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PubMed2002

The pulmonary physician in critical care * 4: Nosocomial pneumonia.

Much progress has been made in the understanding of nosocomial pneumonia but important issues in diagnosis and treatment remain unresolved. The controversy over diagnostic tools should be closed. Instead, every effort should be made to increase our ability to make valid clinical predictions about the presence of ventilator associated pneumonia and to establish criteria to guide restricting empirical antimicrobial treatment without causing patient harm. More emphasis must be put on local infection control measures such as routine surveillance of pathogens, definition of controlled policies of antimicrobial treatment, and effective implementation of strategies of prevention.

Adolescent↗
PubMed2026

Genetic diversity and recombination of NA-PRRSV field strains in Vietnam: Implications for vaccine efficacy.

Porcine reproductive and respiratory syndrome (PRRS) causes severe reproductive losses in pregnant sows and piglets, resulting in substantial economic impact on the swine industry worldwide. However, due to the significant genetic diversity and rapid evolutionary changes of the pathogen, continuous surveillance and detailed genetic analysis of circulating strains are essential. The current study aimed to evaluate the genetic diversity of the hypervariable (HV) region of non-structural protein 2 (nsp2) among North American PRRSV strains isolated from swine farms in Vietnam. Phylogenetic analysis and multiple sequence alignment were conducted to determine subtype classification and assess genetic variability. A total of 48 field isolates were obtained, of which 12.5% belonged to classical NA-PRRSV, 16.6% to NADC30-like and 70.9% to HP-PRRSV, primarily distributed across sublineages 1.4, 5.1, 8.7 and 8.9. Amino acid comparisons found multiple insertions, deletions and substitutions at various positions within the hypervariable region of nsp2. The study revealed substantial genetic variation in the HV region of nsp2 among NA-PRRSV field strains, largely associated with recombination and immune escape. These findings highlight epidemiological risks to vaccine efficacy and underscore the need for continuous molecular surveillance to support effective PRRSV control in Vietnam.

PRRSV↗
PubMed2002

UL16-binding proteins, novel MHC class I-related proteins, bind to NKG2D and activate multiple signaling pathways in primary NK cells.

The UL16-binding proteins (ULBPs) are a novel family of MHC class I-related molecules that were identified as targets of the human CMV glycoprotein, UL16. We have previously shown that ULBP expression renders a relatively resistant target cell sensitive to NK cytotoxicity, presumably by engaging NKG2D, an activating receptor expressed by NK and other immune effector cells. In this study we show that NKG2D is the ULBP counterstructure on primary NK cells and that its expression is up-regulated by IL-15 stimulation. Soluble forms of ULBPs induce marked protein tyrosine phosphorylation, and activation of the Janus kinase 2, STAT5, extracellular signal-regulated kinase, mitogen-activated protein kinase, and phosphatidylinositol 3-kinase (PI 3-kinase)/Akt signal transduction pathways. ULBP-induced activation of Akt and extracellular signal-regulated kinase and ULBP-induced IFN-gamma production are blocked by inhibitors of PI 3-kinase, consistent with the known binding of PI 3-kinase to DAP10, the membrane-bound signal-transducing subunit of the NKG2D receptor. While all three ULBPs activate the same signaling pathways, ULBP3 was found to bind weakly and to induce the weakest signal. In summary, we have shown that NKG2D is the ULBP counterstructure on primary NK cells and for the first time have identified signaling pathways that are activated by NKG2D ligands. These results increase our understanding of the mechanisms by which NKG2D activates immune effector cells and may have implications for immune surveillance against pathogens and tumors.

Antibodies, Monoclonal↗
PubMed2004

[Resistance surveillance of common community respiratory pathogens isolated in China, 2002 - 2003].

OBJECTIVE: To investigate antimicrobial resistance of common community respiratory pathogens isolated in China, 2002 - 2003. METHODS: 779 strains of Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Group A beta-haemolytic Streptococci and oxacillin-susceptible Staphylococcus aureus (MSSA) were isolated from patients with community-acquired respiratory tract infections at 5 hospitals in China from April 2002 to 2003. Meanwhile, 185 strains of S. pneumoniae, H. influenzae and M. catarrhalis were isolated from nasopharynx swabs at 2 day-care centers in Beijing. Agar dilution method was used to determine the minimal inhibitory concentration (MICs) of cefprozil and other 9 antibiotics against these strains. RESULTS: The prevalence of penicillin-intermediate S. pneumoniae (PISP) was 23.9% and that of penicillin-resistant S. pneumoniae (PRSP) was 22.7% at 5 cities in China. The prevalence of PISP were 44.1% in Hangzhou, 26.2% in Wuhan, 21.5% in Shenyang, 20.8% in Shanghai, 18.5% in Beijing, and 12.7% at day-care centers in Beijing;the prevalance of PRSP were 34.9% in day-care centers, 31.9% in Shanghai, 27.9% in Wuhan, 22.1% in Hangzhou, 13.8% in Shenyang and 8.6% in Beijing. The susceptible rate of levofloxacin in S. pneumoniae was 96.3%. 9.5% of H. influenzae and 87.4% of M. catarrhalis produced beta-lactamases. The susceptibility of amoxicillin/clavulanate, cefaclor, cefprozil, cefuroxime, ceftriaxone, azithromycin, and levofloxain in these two species ranged from 96.4% to 100%. The resistance rate of azithromycin in S. pneumoniae was higher than 60%. Cefprozil MICs against PISP, Group A beta-haemolytic Streptococci and MSSA were 4 - 16 fold lower than cefaclor. CONCLUSIONS: Antimicrobial resistance in respiratory pathogens, especially S. pneumoniae is increasing. It brings concerns that high macrolide resistance was found in gram-positive cocci. Cefprozil was more active than cefaclor against respiratory pathogens.

Anti-Bacterial Agents↗
PubMed2004

[Characteristics and therapeutic strategies of nosocomial pneumonia in postoperative patients with acute hypertensive intracerebral hemorrhage].

OBJECTIVE: To investigate the characteristics of postoperative nosocomial pneumonia in patients with acute hypertensive intracerebral hemorrhage after evacuation of hematoma and the strategies of prevention and treatment. METHODS: Retrospective analysis was performed on the clinical data of surgically treated patients with acute hypertensive intracerebral hemorrhage in the Department of Neurosurgery from 2000 to 2003. The patients were divided into a group who developed nosocomial pneumonia to compare with a group who did not. Sputum was cultured B and drug sensitivity of isolated bacteria was performed. Appropriate treatment measures were given according to clinical manifestations. RESULTS: In 112 post operative patients with acute hypertensive intracerebral hemorrhage, nosocomial pneumonia developed in 29 patients (25.89%), and 65.99% of microorganisms isolated from respiratory secretion was Gram-negative bacteria. The predominant bacteria were Pseudomonas aeruginosa and Staphylococcus aureus. The mortality was 34.48% (10/29 cases). The prognosis of patients with nosocomial pneumonia was worse than the controls (7.23%, 6/83 cases, P<0.01). CONCLUSION: The preventive and therapeutic strategies for nosocomial pneumonia in postoperative patients with acute hypertensive intracerebral hemorrhage include reduction of risk-factors, surveillance of pathogens, rational use of antibiotics, respiratory and nutrition support, and so on.

Adult↗
PubMed1977

[Surveillance of drug resistance in pathogenic enterobacteria in Algeria. I. Study of the resistance of major and minor Salmonella species to antibiotics in 1973-1974].

901 Salmonella strains were examined in our laboratory between October 1973 and August 1974 for their sensitivity to antibiotics. The aim of this study was, on the one hand to detect the possible emergence of drug resistance in strains of Salmonella responsible for typhoid and paratyphoid fevers; on the other hand to follow up, as closely as possible, the occurrence of drug resistance in strains of other Salmonella serotypes isolated in infant and child populations; and, in addition, to awaken practitioners to the problems inherent to the widespread use of antibiotics in these diseases. The 752 typhoid and paratyphoid bacilli strains were found to be drug sensitive with the exception of one Salmonella typhi isolate bearing a R-plasmid coding for resistance to six antibiotics. 91% of the other Salmonella serotypes strains showed resistance to 3 - 7 antibiotics including a number of the latest in use. These data are discussed and a case is made for standardization in the treatment of typhoid fever and review of the use of antibiotics against salmonelloses in infants and young children.

Algeria↗
PubMed2003

Development of sensitive, high-throughput one-tube RT-PCR-enzyme hybridisation assay to detect selected bacterial fish pathogens.

Bacterial monitoring and surveillance is critical for the early detection of pathogens to avoid the spread of disease. To facilitate this, an efficient, high-performance and high-throughput method to detect the presence of femotgram amounts of ribosomal RNA from 4 bacterial fish pathogens: Aeromonas salmonicida; Tenacibaculum maritimum (formerly Flexibacter maritimus); Lactococcus garvieae; and Yersinia ruckeri was developed. The system uses NucleoLink strips for liquid- and solid-phase PCR in 1 tube, to perform RT-PCR-enzyme hybridisation assays (RT-PCR-EHA) detecting 4 fg or less of rRNA from pure cultures and between 1 and 9 CFU per 200 microl sample volume from selective-enrichment culture media. The liquid-phase amplicons were visualised by gel electrophoresis and the solid-phase amplicons detected using internal probes and visualised using colorimetric detection and p-nitrophenylphosphate.

Aeromonas↗
PubMed2026

Advancing One Health genomics in Africa: opportunities and challenges for outbreak and antimicrobial resistance control.

SUMMARYAfrica's ongoing struggles with emerging epidemics and antimicrobial resistance (AMR) underscore the urgency of integrating pathogen genomics and surveillance systems into the continent's One Health strategy, particularly given the existing limitations in preparedness and technological resources. This review brings together current evidence on the growth of sequencing infrastructure, the development of regional genomic hubs, and the establishment of governance frameworks, while identifying critical challenges in data integration, bioinformatics capacity, and sustainable financing. Special focus is placed on the lack of African-based genomic data, with our analysis showing that only 1.82% of the global total is available. Case studies illustrate the immense potential and importance of pathogen genomics, giving policymakers a tangible sense of its impact. These examples demonstrate how genomic technologies integrated with artificial intelligence (AI) are transforming outbreak response, AMR surveillance, and stewardship programs by enabling early detection of zoonotic threats, mapping transmission pathways, and guiding vaccine development. However, to fully realize this scientific intel, it is essential to embed One Health pathogen surveillance within strong policy and system frameworks to ensure the translation of technical progress into lasting institutional capacity and sustainable impact. Long-term implementation depends on coordinated investment and advocacy across four interdependent pillars: data architecture, governance and sovereignty, human capital, and technical capacity.

Humans↗
PubMed2002

Population biology of emerging and re-emerging pathogens.

Emerging and re-emerging pathogens present a huge challenge to human and veterinary medicine. Emergence is most commonly associated with ecological change, and specific risk factors are related to the type of pathogen, route of transmission and host range. The biological determinants of host range remain poorly understood but most pathogens can infect multiple hosts, and three-quarters of emerging human pathogens are zoonotic. Surveillance is a key defence against emerging pathogens but will often need to be integrated across human, domestic animal and wildlife populations.

Animals↗
PubMed2003

Susceptibility trends of haemophilus influenzae and Moraxella catarrhalis against orally administered antimicrobial agents: five-year report from the SENTRY Antimicrobial Surveillance Program.

The assessment of orally administered antimicrobial susceptibilities of common pathogens that cause community-acquired respiratory tract infections (CARTI) has become exceedingly important due to the number of office visits for this indication. Numerous local, regional and global studies have documented the susceptibilities of Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis, the most common CARTI pathogens. SENTRY Antimicrobial Surveillance Program sites in North and Latin America, and Europe were requested to send a combined total of 100 isolates of these pathogens to the local monitor for reference broth microdilution testing (1997-2001). This study compared the susceptibility profiles of H. influenzae and M. catarrhalis isolates (13,370 strains) from the three geographic regions over a five year period. beta-lactamase mediated ampicillin resistance among H. influenzae was highest among North American isolates (27.9%) compared to Latin America and Europe (16.2 to 16.3%), although it was noted that during the five year study period, ampicillin resistance was steadily increasing in the latter two regions. Cefprozil (84.3% susceptible) and clarithromycin (81.1% susceptible) were also less active against North American H. influenzae isolates. Latin American isolates were much less susceptible to trimethoprim/sulfamethoxazole (T/S; 59.3%) compared to the other regions (75.8 to 78.6%). M. catarrhalis isolates were also significantly less susceptible to T/S in Latin America (10.5% resistance). The production of beta-lactamase enzymes among the M. catarrhalis isolates exceeded >95% in all three regions during the five year period. The fluoroquinolones (FQ) remained very active against these two respiratory pathogens with rare isolates with elevated FQ MIC results. It is apparent from this investigation that many commonly prescribed empiric treatments remain viable therapeutic options for CARTI caused by these two Gram-negative respiratory tract pathogens.

Administration, Oral↗
PubMed2001

Antibacterial activity of 41 antimicrobials tested against over 2773 bacterial isolates from hospitalized patients with pneumonia: I--results from the SENTRY Antimicrobial Surveillance Program (North America, 1998).

Pneumonia is the second most frequent cause of nosocomial infection, and hospitalization frequently is needed for community-acquired pneumonia. Knowledge of causative pathogens through periodic surveillance, and their prevailing antimicrobial susceptibility patterns becomes paramount in choosing appropriate empiric therapy. The SENTRY Antimicrobial Surveillance Program, tracks pathogen distribution worldwide since 1997 and documents emerging resistance to a wide range of antimicrobial agents. During the respiratory disease season in 1998, each of 30 medical centers (25 in the United States [US], and five in Canada [CAN]) contributed 100 consecutive isolates obtained from hospitalized patients with suspected pneumonia. The 2773 organisms, processed by the monitor consisted of a total of 35 species, with Staphylococcus aureus comprising 25.6% of all isolates and five other species (Pseudomonas aeruginosa 18.7%, Haemophilus influenzae 9.4%, Streptococcus pneumoniae 7.8%, Klebsiella spp. 7.0%, and Enterobacter spp. 6.7%) making up almost 50% of the total. In the US, pneumococci (8.5%) were more prevalent than in CAN (4.1%; p = 0.001). The US isolates of S. pneumoniae were variably susceptible to penicillin (76.8%), with non-susceptible strains demonstrating greater levels of cross resistance to macrolides (31.8%), cefepime (9.0%) and cefotaxime (6.8%), but remaining susceptible to gatifloxacin and quinupristin/dalfopristin. H. influenzae and Moraxella catarrhalis were generally ampicillin-resistant, 40.4-44.4% and 93.7-95.7%, respectively. P. aeruginosa remained very susceptible to amikacin (91.3-93.8%) > tobramycin > meropenem > piperacillin/tazobactam > gentamicin > piperacillin > cefepime (80.0-81.8%). Extended spectrum beta-lactamase phenotypes among the Klebsiella spp. were isolated from five medical centers in the US and were 4.8-6.0% overall; a rate similar to the previous year. Among the US isolates of Enterobacter spp., only 77.6% and 79.6% were susceptible to ceftazidime and cefotaxime, respectively, but >90% were inhibited by cefepime, imipenem, meropenem, aminoglycosides, and fluoroquinolones. Isolates from CAN were generally more susceptible, except for Pseudomonas isolates, where resistance to aminoglycosides, fluoroquinolones and imipenem was greater. The SENTRY Program results outline important national differences in the frequencies of pathogen occurrence, but more importantly, identify unstable patterns of resistance to available antimicrobial drugs, and serves as a reference for results of other local, national or international investigations.

Adolescent↗
PubMed2004

Antimicrobial susceptibility to levofloxacin and other antibacterial agents among common respiratory pathogens-a Brazilian perspective from the GLOBAL Surveillance Initiative 2001-2002.

The GLOBAL (Global Landscape On Bactericidal Activity of Levofloxacin) Surveillance programme monitored antimicrobial susceptibility patterns of the key respiratory tract pathogens Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis collected in Brazil during 1997-1998, 1999-2000 and 2001-2002. Penicillin and azithromycin resistance among S. pneumoniae strains increased from 1997-1998, reaching 7.9% and 9.5%, respectively, in 2001-2002. Although decreasing by 4.9% since the previous study, trimethoprim-sulphamethoxazole resistance remained high at 33.7%. Concurrent resistance to penicillin, azithromycin and trimethoprim-sulphamethoxazole was seen in 2.9% of the S. pneumoniae isolates collected. Levofloxacin remained extremely active against S. pneumoniae, with 0.3% resistance reported in 1997-1998 and 0% resistance in 1999-2000 and 2001-2002. beta-Lactamase production in H. influenzae was > 10% in all three studies, with correspondingly high rates of ampicillin resistance. Trimethoprim-sulphamethoxazole was the least active agent tested against H. influenzae, with resistance rates of > 40% recorded in all three studies. All H. influenzae isolates were susceptible to cefuroxime, ceftriaxone, azithromycin and levofloxacin. Of the M. catarrhalis isolates, 98.0% in 1997-1998, 98.0% in 1999-2000 and 81.8% in 2001-2002 were beta-lactamase-positive. The continued high prevalence of antimicrobial resistance in Brazil underscores the importance of current surveillance initiatives. Levofloxacin, a fluoroquinolone prescribed widely for respiratory tract infections, continued to show potent activity against key respiratory pathogens.

Anti-Bacterial Agents↗
PubMed2006

An emerging avian influenza A virus H5N7 is a genetic reassortant of highly pathogenic genes.

We full genome characterised the newly discovered avian influenza virus H5N7 subtype combination isolated from a stock of Danish game ducks to investigate the composition of the genome and possible features of high pathogenicity. It was found that the haemagglutinin and the acidic polymerase genes were closely related to a low pathogenic H5 strain (A/Duck/Denmark/65047/04 H5N2). The neuraminidase and the non-structural genes were closely related to the highly pathogenic H7N7 strains from The Netherlands 2003. The basic polymerase genes 1 and 2 were shared between the Danish H5N7 and H5N2 and the H7N7 from The Netherlands. The nucleoprotein and the matrix genes were closely related to H6 strains. Thus, the new H5N7 subtype share genes with H5, H7 and H6 subtypes and possesses internal genes originating from highly pathogenic strains. The findings emphasize the need for surveillance presumed low pathogenic avian influenza A viruses.

Animals↗
PubMed2022

Pneumococcal within-host diversity during colonization, transmission and treatment.

Characterizing the genetic diversity of pathogens within the host promises to greatly improve surveillance and reconstruction of transmission chains. For bacteria, it also informs our understanding of inter-strain competition and how this shapes the distribution of resistant and sensitive bacteria. Here we study the genetic diversity of Streptococcus pneumoniae within 468 infants and 145 of their mothers by deep sequencing whole pneumococcal populations from 3,761 longitudinal nasopharyngeal samples. We demonstrate that deep sequencing has unsurpassed sensitivity for detecting multiple colonization, doubling the rate at which highly invasive serotype 1 bacteria were detected in carriage compared with gold-standard methods. The greater resolution identified an elevated rate of transmission from mothers to their children in the first year of the child's life. Comprehensive treatment data demonstrated that infants were at an elevated risk of both the acquisition and persistent colonization of a multidrug-resistant bacterium following antimicrobial treatment. Some alleles were enriched after antimicrobial treatment, suggesting that they aided persistence, but generally purifying selection dominated within-host evolution. Rates of co-colonization imply that in the absence of treatment, susceptible lineages outcompeted resistant lineages within the host. These results demonstrate the many benefits of deep sequencing for the genomic surveillance of bacterial pathogens.

Child↗
PubMed2026

Four-year surveillance of major Gram-negative pathogens in a Saudi tertiary hospital: clinical distribution, comorbidity profiles, and antimicrobial resistance.

PURPOSE: To describe four-year diagnostic-distribution, burden, and antimicrobial-resistances of major Enterobacterales and Pseudomonas aeruginosa in a tertiary-care surveillance framework. PATIENTS AND METHODS: We retrospectively studied first non-duplicate-isolate per/patient/organism between 2022-2025 at a Saudi tertiary-care. Diagnostics used automated-platforms with GeneXpert-Carba-R employed parallel to cultures. Susceptibility interpretations used CLSI-breakpoints relevant to test-year. Annual-trends were assessed with grouped-binomial logistic-regression, and Benjamini-Hochberg false-discovery-rate correction was applied within prespecified analysis. RESULTS: Among 1,857 isolates, Klebsiella pneumoniae was most frequent (36.2%), followed by P.&#xa0;aeruginosa (33.4%), Escherichia coli (17.9%), and Enterobacter cloacae (12.3%). Mean patient age was 64.8&#x2009;years, 51.3% isolates were from intensive-care, 37.4% from urine, and 80.8% records had comorbidity. K.&#xa0;pneumoniae showed overall ESBL (76.6%), CRE (59.9%), MDR (69.3%), panel-defined XDR (64.7%), and panel-defined PDR (15.2%) frequencies. Enterobacterales ESBL-positivity increased (58.1% to 76.8%;q&#x2009;<0.001), whereas meropenem non-susceptibility decreased (52.6% to 33.2%;q&#x2009;<0.001). In P.&#xa0;aeruginosa, ceftazidime non-susceptibility increased (55.2% to 78.6%;q&#x2009;<0.001), meropenem decreased (46.8% to 32.9%;q&#x2009;=&#x2009;0.031), and tobramycin increased (22.2% to 45.7%;q&#x2009;=&#x2009;0.030). Crude-comorbidity differences remained insignificant after false-discovery-rate correction. CONCLUSION: We show a persistent species-specific Gram-negative resistance burden, led by K.&#xa0;pneumoniae and accompanied by substantial P.&#xa0;aeruginosa non-susceptibility. This supports organism-specific detections, antibiograms and continued multicenter-surveillance linked to antimicrobial exposure, genomic-data, and patient outcomes.

ESBL↗
PubMed1984

Bacteria associated with crabs from cold waters with emphasis on the occurrence of potential human pathogens.

A diverse array of bacterial species, including several potential human pathogens, was isolated from edible crabs collected in cold waters. Crabs collected near Kodiak Island, Alaska, contained higher levels of bacteria than crabs collected away from regions of human habitation. The bacteria associated with the crabs collected near Kodiak included Yersinia enterocolitica, Klebsiella pneumoniae, and coagulase-negative Staphylococcus species; the pathogenicity of these isolates was demonstrated in mice. Although coliforms were not found, the bacterial species associated with the tissues of crabs collected near Kodiak indicate possible fecal contamination that may have occurred through contact with sewage. Compared with surrounding waters and sediments, the crab tissues contained much higher proportions of gram-positive cocci. As revealed by indirect plate counts and direct scanning electron microscopic observations, muscle and hemolymph tissues contained much lower levels of bacteria than shell and gill tissues. After the death of a crab, however, the numbers of bacteria associated with hemolymph and muscle tissues increased significantly. Microcosm studies showed that certain bacterial populations, e.g., Vibrio cholerae, can be bioaccumulated in crab gill tissues. The results of this study indicate the need for careful review of waste disposal practices where edible crabs may be contaminated with microorganisms that are potential human pathogens and the need for surveillance of shellfish for pathogenic microorganisms that naturally occur in marine ecosystems.

Alaska↗
PubMed2002

Evolving resistance patterns in community-acquired respiratory tract pathogens: first results from the PROTEKT global surveillance study. Prospective Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin.

In recent years, antibacterial resistance among respiratory pathogens implicated in community-acquired respiratory tract infections (RTIs) has spread worldwide at an alarming rate. Thus, there is a pressing need for new antibacterials that retain activity against resistant organisms, have a low potential to select for resistance and do not induce cross-resistance. Telithromycin is the first of a new class of antibacterials - the ketolides - that have been designed specifically to overcome resistance among respiratory tract pathogens. This paper presents the first results of the PROTEKT study (Prospective Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin), a worldwide surveillance study initiated to chart the prevalence of important resistance phenotypes and genotypes and the comparative activity of telithromycin against such strains. Analysis of over 7,000 bacterial isolates by April 2001 has confirmed the notable prevalence of strains resistant to commonly prescribed RTI antibacterials for all the pathogens studied. Telithromycin demonstrates high activity against isolates of Streptococcus pneumoniae, irrespective of penicillin G, macrolide or fluoroquinolone resistance. Telithromycin is also highly active against other respiratory tract pathogens, including Streptococcus pyogenes and beta-lactamase-producing strains of Haemophilus influenzae and Moraxella catarrhalis. These data justify the assertion that telithromycin is a promising new candidate for the empirical treatment of community-acquired RTIs, particularly in the face of increasing antibacterial resistance.

Anti-Bacterial Agents↗