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R Pallares

Publications and source records attributed to R Pallares.

At least 37 records · Page 2Linked to original sources

Resistance to penicillin and cephalosporin and mortality from severe pneumococcal pneumonia in Barcelona, Spain.

BACKGROUND: Penicillin-resistant strains of Streptococcus pneumoniae are now found worldwide, and strains with resistance to cephalosporin are being reported. The appropriate antibiotic therapy for pneumococcal pneumonia due to resistant strains remains controversial. METHODS: To examine the effect of resistance to penicillin and cephalosporin on mortality, we conducted a 10-year, prospective study in Barcelona of 504 adults with culture-proved pneumococcal pneumonia. RESULTS: Among the 504 patients, 145 (29 percent) had penicillin-resistant strains of S. pneumoniae (minimal inhibitory concentration [MIC] of penicillin G, 0.12 to 4.0 micrograms per milliliter), and 31 patients (6 percent) had cephalosporin-resistant strains (MIC of ceftriaxone or cefotaxime, 1.0 to 4.0 micrograms per milliliter). Mortality was 38 percent in patients with penicillin-resistant strains, as compared with 24 percent in patients with penicillin-sensitive strains (P = 0.001). However, after the exclusion of patients with polymicrobial pneumonia and adjustment for other predictors of mortality, the odds ratio for mortality in patients with penicillin-resistant strains was 1.0 (95 percent confidence interval, 0.5 to 1.9; P = 0.84). Among patients treated with penicillin G or ampicillin, the mortality was 25 percent in the 24 with penicillin-resistant strains and 19 percent in the 126 with penicillin-sensitive strains (P = 0.51). Among patients treated with ceftriaxone or cefotaxime, the mortality was 22 percent in the 59 with penicillin-resistant strains and 25 percent in the 127 with penicillin-sensitive strains (P = 0.64) The frequency of resistance to cephalosporin increased from 2 percent in 1984-1988 to 9 percent in 1989-1993 (P = 0.002). Mortality was 26 percent in patients with cephalosporin-resistant S. pneumoniae and 28 percent in patients with susceptible organisms (P = 0.89). Among patients treated with ceftriaxone or cefotaxime, mortality was 22 percent in the 18 with cephalosporin-resistant strains and 24 percent in the 168 with cephalosporin-sensitive organisms (P = 0.64). CONCLUSIONS: Current levels of resistance to penicillin and cephalosporin by S. pneumoniae are not associated with increased mortality in patients with pneumococcal pneumonia. Hence, these antibiotics remain the therapy of choice for this disease.

Adult↗

A single daily dose of ceftriaxone for bacterial meningitis in adults: experience with 84 patients and review of the literature.

Although the pharmacokinetics of ceftriaxone allows its administration in a single daily dose, this practice is not standard in the treatment of bacterial meningitis. Herein, we review our experience and that of other investigators with this mode of therapy. We used a single daily dose of ceftriaxone (50 mg/[kg.d]; maximum, 4 g/d) for the treatment of bacterial meningitis in 84 adult patients. Meningitis was due to Neisseria meningitidis in 34 cases, to Streptococcus pneumoniae in 25, to Escherichia coli in three, to Klebsiella pneumoniae in two, to Haemophilus influenzae in two, to viridans streptococci in two, and to an unknown agent in 16. Eleven patients died, for an overall mortality of 13%; therapy failed in three additional cases. The mean trough levels of ceftriaxone in cerebrospinal fluid was 3.5 micrograms/mL; the median trough bactericidal titer at this site was 1:128. Both our experience and that in the literature suggest that a single daily dose is optimal when ceftriaxone is used for the treatment of bacterial meningitis.

Adolescent↗

Characteristics of and risk factors for relapse of brucellosis in humans.

For 16 years we prospectively observed 530 adult patients with brucellosis to analyze the characteristics of and risk factors for relapse. Clinical and laboratory findings from 86 relapsed patients were milder during the relapse episode when compared with those for the same patients during the initial disease. Blood cultures were positive for Brucella melitensis in 65% of cases during relapse and in approximately 80% of cases during the initial disease. Risk factors that were identified as being independently associated with relapse (by logistic regression analysis) were "less-effective" antibiotic therapy (OR, 8.3; 95% CI, 4.6-15.1), positive blood cultures during initial disease (OR, 2.7; 95% CI, 1.2-6.2), < or = 10-day duration of the disease before treatment (OR, 1.9; 95% CI, 1.1-3.6), male sex (OR, 1.8; 95% CI, 1.02-3.8) and a platelet count of < or = 150 x 10(3)/mm3 (OR, 1.7; 95% CI, 1.1-2.8). These data show that relapse of brucellosis is sometimes difficult to diagnose and that it can be an insidious disease. In addition to inappropriate antibiotic therapy, other factors, such as those indicating a more aggressive disease and/or a deficient immunologic response, seem to play an important role in the relapse of brucellosis.

Adolescent↗

In vitro activities of 22 beta-lactam antibiotics against penicillin-resistant and penicillin-susceptible viridans group streptococci isolated from blood.

A total of 410 strains of viridans group streptococci isolated consecutively from blood were tested by the microdilution method for in vitro susceptibility to 22 beta-lactam antibiotics. One hundred thirty-eight strains (33.6%) were resistant to penicillin with a MIC range of 0.25 to 8 micrograms/ml. MICs of all beta-lactam agents tested were higher for penicillin-resistant strains than for susceptible strains. These antibiotics were classified into three groups according to their in vitro activities (MICs at which 50 and 90% of the isolates are inhibited). Beta-Lactams of the first group (these included imipenem, cefpirome, FK-037, cefditoren, cefotaxime, ceftriaxone, and cefepime) showed activities higher than or similar to that of penicillin against penicillin-resistant viridans group streptococci. However, 80% of highly penicillin-resistant Streptococcus mitis organisms required cefotaxime and ceftriaxone MICs of > or = 2 micrograms/ml (range, 2 to 16 micrograms/ml). Beta-Lactams of the second group (cefpodoxime, ampicillin, amoxicillin-clavulanate, piperacillin, and cefuroxime) showed lower activities than penicillin. Finally, antibiotics of the third group (cephalothin, oxacillin, ceftazidime, cefixime, cefaclor, cefetamet, cefadroxil, cephalexin, and ceftibuten) showed poor in vitro activities. Therefore, some of the beta-lactam agents included in the first group could be an acceptable alternative in the treatment of serious infections due to strains highly resistant to penicillin, although clinical experience is needed.

Anti-Bacterial Agents↗

Relationship between quinolone use and emergence of ciprofloxacin-resistant Escherichia coli in bloodstream infections.

From 1988 to 1992, 27 of 855 cases of Escherichia coli bacteremia in nonneutropenic adult patients observed at our hospital were due to ciprofloxacin-resistant (CIPRO-R) strains. Eighteen episodes (67%) were community acquired, and nine (33%) were nosocomially acquired. Overall, the rates of E. coli bacteremia caused by CIPRO-R strains increased steadily from 0% in 1988 to 7.5% in 1992 (P < 0.01). There was a statistically significant correlation between the incidence of CIPRO-R E. coli bacteremia and the upward trend in fluoroquinolone (norfloxacin and ciprofloxacin) use in the community (r = 0.974; P = 0.005) as well as in the hospital (r = 0.975; P = 0.005). When we compared the 27 case patients with 54 simultaneous control patients who had ciprofloxacin-susceptible E. coli bacteremia, the case patients more frequently had chronic underlying diseases (71 versus 37%; P = 0.004), urinary tract infection (74 versus 50%; P = 0.03), prior surgery (22 versus 6%; P = 0.02), and prior fluoroquinolone use (63 versus 4%; P < 0.001). A logistic regression analysis identified prior quinolone use as the only independent risk factor for CIPRO-R E. coli bacteremia. In conclusion, our study shows a significant correlation between ciprofloxacin resistance and fluoroquinolone use and indicates that prior fluoroquinolone use seems to be the most important risk factor for CIPRO-R E. coli bacteremia.

Adult↗

Risk factors for nosocomial bacteremia due to methicillin-resistant Staphylococcus aureus.

In a prospective surveillance study (February 1990-December 1991) performed at a 1000-bed teaching hospital to identify risk factors for nosocomial methicillin-resistant Staphylococcus aureus (MRSA) bacteremia, 309 patients were found to be colonized (n = 103; 33%) or infected (n = 206; 67%) by MRSA. Sixty-three of them developed bacteremia. Compared with 114 patients who had nosocomial bacteremia caused by methicillin-sensitive Staphylococcus aureus during the same period of time, MRSA bacteremic patients had more severe underlying diseases (p < 0.01), were more often in intensive care units (p < 0.01) and had received prior antibiotic therapy more frequently (p < 0.01). To further identify risk factors for MRSA bacteremia, univariate and multivariate analyses of this series of 309 patients were performed using the occurrence of MRSA bacteremia as the dependent variable. Among 14 variables analyzed, intravascular catheterization, defined as one or more intravascular catheters in place for more than 48 h, was the only variable selected by a logistic regression model as an independent risk factor (OR = 2.7, CI = 1.1-6.6). The results of this study reinforce the concept that recent antibiotic therapy may predispose patients to MRSA infection and suggest that among patients colonized or infected by MRSA, those with intravascular catheters are at high risk of developing MRSA bacteremia.

Adult↗

Risk factors for nosocomial Legionella pneumophila pneumonia.

Over a 5-yr period, from January 1985 to January 1990, we prospectively studied 300 episodes of nosocomial pneumonia in a 1,000-bed teaching hospital. All cases had an accurate bacteriologic diagnosis obtained by means of highly reliable techniques. Legionella pneumophila caused a total of 36 episodes; 22 were endemic and 14 occurred during an epidemic outbreak. No patient with Legionella pneumonia had been intubated before infection. To identify risk factors for nosocomial L. pneumophila pneumonia, we compared the 22 endemic cases of nosocomial pneumonia due to L. pneumophila with the 264 cases due to other bacteria. After adjusting for other variables by means of logistic regression analysis, cytotoxic chemotherapy (OR = 5.2; 95% CI, 1.5 to 17.9) and use of corticosteroids (OR = 4.6; 95% CI, 1.5 to 14.1) were positively associated with L. pneumophila pneumonia, whereas previous antibiotic therapy (OR = 0.2; 95% CI, 0.1 to 0.8) and lowered consciousness (OR = 0.2; 95% CI, 0.07 to 0.8) were negatively associated. The major risk factors for Legionella pneumonia delineated in this study should be considered in the clinical approach to and empiric therapy of patients with suspected nosocomial pneumonia.

Adrenal Cortex Hormones↗

Cephalosporins as risk factor for nosocomial Enterococcus faecalis bacteremia. A matched case-control study.

BACKGROUND: Nosocomial enterococcal infections have increased in various institutions, and patients with these infections had often been treated with cephalosporins during the previous weeks. The objective of this study was to determine whether the use of second- and third-generation cephalosporins is a risk factor for nosocomial enterococcal bacteremia (NEB), by means of a matched case-control study design. METHODS: Two hundred seven cases of NEB were studied. A control was matched to each case by sex, age (+/- 10 years), date of admission (+/- 2 years), hospital service, days of hospitalization, primary diagnosis, and operative procedures. RESULTS: One hundred fifty-six cases had an appropriate matched control. The univariate analysis of unmatched variables showed that the presence of a urinary catheter (odds ratio [OR], 3.8), mechanical ventilation (OR = 2.6), and cephalosporin use (OR = 5.1) were associated with NEB. Using a conditional logistic regression model, cephalosporin use (adjusted OR = 4.8, 95% confidence interval, 2.3 to 9.8) and urinary catheter use (adjusted OR = 3.6, 95% confidence interval, 1.7 to 7.4) remained significantly associated with NEB after controlling for other unmatched variables. CONCLUSIONS: These data show that the use of second- and third-generation cephalosporins may be a major risk factor for NEB. It may explain, at least partially, the steadily increasing number of enterococcal infections observed in some hospitals.

Adult↗

Secular trends in rates and etiology of nosocomial urinary tract infections at a university hospital.

To examine changing trends in the microbial etiology of nosocomial urinary tract infections, we reviewed culture data from a surveillance database for the calendar years 1982 to 1991. The overall rates of nosocomial urinary tract infections have increased significantly during the last decade from 2.63 per 1,000 patient-days to 4.35 per 1,000 patient-days (p = 0.0023). For specific isolates the rates of yeasts, Klebsiella pneumoniae and group B streptococcus have increased significantly during the last decade. The rates of Escherichia coli, Proteus species and Pseudomonas species have all decreased. Analysis of these secular trends can provide important information relating to the etiology of nosocomial urinary tract infections. It is likely that antibiotic "pressure" has influenced the microbiology of infections and that altered case-mix would explain much of the increase in rates. However, the multiple reasons for these secular trends and their precise contributions to them are unknown.

Bacteria↗

Trends in antimicrobial utilization at a tertiary teaching hospital during a 15-year period (1978-1992).

BACKGROUND: Antimicrobials are a major part of hospital pharmacy budgets and must be considered in resource planning and spending projections. Logically, trends in antimicrobial usage should be linked to trends in resistant pathogens. OBJECTIVE: To examine long-term trends in antimicrobial use over a 15-year period (1978 to 1992) and contrast them with changes in pathogens causing nosocomial bacteremia. SETTING: A 900-bed, tertiary care teaching hospital. METHODS: Pharmacy records were reviewed to identify parenteral antimicrobial agents administered to adult inpatients. Results were expressed in average daily adult doses per 1,000 patient days. RESULTS: Chloramphenicol use decreased, while use of penicillin G, antistaphylococcal penicillins, first-generation cephalosporins, and aminoglycosides remained relatively stable. In contrast, there was a sharp increase in the use of second- and third-generation cephalosporins (7-fold and 6.5-fold increase, respectively), vancomycin (161-fold increase), metronidazole (32-fold increase) and amphotericin B (35-fold increase). The proportion of nosocomial bacteremias due to methicillin-resistant gram-positive bacteria rose, but gentamicin resistance in gram-negatives remained at low levels. During the past 14 years, the percentage of patients receiving at least one parenteral antimicrobial rose from 23% to 44%. Among patients receiving antimicrobials, the average number of different agents used per patient increased from 1.8 to 2.1. CONCLUSIONS: If newer agents were available, use of older agents usually declined. If newer alternatives were not available, use of older agents rose sharply. The increased use of antimicrobials in adults was related to the expanded proportion of patients receiving these agents.

Adult↗

Treatment of human brucellosis with doxycycline plus rifampin or doxycycline plus streptomycin. A randomized, double-blind study.

OBJECTIVE: To compare the effectiveness of doxycycline-rifampin (DR) combination therapy with that of the classic doxycycline-streptomycin (DS) combination in patients with brucellosis. DESIGN: A randomized, double-blind study, with a mean follow-up of 15.7 months. SETTING: A 1000-bed teaching hospital in Barcelona, Spain. PATIENTS: Ninety-five patients (68 men and 27 women; mean age, 39 years) diagnosed with brucellosis on the basis of both clinical and serologic findings; 81 of these patients had blood cultures positive for Brucella melitensis. INTERVENTIONS: Forty-four patients received doxycycline, 100 mg every 12 hours, and rifampin, 15 mg/kg body weight per day in a single morning dose, for 45 days; 51 patients received the same dose of doxycycline for 45 days plus streptomycin, 1 g/d for 15 days. MAIN OUTCOME MEASURES: Therapeutic failure and relapse during the follow-up period. RESULTS: The mean time to defervescence was 4.2 days for the DR group and 3.2 days for the DS group (P greater than 0.2). The actuarial probability of therapeutic failure or relapse at 12 months of follow-up (Kaplan-Meier) was 14.4% in the DR group and 5.9% in the DS group (difference, 8.5%; 95% Cl, -4.8% to 21.6%; P greater than 0.2). All three patients with spondylitis in the DR group failed therapy compared with one of four patients in the DS group. Excluding patients with spondylitis, the actuarial failure rate was 4.9% and 4.3% in the DR and DS groups, respectively, at 12 months of follow-up (difference, 0.6%; Cl, -8.1% to 9.4%; P greater than 0.2). CONCLUSIONS: Doxycycline-rifampin combination therapy for 45 days is as effective as the classic DS combination in most patients with brucellosis; however, DR therapy might be less effective in those patients with spondylitis.

Adolescent↗

Trends in antimicrobial resistance of clinical isolates of Streptococcus pneumoniae in Bellvitge Hospital, Barcelona, Spain (1979-1990).

From January 1979 to December 1990 we studied the susceptibility of 1,492 pneumococcal strains isolated from adult patients in Bellvitge Hospital, Barcelona, Spain, to nine antimicrobial agents. Among clinically significant pneumococci, the incidence of penicillin-resistant strains increased from 4.3% in 1979 to 40% in 1990, and that of erythromycin-resistant strains also rose from 0% in 1979 to 9.4% in 1990. On the other hand, the incidence of strains resistant to tetracycline decreased from 76.1% to 37.6%, as did that of chloramphenicol-resistant strains, from 56.5% to 29.4%. The incidence of co-trimoxazole-resistant strains was about 40% throughout the study. Even more alarming was the finding that about 70% of penicillin-resistant strains showed multiple resistance to non-beta-lactam antibiotics. All pneumococci were susceptible to vancomycin, and all but six were susceptible to rifampin. We observed that isolates from cerebrospinal fluid and the respiratory tract were significantly more resistant to penicillin than were isolates from blood. The majority of strains (95%) belonged to serogroups or serotypes included in the 23-valent pneumococcal vaccine and 77.6% of penicillin-resistant strains belonged to groups 23, 6, 9, and 19.

Adult↗

Clindamycin vs penicillin for anaerobic lung infections. High rate of penicillin failures associated with penicillin-resistant Bacteroides melaninogenicus.

Thirty-seven adult patients with anaerobic lung infections (27 lung abscesses and 10 necrotizing pneumonias) were submitted to transthoracic needle-aspiration and/or bronchoscopic specimen brush cultures before therapy and thereafter in all cases considered to be failures. Patients were randomly assigned to receive either clindamycin, 600 mg intravenously every 6 hours, or penicillin G, 2 million U every 4 hours for no less than 8 days, until clinical and radiological improvement became apparent. Treatment was continued orally with clindamycin, 300 mg every 6 hours, or penicillin V, 750 mg every 6 hours, until completing a minimum of 4 weeks. Ten of the 47 anaerobes initially isolated from the lung (nine Bacteroides melaninogenicus and one Bacteroides capillosus) were resistant to penicillin, but none were resistant to clindamycin. Five of the nine patients harboring these penicillin-resistant Bacteroides received penicillin, and all failed to respond to therapy. Overall, eight of the 18 patients in the penicillin group and one of 19 in the clindamycin group failed to respond to therapy. These drugs were equally well tolerated in both groups. The presence of penicillin-resistant Bacteroides is a frequent cause of penicillin failure in patients with anaerobic lung infections. In this setting, clindamycin appears to be the current therapy of choice for initial treatment.

Adult↗

Intravenous ciprofloxacin therapy in severe infections.

Fifty evaluable patients (34 men and 16 women; mean age, 47 years) with severe infections were given intravenous ciprofloxacin (200 mg every 12 hours) for a mean of 14 days. Therapy was continued with oral ciprofloxacin 500 to 750 mg every 12 hours in 34 cases for a mean of 57 days. The sources of the infections were bone and joint (26 patients), respiratory tract (10 patients), urinary tract (four patients), soft tissue (four patients), abdominal (three patients), bacteremia of unknown origin (two patients), and right-sided endocarditis (one patient). Fifteen patients (30 percent) were bacteremic. Causative organisms included Pseudomonas aeruginosa (32 patients), other gram-negative bacilli (18 patients), and gram-positive cocci (nine patients). Minimal inhibitory concentrations ranged between 0.03 and 1 microgram/ml. Mean peak serum concentrations were 1.58 micrograms/ml (intravenous) and 2 micrograms/ml (oral); mean trough serum concentrations were 0.23 micrograms/ml (intravenous) and 0.32 micrograms/ml (oral). Serum bactericidal activity values achieved after intravenous and oral therapy were similar. Response to therapy was evaluated separately in patients with or without osteomyelitis. In 30 patients with infections other than osteomyelitis, clinical cure was achieved in 27 (90 percent), and therapy failure occurred in three patients. In the 20 remaining patients with osteomyelitis, 15 (75 percent) had a satisfactory response, with apparent cure after a mean follow-up of 11 months, whereas five had therapeutical failure (P. aeruginosa became resistant in four of them). Overall, no major adverse effects were encountered. Superinfection by a resistant P. aeruginosa was observed in three patients. Intravenous ciprofloxacin is an effective and safe agent for the therapy of severe infections caused by susceptible organisms.

Adolescent↗

Characteristics and antibiotic therapy of adult meningitis due to penicillin-resistant pneumococci.

Of 66 episodes of pneumococcal meningitis seen in Bellvitge Hospital, Barcelona, Spain (January 1981 to June 1987), 15 (23 percent) were due to penicillin-resistant pneumococci [minimal inhibitory concentrations (MICs) of 0.1 to 4 micrograms/ml]. Fifty percent of these strains were also resistant to chloramphenicol. Most were sporadic community-acquired cases. Clinical characteristics were similar in both penicillin-resistant and penicillin-sensitive cases. Those cases with MICs of greater than 1 microgram/ml did not show a response to penicillin therapy. Of nine patients treated with cefotaxime (200 to 350 mg/kg per day) with penicillin G MICs of 0.1 to 4 micrograms/ml and cefotaxime MICs of less than or equal to 0.03 to 1 microgram/ml, seven recovered, one experienced a relapse after 14 days of therapy and the infection was cured with intravenous vancomycin, and one patient died with sterile cerebrospinal fluid. Thus, adults with meningitis due to penicillin-resistant pneumococci may be adequately treated with high doses (around 300 mg/kg per day) of intravenous cefotaxime if MICs of penicillin G are less than or equal to 4 micrograms/ml. Cases with higher resistance may require another antibiotic such as vancomycin.

Adult↗

Specific antibodies detected during relapse of human brucellosis.

We studied 10 patients who had a relapse of brucellosis for significant serological changes during relapse. By the Coombs test, the pre-relapse and post-relapse median (range) titers of antibody to Brucella were 1:1120 (1:40-1:10,240) and 1:10,240 (1:40-1:81,920), respectively (P = .0069); by enzyme-linked immunosorbent assay (ELISA) for IgG, these values were 1:2240 (1:60-1:10,240) and 1:10,240 (1:160-1:81,920; P = .0069); by ELISA for IgA, the median titer increased 3.36 times but did not reach statistical significance (P = .0929); by tube agglutination, dithiothreitol (DTT) agglutination, and ELISA for IgM, median titers did not change. Nine patients had a significant titer increase by Coombs test and IgG ELISA, three had a significant increase by tube and DTT agglutination, none had significant increases by IgM ELISA, and one had no significant increase after relapse. Our findings show that for most patients with a relapse of brucellosis, there is an increase in IgG titers, as detected by ELISA and Coombs test, but no change in IgM titers.

Adolescent↗

Risk factors and response to antibiotic therapy in adults with bacteremic pneumonia caused by penicillin-resistant pneumococci.

We retrospectively studied 24 adults with bacteremic pneumonia (25 episodes) due to penicillin-resistant pneumococci, for which the minimal inhibitory concentrations (MICs) of penicillin G were 0.12 to 8.0 micrograms per milliliter; 79 percent of the strains showed multiple antibiotic resistance. As compared with 48 control patients with bacteremic pneumonia caused by penicillin-sensitive pneumococci, the 24 patients with penicillin-resistant pneumococci had a significantly higher incidence of use of beta-lactam antibiotics during the previous three months (65 vs. 17 percent, P = 0.0008), hospitalization during the previous three months (58 vs. 21 percent, P = 0.0038), nosocomial pneumonia (37 vs. 6 percent, P = 0.0032), episodes of pneumonia during the previous year (29 vs. 4 percent, P = 0.010), and factors on initial presentation that were associated with a poor prognosis (an initially critical condition) (67 vs. 27 percent, P = 0.0030). Their overall mortality rate was significantly higher (54 vs. 25 percent, P = 0.0298). Eleven of 19 episodes of pneumonia due to organisms for which MICs were 0.12 to 2.0 micrograms per milliliter, which were treated with penicillin G (10 episodes) or another beta-lactam agent (9 episodes), resulted in recovery (2 of 10 patients in an initially critical condition recovered, as compared with all of 9 not initially in a critical condition, P = 0.0012). Two patients who had penicillin-resistant pneumococci for which MICs were 4.0 and 8.0 micrograms per milliliter did not respond to ampicillin and ticarcillin therapy, respectively. Our study suggests that pneumonia due to penicillin-resistant pneumococci may occur more often in a population with some identifiable risk factors, and may respond to intravenous high-dose penicillin therapy if MICs are less than or equal to 2 micrograms per milliliter. Cases involving higher resistance may require an alternative antibiotic.

Anti-Bacterial Agents↗