%) compared with Latin America (29.4%) and Europe (22.8%). Vancomycin-resistant Enterococcus spp. increased in Europe (4.1%) and North America (6.2%) during the period, but remained low and relatively unchanged in Latin America. Among the P. aeruginosa isolates tested, susceptibility to imipenem was much lower in Latin America (65.3%) compared with the other regions (80.7-88.7%), and resistance being associated with an increase in metallo-beta-lactamase-producing strains in Latin America and in some European countries. Multidrug-resistant strains of P. aeruginosa were also more of a concern in Latin America (24.7%) compared with Europe (10.8%) or North America (3.2%). Latin America also had the highest occurrence of extended-spectrum beta-lactamase-producing isolates among E. coli (15.1%) and Klebsiella spp. (48.0%) when compared with other regions. Continued surveillance of pathogen prevalence and antimicrobial resistance patterns should provide information that is important to improve empiric care particularly in the hospital environment.

Anti-Bacterial Agents↗

Increased stool sampling during a waterborne outbreak of cryptosporidiosis does not increase the detection of other faecal pathogens.

AIMS: To ascertain the effect of enhanced surveillance following an outbreak of waterborne cryptosporidiosis on the number of faecal specimens submitted to the local microbiology laboratory and the number positive for common enteric pathogens. The outbreak provided an opportunity to estimate the extent of routine under ascertainment of common enteric pathogens. METHOD: Retrospective search of the computerised microbiology system database for details of faecal examination requests for the period 26 April to 6 June in 1998 and 1999 (period of outbreak). RESULTS: Specimens were received from 378 community patients during the six week period 26 April to 6 June 1999. This was double that for the same period in 1998 (a non-outbreak year). Oocysts of Cryptosporidium parvum were detected in 59 patients, an eightfold increase compared with the same period in 1998. Despite the greater number of patients tested, the detection of other pathogens in patients with gastroenteritis was not altered when compared with the same period in the previous year. CONCLUSION: This study found no evidence of under ascertainment of gastrointestinal infection (common bacterial pathogens and rotavirus) by local general practitioners.

Adolescent↗

Study of infectious intestinal disease in England: rates in the community, presenting to general practice, and reported to national surveillance. The Infectious Intestinal Disease Study Executive.

OBJECTIVE: To establish the incidence and aetiology of infectious intestinal disease in the community and presenting to general practitioners. Comparison with incidence and aetiology of cases reaching national laboratory based surveillance. DESIGN: Population based community cohort incidence study, general practice based incidence studies, and case linkage to national laboratory surveillance. SETTING: 70 general practices throughout England. PARTICIPANTS: 459 975 patients served by the practices. Community surveillance of 9776 randomly selected patients. MAIN OUTCOME MEASURES: Incidence of infectious intestinal disease in community and reported to general practice. RESULTS: 781 cases were identified in the community cohort, giving an incidence of 19.4/100 person years (95% confidence interval 18.1 to 20.8). 8770 cases presented to general practice (3.3/100 person years (2.94 to 3.75)). One case was reported to national surveillance for every 1.4 laboratory identifications, 6.2 stools sent for laboratory investigation, 23 cases presenting to general practice, and 136 community cases. The ratio of cases in the community to cases reaching national surveillance was lower for bacterial pathogens (salmonella 3.2:1, campylobacter 7.6:1) than for viruses (rotavirus 35:1, small round structured viruses 1562:1). There were many cases for which no organism was identified. CONCLUSIONS: Infectious intestinal disease occurs in 1 in 5 people each year, of whom 1 in 6 presents to a general practitioner. The proportion of cases not recorded by national laboratory surveillance is large and varies widely by microorganism. Ways of supplementing the national laboratory surveillance system for infectious intestinal diseases should be considered.

Adolescent↗

Avian influenza: are our feathers ruffled?

During the past century, three major influenza pandemics took place, leading to a devastating number of deaths. Pandemics occur through the emergence of a new strain of influenza virus that can infect humans, to which there is little pre-existing immunity and which spreads easily from human to human. The H5N1 influenza virus has the potential of becoming a pandemic virus, since it can infect humans and is highly pathogenic. All that remains is the final step of acquiring the genetic material to enable efficient human-to-human transmission. Therefore, the World Health Organization (WHO) has declared pandemic alert phase 3, the last phase before there is actual evidence of increased and efficient human-to-human transmission. In addition, every case of transmission of an avian influenza virus to humans is regarded by WHO as a cause for heightened alertness and surveillance. The circulation of highly pathogenic avian influenza viruses in large numbers among the poultry population in a growing number of countries is a major concern. Since the influenza viruses are highly unstable, the co-circulation of highly pathogenic animal viruses with human viruses may create opportunities for different species-specific viruses to exchange genetic material, giving rise to a new influenza virus to which humans would have little, if any, protective immunity. In this article, we highlight the current avian influenza situation from its different aspects with a special focus on the Hajj since we host over 2 million pilgrims a year in the holy cities of Mekkah and Medina.

Animals↗

Prevalence of important pathogens and antimicrobial activity of parenteral drugs at numerous medical centers in the United States, I. Study on the threat of emerging resistances: real or perceived? Fluoroquinolone Resistance Surveillance Group.

Forty-three medical centers participated in a national (United States) surveillance study of parenteral antimicrobial agents as empiric therapy of pathogens isolated from blood, skin wounds, respiratory tract, and urine (> 8500 strains, 200 per laboratory). All laboratories tested each organism by the same reagent disks and/or Etest (AB Biodisk, Solna, Sweden) strips. Quality control results validated all laboratories for analyses. The most common isolates were Escherichia coli (1648), Staphylococcus aureus (1408), Pseudomonas aeruginosa (1003), Klebsiella species (792), and the enterococci (684). Among the tested drugs the percent susceptible rates observed were ofloxacin (83.4%), ciprofloxacin (82.0%), and cefuroxime (62.9%) tested against all organisms; cefazolin (54.7%) and ceftazidime (76.7%) tested against all nonfastidious aerobes; gentamicin (91.2%), imipenem (95.3%), ticarcillin-clavulanate (78.2%), and ceftriaxone (66.2%) tested against Gram-negative organisms only; and vancomycin (97.9%) and erythromycin (49.2%) tested against Gram-positive aerobes. Several drug-resistant species appear to be emerging or increasing in the United States: (a) vancomycin-resistant enterococci (7.9%, mostly Enterococcus faecium); (b) oxacillin-resistant S. aureus (21.0%); (c) third-generation cephalosporin-resistant Enterobacteriaceae, including E. coli and Klebsiella species with extended-spectrum beta-lactamases (approximately 1.3%-8.6%); (d) penicillin-resistant Streptococcus pneumoniae (17.8%); and (e) ciprofloxacin-resistant P. aeruginosa (14.9%). Fluoroquinolone resistance among the enteric bacilli was confirmed in 60 of 66 referred strains (0.8% of total strains), and cross-resistance was high among ciprofloxacin, ofloxacin, lomefloxacin, fleroxacin, and norfloxacin (98.3%-100%). Seventeen strains of fluoroquinolone-resistant enteric bacilli (0.2% of total) also harbored an ESBL and resistance to aminoglycosides. Clonal spread within medical centers was observed with the ESBL-producing Klebsiella pneumoniae. This national clinical isolate data base continues to demonstrate broad fluoroquinolone efficacy (ofloxacin > ciprofloxacin) against hospital-based pathogens and many strains of emerging resistant bacteria. Continued US surveillance studies are urged to monitor emerging antimicrobial resistance and to guide interventions to minimize its occurrence.

Anti-Bacterial Agents↗

Whole-genome sequencing, strain composition, and predicted antimicrobial resistance of Streptococcus pneumoniae causing invasive disease in England in 2017-20: a prospective national surveillance study.

BACKGROUND: Surveillance of the invasive disease burden caused by Streptococcus pneumoniae in England is performed by the UK Health Security Agency (UKHSA). In 2017, UKHSA switched from phenotypic methods to whole-genome sequencing (WGS) approaches for pneumococcal surveillance. Here, we present the first results of national WGS surveillance, up to the start of the COVID-19 pandemic, with the aim of describing the population genomics of this important pathogen. METHODS: We examined prospective national surveillance data from England, using bacterial isolates from cases of invasive pneumococcal disease (IPD) submitted to the national reference laboratory at UKHSA. A bioinformatic pipeline was developed to quality control WGS data and routinely report species and serotype. We assembled isolate data, assigned global pneumococcal sequencing clusters (GPSCs), and predicted antimicrobial resistance (AMR) profiles for isolates that passed further quality control. We collected additional data on patient outcomes and characteristics using enhanced surveillance questionnaires completed by patients' general practitioners. We used logistic regression analysis to assess the effects of various genomic and patient characteristics on the outcomes of IPD. FINDINGS: In England, between July 1, 2017, and Feb 29, 2020, there were 15 400 cases of IPD. From these cases, 13 749 (89·3%) isolates were sequenced, passed quality control, and were included in analyses. Serotype diversity was high during the study period, with 2751 (20%) isolates serotyped as 13-valent pneumococcal conjugate vaccine (PCV13) types, whereas serotype 8 was the most prevalent serotype (n=3074 [22·4%]) overall. There were 157 GPSCs within the collection, with GSPC3 the most common, encompassing 98·7% (3033 of 3074) of serotype 8 isolates. Most isolates (n=10 198 [74·2%]) did not contain AMR-associated genes. Resistance to co-trimoxazole was the most frequently predicted resistance (n=2331 [17%]), followed by resistance to tetracycline (n=1199 [8·7%]) and β-lactams (n=1149 [8·4%]). Logistic regression analysis found the presence of AMR-associated genes significantly increased the odds of patient death (odds ratio 1·18, 95% CI 1·01-1·38). Some GPSCs were also associated with a significant increase in the odds of patient death, such as GPSC12 (1·88, 1·48-2·38). Isolates from 2018 were associated with a significant increase in the odds of patient death (1·12, 1·00-1·25), whereas younger patient age was significantly associated with a reduction in the odds of patient death compared with being aged 85 years or older. INTERPRETATION: WGS-based surveillance has allowed us to interrogate country-wide population dynamics driving changes in pneumococcal serotype frequency. Here, we observe a stable but diverse population before the COVID-19 pandemic restrictions were enforced in England, with low rates of AMR. These findings will provide the baseline for pandemic and post-pandemic data, to collectively inform implementation and development of the vaccination programme within the country. FUNDING: None.

Streptococcus pneumoniae↗

Whole genome sequencing and phylogenetic classification accelerate the implementation of respiratory syncytial virus genomic surveillance in Canada: a pilot study.

UNLABELLED: Whole genome sequencing (WGS) has emerged as a powerful tool to facilitate the study of existing and emerging infectious diseases. WGS-based genomic surveillance provides information on the genetic diversity and tracks the evolution of important viral pathogens, including respiratory syncytial virus (RSV). Multiplex tiling polymerase chain reaction (PCR) assays have been used to facilitate sequencing of a variety of pathogens in support of genomics-based surveillance initiatives. We developed, optimized, and implemented multiplex tiling PCR assays for RSVA and RSVB capable of generating near-complete genomes in the majority of contemporaneous specimens tested. A pilot data set comprising 52 RSVA and 37 RSVB genomes derived from Canadian clinical specimens during the 2022-2023 respiratory virus season was used to perform phylogenetic analyses using both near-complete genome and glycoprotein (G) sequences. Overall, the RSV phylogenetic tree built with whole genomes showed identical lineage clusters as compared to the G gene but was more discriminatory. Moreover, the availability of complete genomes enables the identification of a broader range of mutations. For instance, mutations identified in the fusion protein among Canadian isolates tested here, including S377N, K272M, S276N, S211N, S206I, and S209Q, could affect the efficacy of current vaccines or antiviral-based therapeutics. In conclusion, our work reinforces other recent studies demonstrating the utility of multiplex tiling PCR assays to facilitate high-throughput WGS of RSV, which is capable of supporting enhanced genomic surveillance initiatives, as well as the more comprehensive genomic analyses required to inform public health strategies for the development and usage of vaccines and antiviral drugs. IMPORTANCE: We present assays to efficiently sequence genomes of RSVA and RSVB. This enables researchers and public health agencies to acquire high-quality genomic data using rapid and cost-effective approaches. Genomic data-based comparative analysis can be used to conduct surveillance and monitor circulating isolates for efficacy of vaccines and antiviral therapeutics.

Humans↗

Frequency of pathogen occurrence and antimicrobial susceptibility among community-acquired respiratory tract infections in the respiratory surveillance program study: microbiology from the medical office practice environment.

Continuing problems of antimicrobial resistance have prompted the initiation of several surveillance programs. Few, if any, of these programs focus on community-acquired respiratory tract infections seen in routine office-based practices. The Respiratory Surveillance Program (RESP; 1999-2000) in 674 community-based physician office practices in the United States determined the frequency of potential bacterial pathogens including Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis in patients diagnosed clinically with community-acquired pneumonia, acute exacerbations of chronic bronchitis, and sinusitis throughout all 9 US census/geographic regions. Susceptibility to the penicillins (ampicillin, penicillin), oral cephalosporins, fluoroquinolones (gatifloxacin, levofloxacin, ciprofloxacin), macrolides (erythromycin, azithromycin, clarithromycin), tetracycline, and trimethoprim/sulfamethoxazole was determined by reference methods. Patients were required to have a culturable focus of infection, and specimens were immediately sent to a reference laboratory. Among 22,689 total specimens (610 community-acquired pneumonia, 4,779 acute exacerbation of chronic bronchitis, 16,213 sinusitis, 1,087 other), H influenzae was the most commonly isolated organism from patients with community-acquired pneumonia (38%) and acute exacerbation of chronic bronchitis (35%) in all nine geographic regions. S pneumoniae was isolated in 18% of community-acquired pneumonia cases, 13% of acute exacerbation of chronic bronchitis cases, and 11% of sinusitis cases. M catarrhalis was most commonly isolated from the nasopharynx of patients with sinusitis (29%). High-level resistance to penicillin (2 microg/mL or greater; 16% overall) and the macrolides (32% to 35%) among S pneumoniae varied both with site of infection and with geographic region. The greatest resistance was observed among isolates from the nasopharynx of patients with sinusitis and from patients from the East South Central or South Atlantic regions of the United States. Although the susceptibility of H influenzae and M catarrhalis to the tested antimicrobials did not vary with the type of infection, beta-lactamase-mediated resistance to ampicillin among H influenzae ranged from 15% in New England to 32% in the East South Central region. The fluoroquinolones were highly active against these cultured isolates from community-acquired respiratory tract infection patients, with >99% of all S pneumoniae, H influenzae, and M catarrhalis strains susceptible to gatifloxacin (MIC(90), 0.5 microg/mL) and levofloxacin (MIC(90), 2 microg/mL). The extended-spectrum fluoroquinolones appear well suited for community-acquired respiratory tract infection therapy, including pathogens other than pneumococcus, H influenzae, and M catarrhalis.

Adolescent↗

Simultaneous discrimination between 15 fish pathogens by using 16S ribosomal DNA PCR and DNA microarrays.

We developed a DNA microarray suitable for simultaneous detection and discrimination between multiple bacterial species based on 16S ribosomal DNA (rDNA) polymorphisms using glass slides. Microarray probes (22- to 31-mer oligonucleotides) were spotted onto Teflon-masked, epoxy-silane-derivatized glass slides using a robotic arrayer. PCR products (ca. 199 bp) were generated using biotinylated, universal primer sequences, and these products were hybridized overnight (55 degrees C) to the microarray. Targets that annealed to microarray probes were detected using a combination of Tyramide Signal Amplification and Alexa Fluor 546. This methodology permitted 100% specificity for detection of 18 microbes, 15 of which were fish pathogens. With universal 16S rDNA PCR (limited to 28 cycles), detection sensitivity for purified control DNA was equivalent to <150 genomes (675 fg), and this sensitivity was not adversely impacted either by the presence of competing bacterial DNA (1.1 x 10(6) genomes; 5 ng) or by the addition of up to 500 ng of fish DNA. Consequently, coupling 16S rDNA PCR with a microarray detector appears suitable for diagnostic detection and surveillance for commercially important fish pathogens.

Animals↗

The value of surveillance cultures in neutropenic patients receiving selective intestinal decontamination.

230 neutropenic episodes in 84 patients with acute myeloid leukemia receiving selective intestinal decontamination were studied to evaluate the ability of surveillance cultures to monitor the efficacy of microbial suppression, to identify causative organisms in case of fever, and to predict infection due to potential pathogens (i.e. Staphylococcus aureus and aerobic Gram-negative bacteria). Most cultures became negative soon after the administration of prophylactic antibiotics and there were only few persistent colonizations. 14 potential pathogens resistant to the intestinal decontamination regimen were isolated in surveillance cultures, none of which caused infection. Of the 212 febrile episodes, only 22 were caused by a microbiologically documented infection with potential pathogens. Most microbiologically documented infections were caused by organisms not routinely identified by surveillance cultures, indicating efficient selective intestinal decontamination. Only 9 (41%) of the 22 infections with potential pathogens were predicted by surveillance cultures. We conclude that surveillance cultures are of limited use in predicting infection or identifying causative organisms of fever in neutropenic patients receiving selective intestinal decontamination. However, they are useful in monitoring the efficacy of microbial suppression. One set of surveillance cultures each week after the disappearance of potential pathogens would be sufficient.

Adult↗

Community-acquired antimicrobial resistance: is it controllable?

Antimicrobial agents were introduced into medical use about 50 years ago. Since then, the prevalence of antimicrobial resistance in community-acquired pathogens has increased rapidly worldwide. The relationship between antibiotic use and resistance is strongly supported by data from several studies. In Spain, the resistance rates for community-acquired pathogens are among the highest in Europe and coincide with a high consumption of antimicrobial agents. In contrast, in Finland, after a nationwide reduction in the use of macrolides for outpatient therapy, there has been a significant decline in the frequency of erythromycin resistance among group A streptococcal isolates. The control of community-acquired antimicrobial resistance is a challenge for the future and will require the early detection of resistance genes through global and local surveillance, prompt containment of resistant pathogens, and judicious use of antimicrobials.

Anti-Bacterial Agents↗

Comparison of the activity of two broad-spectrum cephalosporins tested against 2,299 strains of Pseudomonas aeruginosa isolated at 38 North American medical centers participating in the SENTRY Antimicrobial Surveillance Program, 1997-1998.

Pseudomonas aeruginosa is an important nosocomial pathogen. Resistance to certain beta-lactam antimicrobial agents among P. aeruginosa is increasing. The SENTRY Antimicrobial Surveillance Program was designed to employ a network of hospitals in the United States, Canada, Latin America, and Europe to monitor the predominant bacterial and fungal pathogens and antimicrobial susceptibility patterns associated with community-acquired and nosocomial bloodstream, respiratory tract, wound, and urinary tract infections. The purpose of this analysis of SENTRY results was to extract information on the current North American susceptibility pattern of P. aeruginosa for two antipseudomonal cephalosporins, ceftazidime, and cefepime. Clinical isolates were provided by 30 centers in the United States (grouped into five regions) and eight centers in Canada. Susceptibility testing was performed at a central reference laboratory by using broth microdilution methods and interpretive criteria specified by the National Committee for Clinical Laboratory Standards. Of the 34, 530 North American bacterial isolates tested during 1997 and 1998, 2299 (6.7%) were P. aeruginosa. There were no substantial differences in regional rates of P. aeruginosa susceptibility to ceftazidime (range 78.8-81.9%) or cefepime (range 80.0-83.4%) The percentage of resistant isolates among the 1784 United States isolates was 13.3% for ceftazidime versus 7.1% for cefepime (p < 0.05). It is essential to continue surveillance of the in vitro efficacy of these and other beta-lactam agents against P. aeruginosa because of the clinical importance of these safe and broad-spectrum cephems used alone or in combination in current clinical practice.

Cefepime↗