sultamicillin and Escherichia-coli-Infections

In a prospective study 105 children hospitalized with soft tissue infection, 11 children with suppurative arthritis and 9 children with osteomyelitis were treated with either parenterally administered ampicillin/sulbactam or ceftriaxone. Treatment was randomized using a computer-generated table in a 2:1 fashion: 84 patients received ampicillin/sulbactam and 41 patients received ceftriaxone. Organisms isolated from wound site or blood cultures included Staphylococcus aureus (33), Streptococcus pyogenes (19), Haemophilus influenzae (9) including 4 beta-lactamase-positive organisms, Streptococcus pneumoniae (5), Neisseria gonorrhoeae (3) and 9 other organisms. Clinical and bacteriologic response was satisfactory in 100% of the ampicillin/sulbactam-treated patients and in 93% of the ceftriaxone-treated patients. Two patients with S. aureus infections treated with ceftriaxone had a delayed response and required change in therapy to parenterally administered oxacillin. Ampicillin/sulbactam represents a potentially useful single agent for the treatment of cellulitis and bone or joint infections in pediatric patients.

Topics: Acinetobacter Infections; Adolescent; Ampicillin; Arthritis, Infectious; Ceftriaxone; Cellulitis; Child; Child, Preschool; Drug Therapy, Combination; Escherichia coli Infections; Female; Gonorrhea; Haemophilus Infections; Humans; Infant; Male; Osteomyelitis; Prospective Studies; Random Allocation; Staphylococcal Infections; Streptococcal Infections; Sulbactam

This study aimed to compare treatment outcomes for bloodstream infections (BSI) caused by a piperacillin/tazobactam (PIP/TAZ)-susceptible E. coli among three patient groups: BSI caused by ampicillin/sulbactam (AMP/SLB)-resistant isolates treated with PIP/TAZ, BSI caused by AMP/SLB-sensitive isolates treated with PIP/TAZ, and BSI caused by AMP/SLB-resistant isolates treated with another monotherapy.. This retrospective study was conducted in two academic centres in Europe. Adult patients with E. coli BSI were screened from 2014 to 2020. Inclusion criteria were non-ESBL BSI and initial monotherapy for ≥ 72 h. To reduce the expected bias between the patient groups, propensity score matching was performed. The primary outcome was early treatment response after 72 h and required absence of SOFA score increase in ICU/IMC patients, as well as resolution of fever, leukocytosis, and bacteraemia.. Of the 1707 patients screened, 315 (18.5%) were included in the final analysis. Urinary tract infection was the most common source of BSI (54.9%). Monotherapies other than PIP/TAZ were cephalosporins (48.6%), carbapenems (34.3%), and quinolones (17.1%). Enhanced early treatment response rate was detected (p = 0.04) in patients with BSI caused by AMP/SLB-resistant isolates treated with another monotherapy (74.3%) compared to those treated with PIP/TAZ (57.1%), and was mainly driven by the use of cephalosporins and quinolones (p ≤ 0.03). Clinical success, 28-day mortality, and rate of relapsing BSI did not significantly differ between the groups.. Our study suggests that initial use of PIP/TAZ may be associated with reduced early treatment response in E. coli BSI caused by AMP/SLB-resistant isolates compared to alternative monotherapies.

Topics: Adult; Ampicillin; Anti-Bacterial Agents; Bacteremia; Cephalosporins; Cohort Studies; Escherichia coli; Escherichia coli Infections; Humans; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Quinolones; Retrospective Studies; Sulbactam

The coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide. Bacterial co-infections are associated with unfavourable outcomes in respiratory viral infections; however, microbiological and antibiotic data related to COVID-19 are sparse. Adequate use of antibiotics in line with antibiotic stewardship (ABS) principles is warranted during the pandemic. We performed a retrospective study of clinical and microbiological characteristics of 140 COVID-19 patients admitted between February and April 2020 to a German University hospital, with a focus on bacterial co-infections and antimicrobial therapy. The final date of follow-up was 6 May 2020. Clinical data of 140 COVID-19 patients were recorded: The median age was 63.5 (range 17-99) years; 64% were males. According to the implemented local ABS guidelines, the most commonly used antibiotic regimen was ampicillin/sulbactam (41.5%) with a median duration of 6 (range 1-13) days. Urinary antigen tests for Legionella pneumophila and Streptococcus peumoniae were negative in all cases. In critically ill patients admitted to intensive care units (n = 50), co-infections with Enterobacterales (34.0%) and Aspergillus fumigatus (18.0%) were detected. Blood cultures collected at admission showed a diagnostic yield of 4.2%. Bacterial and fungal co-infections are rare in COVID-19 patients and are mainly prevalent in critically ill patients. Further studies are needed to assess the impact of antimicrobial therapy on therapeutic outcome in COVID-19 patients to prevent antimicrobial overuse. ABS guidelines could help in optimising the management of COVID-19. Investigation of microbial patterns of infectious complications in critically ill COVID-19 patients is also required.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Ampicillin; Anti-Bacterial Agents; Antifungal Agents; Antimicrobial Stewardship; Aspergillosis; Azithromycin; Bacterial Infections; Cohort Studies; Coinfection; COVID-19; Enterobacteriaceae Infections; Escherichia coli Infections; Female; Germany; Humans; Klebsiella Infections; Linezolid; Male; Meropenem; Middle Aged; Piperacillin, Tazobactam Drug Combination; Practice Patterns, Physicians'; Retrospective Studies; SARS-CoV-2; Staphylococcal Infections; Streptococcal Infections; Sulbactam; Vancomycin; Young Adult

Early detection of the site of infection non-invasively with radiolabeled molecules is important for the success of treatment. Technetium-99m labeled antibiotics have the potential to discriminate between bacterial infection and sterile inflammation. Sultamicillin is the tosylate salt of the double ester of sulbactam plus ampicillin. In this study, sultamicillin was labeled with

Topics: Ampicillin; Anti-Bacterial Agents; Escherichia coli; Escherichia coli Infections; Staphylococcal Infections; Staphylococcus aureus; Sulbactam; Technetium; Tin Compounds

Perioperative antibiotic prophylaxis (PAP) is an integral part of kidney transplantation to prevent surgical site infections (SSI). In July 2015, we changed our standard from a multiple-dose to a single-dose (SD) prophylaxis. Here, we report on results with both regimens and a related survey among Eurotransplant renal transplantation centers.. From July 2015, all kidney graft recipients of our center were scheduled to receive SD i.v. cefazolin (group SD, n = 107). They were compared to patients, transplanted since January 2014, receiving our previous standard (i.v. piperacillin/flucloxacillin) until postoperative day (POD) 7, plus oral sultamicillin until POD 10 (group MD, n = 105). The primary endpoint was the number of SSIs during a 3-month observational period.. The frequency of SSI episodes was generally low (group SD vs. MD: 2 vs. 4, p = 0.40). Of note, urinary tract infections occurred in 40 SD vs. 36 MD patients, respectively (p = 0.60). Urinary tract infections were caused by Escherichia coli in 36.8%. Female gender was the only independent risk factor on multivariate analysis (p = 0.002). In addition, 12 episodes of urosepsis in both groups occurred. All-cause infection with multi-resistant bacteria occurred less frequently in SD vs. MD patients (3.7% vs. 8.6%, p = 0.16). A majority of Eurotransplant centers used i.v. single-dose cephalosporins (36.9%), although substances and duration varied remarkably.. Single-dose cefazolin was equally effective and less expensive compared to our previous MD regimen. Based on these findings, we conclude that future prospective studies should be designed to confirm the non-inferiority of single-dose antibiotic regimens.

Topics: Adult; Aged; Ampicillin; Anti-Bacterial Agents; Antibiotic Prophylaxis; Cefazolin; Escherichia coli Infections; Europe; Female; Floxacillin; Humans; Kidney Transplantation; Male; Middle Aged; Perioperative Care; Piperacillin; Postoperative Complications; Retrospective Studies; Sepsis; Sex Factors; Sulbactam; Surgical Wound Infection; Surveys and Questionnaires; Urinary Tract Infections

Empirical and prolonged antimicrobial treatment of urinary tract infections caused by Escherichia coli is associated with the emergence of bacterial resistance, and not all countries have strict policies against the indiscriminate use of drugs in order to prevent resistance. This cross-sectional and retrospective study (2010-2015) aimed to evaluate the sensitivity and resistance of patient-derived E. coli to different drugs broadly used to treat urinary infections in Brazil: ampicillin + sulbactam, cephalothin, ciprofloxacin, norfloxacin, and nitrofurantoin. We obtained 1654 E. coli samples from ambulatory patients with disease symptoms of the urinary tract from a Brazilian public hospital. While all antibiotics were effective in killing E. coli to a large degree, nitrofurantoin was the most effective, with fewer samples exhibiting antibiotic resistance. We assessed the costs of generic and brand name versions of each antibiotic. Nitrofurantoin, the most effective antibiotic, was the cheapest, followed by the fluoroquinolones (ciprofloxacin and norfloxacin), ampicillin + sulbactam and, lastly, cephalothin. Finally, assessment of antibiotic resistance to fluoroquinolones over the study period and extrapolation of the data led to the conclusion that these antibiotics could no longer be effective against E. coli-based urinary infections in approximately 20 years if their indiscriminate use in empirical treatment continues.

Topics: Ampicillin; Anti-Bacterial Agents; Brazil; Ciprofloxacin; Cross-Sectional Studies; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Fluoroquinolones; Humans; Microbial Sensitivity Tests; Nitrofurantoin; Retrospective Studies; Sulbactam; Urinary Tract Infections

Determination of treatment protocols for infections according to antimicrobial susceptibility test (AST) results is are important for controlling the problem of antibiotic resistance. Two standards are widely used in the world. One of them is Clinical Laboratory Standards Institute (CLSI) standards used in Turkey for many years and the other is the European Committee on Antimicrobial Susceptibility Testing (EUCAST) standards which is used in European Union member countries and came into use in 2015 in Turkey. Since the EUCAST standards had higher clinical sensitivity limits particularly for gram-negative bacilli compared to CLSI (2009) standards, there will be some changes in antibiotic resistance profiles of Turkey with the use of EUCAST. CLSI has changed zone diameters after 2009 versions and the differences between the two standards were brought to a minimum level. Knowledge of local epidemiological data is important to determine empirical therapy which will be used in urinary tract infections (UTI). The aim of this study was to determine the differences of antibiotic susceptibility zone diameters based on our local epidemiological data among uropathogenic Escherichia coli isolates according to EUCAST 2014 and CLSI 2014 standards. A total of 298 E.coli strains isolated from urine samples as the cause of uncomplicated acute UTI agents, were included in the study. Isolates were identified by conventional methods and with BBL Crystal E/NF ID System (Becton Dickinson, USA). AST was performed with Kirby Bauer disk diffusion method and results were evaluated and interpreted according to the CLSI 2014 and EUCAST 2014 standards. According to the results, susceptibility rates of isolates against amikacin (100%) and trimethoprim-sulfamethoxazole (63.09%) were identical in both standards. However, statistically significant differences were observed between CLSI and EUCAST standards in terms of susceptibilities against gentamicin (91.95% and 84.56%, respectively; p= 0.004), cefuroxime axetil (20.13% and 77.18%, respectively; p= 0.000) and levofloxacin (73.83% and 67.11%, respectively; p= 0.044). No statistically differences between two standards for ampicillin (32.89% and 36.24%, respectively; p= 0.219), ampicillin-sulbactam (65.77% and 69.13%, respectively; p= 0.216), ciprofloxacin (72.48% and 71.14%, respectively; p= 0.392) and imipenem (94.63% and 95.30%, respectively; p= 0.426) were determined. In this transitional period, continuity of cooperation between the

Topics: Amikacin; Ampicillin; Anti-Bacterial Agents; Bacteriuria; Cefuroxime; Ciprofloxacin; Disk Diffusion Antimicrobial Tests; Drug Resistance, Bacterial; Escherichia coli Infections; European Union; Gentamicins; Humans; Imipenem; Levofloxacin; Microbial Sensitivity Tests; Reference Standards; Sulbactam; Trimethoprim, Sulfamethoxazole Drug Combination; Turkey; Urinary Tract Infections; Uropathogenic Escherichia coli

Ampicillin-sulbactam (A/S) and amoxicillin-clavulanic acid (AUG) are thought to be equally efficacious clinically against the Enterobacteriaceae family. In this study, the in vitro activities of the A/S and AUG were evaluated and compared against Escherichia coli and Klebsiella spp. Antimicrobial susceptibility tests were performed by standard agar dilution and disc diffusion techniques according to the Clinical and Laboratory Standards Institute (CLSI). During the study period, 973 strains were isolated. Of the 973 bacteria isolated, 823 were E. coli and 150 Klebsiella spp. More organisms were found to be susceptible to AUG than A/S, regardless of the susceptibility testing methodology. The agar dilution results of the isolates that were found to be sensitive or resistant were also compatible with the disc diffusion results. However, some differences were seen in the agar dilution results of some isolates that were found to be intermediately resistant with disc diffusion. In E. coli isolates, 17 of the 76 AUG intermediately resistant isolates (by disc diffusion), and 17 of the 63 A/S intermediately resistant isolates (by disc diffusion) showed different resistant patterns by agar dilution. When the CLSI breakpoint criteria are applied it should be considered that AUG and A/S sensitivity in E. coli and Klebsiella spp. strains may show differences.

Topics: Amoxicillin-Potassium Clavulanate Combination; Ampicillin; Colony Count, Microbial; Diffusion Chambers, Culture; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae Infections; Escherichia coli; Escherichia coli Infections; Humans; Klebsiella; Sulbactam

The purpose of this study was to determine whether early antibiotic administration to pregnant rabbits with intrauterine infection could prevent preterm delivery and perinatal mortality.. Under hysteroscopic guidance, pregnant rabbits at 70% gestation (21 days) were allocated to three groups: (1) control group, transcervical inoculation of 0.2 ml phosphate-buffered saline (n = 16); (2) infection group, transcervical inoculation of 0.2 ml of 10(5) colony-forming units (CFU) of Escherichia coli (n = 21); (3) infection and antibiotics group, transcervical inoculations of 0.2 ml of 10(5) CFU of E. coli and ampicillin-sulbactam 150 mg/kg every 8 h intramuscularly (n = 32). To examine the consequences of treatment delay, animals in the latter group were subdivided to receive antibiotics at different time intervals of 0, 6, 11 and 18 h after bacterial inoculation. The intervals from bacterial inoculation to delivery and litter survival were documented. Systemic (rectal) temperatures were recorded at 4 h intervals through the first 36 h and every 12 h until delivery. A p value of < 0.05 was considered significant.. All rabbits inoculated with E. coli without antibiotic treatment delivered prematurely. The median inoculation-to-delivery interval was significantly shorter in the infected group than in the control group (median 32 h, range 14.9-76.5 h vs. median 219 h, range 173-246 h, respectively; p < 0.0001). Antibiotic administration within 12 h of inoculation, but not after 18 h, increased duration of pregnancy (by reducing the rate of preterm delivery) and neonatal survival (0% vs. 71%; p < 0.0001). The mean temperatures at delivery of animals whose treatments began at 6 and 11 h post-inoculation were significantly lower than those untreated with antibiotics or those treated at 18 h post-inoculation (p < 0.0001 for each comparison).. Antibiotic administration can prolong pregnancy and reduce perinatal mortality if administered early (within 12 h of microbial inoculation) in a rabbit model of ascending intrauterine infection.

Topics: Ampicillin; Animals; Body Temperature; Disease Models, Animal; Drug Therapy, Combination; Escherichia coli Infections; Female; Fetal Membranes, Premature Rupture; Injections, Intramuscular; Pregnancy; Pregnancy Complications, Infectious; Rabbits; Random Allocation; Sulbactam

In a pregnant rabbit model using intracervical inoculation of Escherichia coli with delayed antibiotic therapy, we investigated the rate of positive cultures and histologic inflammation of maternal and fetal compartments and the concentration of tumor necrosis factor-alpha in the amniotic fluid for up to 5 days.. New Zealand White rabbits at 70% gestation were inoculated intracervically with 10(3) - 10(4) colony-forming units of E coli per uterine horn. At varying intervals after inoculation (0.5 - 4.0 hours), antibiotic therapy was initiated with ampicillin-sulbactam. Primary outcomes were positive cultures and histologic inflammation score. Tumor necrosis factor-alpha levels in the amniotic fluid were determined by bioassay.. A total of 60 animals were inoculated with E coli. At the endpoint, uterine cultures were positive more commonly than in the fetus or amniotic fluid (41.8% vs 27.5% vs 17.3%, respectively), which was consistent with an ascending pathway of infection. Inflammation scores were similar in uterus and placenta but lower in fetal lung and absent in fetal brain (2.8 vs 3.1 vs 0.84 vs 0.0, respectively). Comparing the durations of delay in antibiotic administration, we found a significant increase in positive uterine cultures and a significant increase in histologic inflammation score with increasing delay. The proportion of dead pups within a litter was significantly associated with the log of the tumor necrosis factor-alpha concentration in amniotic fluid and the degree of histologic inflammation in the uterus, but not with amniotic fluid or other culture positivity.. The administration of therapeutic doses of antibiotic does not consistently eradicate bacteria from the rabbit uterus nor, more importantly, from the fetus and the amniotic fluid. Obtaining a negative amniotic fluid culture does not exclude either infection in the decidua or the fetus or histologic inflammation with tumor necrosis factor-alpha elaboration.

Topics: Amniotic Fluid; Ampicillin; Animals; Chronic Disease; Drug Administration Schedule; Drug Therapy, Combination; Escherichia coli; Escherichia coli Infections; Female; Fetal Death; Fetal Diseases; Fetus; Inflammation; Pregnancy; Pregnancy Complications, Infectious; Rabbits; Sulbactam; Treatment Failure; Uterine Diseases; Uterus

The incidence of extended-spectrum beta-lactamase (ESbetaL)-mediated resistance has increased markedly during the past decade. Risk factors for colonization with ESbetaL-producing Escherichia coli and Klebsiella species (ESbetaL-EK) remain unclear, as do methods to control their further emergence.. Case-control study.. Two hospitals within a large academic health system: a 725-bed academic tertiary-care medical center and a 344-bed urban community hospital.. Thirteen patients with ESbetaL-EK fecal colonization were compared with 46 randomly selected noncolonized controls.. Duration of hospitalization was the only independent risk factor for ESbetaL-EK colonization (odds ratio, 1.11; 95% confidence interval, 1.02 to 1.21). Of note, 8 (62%) of the patients had been admitted from another healthcare facility. In addition, there was evidence for dissemination of a single K oxytoca clone. Finally, the prevalence of ESbetaL-EK colonization decreased from 7.9% to 5.7% following restriction of third-generation cephalosporins (P = .51).. ESbetaL-EK colonization was associated only with duration of hospitalization and there was no significant reduction following antimicrobial formulary interventions. The evidence for nosocomial spread and the high percentage of patients with ESbetaL-EK admitted from other sites suggest that greater emphasis must be placed on controlling the spread of such organisms within and between institutions.

Topics: Academic Medical Centers; Adult; Aged; Aged, 80 and over; Ampicillin; Anti-Bacterial Agents; beta-Lactam Resistance; Carrier State; Case-Control Studies; Cefepime; Cephalosporins; Cross Infection; Drug Therapy, Combination; Drug Utilization Review; Escherichia coli Infections; Feces; Female; Formularies, Hospital as Topic; Gentamicins; Hospitals, Community; Hospitals, Urban; Humans; Infection Control; Klebsiella Infections; Length of Stay; Male; Middle Aged; Pennsylvania; Prevalence; Risk Factors; Sulbactam

A mouse model of bacteremia was used to compare the efficacies of 1.5- and 3.0-g intravenous doses of ampicillin-sulbactam. Seven strains of Escherichia coli producing various levels of TEM-1 beta-lactamase were used as the challenge isolates. These strains included six clinical isolates (MICs from 2/1 micrograms/ml [with 2 and 1 microgram/ml being the respective concentrations of ampicillin and sulbactam] to 32/16 micrograms/ml) with similar degrees of virulence in mice and a laboratory genetic transformant (E. coli AFE) which hyperproduces TEM-1 (MIC = 128/64 micrograms/ml). Human pharmacokinetics were simulated by injecting mice subcutaneously twice (1 h apart) with ampicillin-sulbactam at concentrations of 40 mg/kg of body weight (1.5 g) and 80 mg/kg (3.0 g). Against two clinical isolates for which ampicillin-sulbactam MICs were < or = 8/4 micrograms/ml, no difference was observed in either the rate or level of killing between the two doses, and both doses were 100% protective against lethal infection. Against the four clinical isolates for which ampicillin-sulbactam MICs were between 16/8 and 32/16 micrograms/ml, a slight delay in killing was noted with three of the strains. This delay was followed by a rapid 2- to 3-log drop in the level of bacteremia, and both doses of ampicillin-sulbactam were 100% protective against lethal septicemia. With strain AFE, no killing was observed with the 40-mg/kg dose compared with a 2-log killing with the 80-mg/kg dose. This difference in killing correlated with a decreased protective efficacy of the 40-mg/kg dose. These data suggest that the 1.5-g preparation of ampicillin-sulbactam is as effective as the 3.0-g dose in the treatment of experimentally induced E. coli bacteremia, as long as ampicillin-sulbactam MICs are 32/16 micrograms/ml or less.

Topics: Ampicillin; Animals; Bacteremia; Dose-Response Relationship, Drug; Drug Therapy, Combination; Escherichia coli Infections; Male; Mice; Sulbactam

A reversible cardiogenic shock model in pigs investigated shock-induced changes in the pharmacokinetics and tissue distribution of ampicillin-sulbactam and the efficacy of this antibiotic regimen in eliminating enteric bacterial translocation. Sixteen pigs were randomly allocated to 3 groups: group I (shock, ampicillin-sulbactam, n = 6), group II (no shock, ampicillin-sulbactam, n = 6), and group III (shock, no ampicillin-sulbactam, n = 4). Nalidixic acid-resistant E. coli (60 x 10(6) CFU) were instilled into a jejunal loop created in each pig, and bacterial cultures were taken from thoracic duct lymph, periportal, and mesenteric lymph nodes. Ampicillin-sulbactam was administered intravenously at a standard dose of 3 g. Results showed that 1) ampicillin and sulbactam concentrations generally increase during cardiogenic shock; 2) cardiogenic shock does not increase ampicillin concentrations in jejunum and liver; 3) during resuscitation, thoracic duct lymph ampicillin concentrations decrease; and 4) during and immediately after cardiogenic shock, standard doses of ampicillin-sulbactam appear efficacious in eliminating translocated bacteria.

Topics: Ampicillin; Animals; Ascitic Fluid; Bacteria; Cardiac Output; Drug Therapy, Combination; Escherichia coli Infections; Female; Intestinal Mucosa; Liver; Lung; Lymph; Lymph Nodes; Mesentery; Portal System; Shock, Cardiogenic; Sulbactam; Swine; Tissue Distribution

In a modified pregnant rabbit model using intracervical inoculation of Escherichia coli we investigated the effects of administration of delayed antibiotics and indomethacin on outcomes.. We inoculated 10(5) colony-forming units of Escherichia coli or saline solution bilaterally in the cervix of New Zealand White rabbits at 70% of gestation and assigned animals to ampicillin-sulbactam therapy beginning at 0, 4, 8, 12, and 16 hours after inoculation with Escherichia coli or to no antibiotic therapy. We alternated indomethacin pretreatment in rabbits receiving no antibiotic therapy and rabbits starting ampicillin-sulbactam 4 hours after inoculation.. Compared with saline solution inoculated control animals, those inoculated with Escherichia coli (and given no antibiotic therapy) had significant increases in fetal loss, fever, bleeding at 24 hours, and positive cultures (100%, 92%, 76%, 98% versus 0%, respectively, all p < 0.01). In Escherichia coli-inoculated animals receiving no antibiotic therapy pretreatment with indomethacin significantly decreased bleeding and delivery within first 24 hours compared with those not treated with indomethacin (p < 0.05) but did not significantly improve fetal survival. Ampicillin-sulbactam treatment stated at 0, 4, 8, and 12 hours after inoculation resulted in improved fetal survival compared with the untreated group (100%, 56%, 50%, 50% versus 0%, respectively, all p < 0.05). Treatment initiated at 16 hours resulted in outcomes similar to Escherichia coli-inoculated animals receiving no antibiotic therapy.. Intracervical Escherichia coli inoculation produced infection in the uterus and uniform pregnancy loss. Pretreatment with indomethacin did not result in improved fetal survival. Ampicillin-sulbactam therapy, initiated as long as 12 hours after Escherichia coli inoculation, resulted in significant improvement in fetal survival compared with antibiotic therapy. We believe this model mimics ascending infection in pregnancy more closely than do previous animal models.

Topics: Ampicillin; Animals; Chorioamnionitis; Disease Models, Animal; Drug Therapy, Combination; Escherichia coli Infections; Female; Indomethacin; Pregnancy; Pregnancy Complications, Infectious; Premedication; Rabbits; Sulbactam; Time Factors; Treatment Outcome; Uterine Cervical Diseases

We examined the efficacy of ampicillin-sulbactam (2:1) and cefoxitin in the treatment of infections caused by Escherichia coli strains exhibiting increasing levels of beta-lactamase-mediated resistance to ampicillin-sulbactam in the rat intra-abdominal abscess model. Cefoxitin was superior to ampicillin-sulbactam in the treatment of infections caused by all strains. Treatment with ampicillin-sulbactam resulted in a statistically significant decrease in CFU per gram of abscess in comparison with treatment with ampicillin alone for both the moderately resistant and the resistant strains, with an inverse correlation between the MIC and the absolute decrease in CFU per gram of abscess.

Topics: Abdomen; Abscess; Ampicillin; Animals; Cefoxitin; Colony Count, Microbial; Drug Therapy, Combination; Escherichia coli Infections; Male; Microbial Sensitivity Tests; Rats; Rats, Sprague-Dawley; Sulbactam

We evaluated the pharmacokinetics and therapeutic efficacy of ampicillin combined with sulbactam in a rabbit model of meningitis due to a beta-lactamase-producing strain of Escherichia coli K-1. Ceftriaxone was used as a comparison drug. The MIC and MBC were 32 and greater than 64 micrograms/ml (ampicillin), greater than 256 and greater than 256 micrograms/ml (sulbactam), 2.0 and 4.0 micrograms/ml (ampicillin-sulbactam [2:1 ratio, ampicillin concentration]) and 0.125 and 0.25 micrograms/ml (ceftriaxone). All antibiotics were given by intravenous bolus injection in a number of dosing regimens. Ampicillin and sulbactam achieved high concentrations in cerebrospinal fluid (CSF) with higher dose regimens, but only moderate bactericidal activity compared with that of ceftriaxone was obtained. CSF bacterial titers were reduced by 0.6 +/- 0.3 log10 CFU/ml/h with the highest ampicillin-sulbactam dose used (500 and 500 mg/kg of body weight, two doses). This was similar to the bactericidal activity achieved by low-dose ceftriaxone (10 mg/kg), while a higher ceftriaxone dose (100 mg/kg) produced a significant increase in bactericidal activity (1.1 +/- 0.4 log10 CFU/ml/h). It appears that ampicillin-sulbactam, despite favorable CSF pharmacokinetics in animals with meningitis, may be of limited value in the treatment of difficult-to-treat beta-lactamase-producing bacteria, against which the combination shows only moderate in vitro activity.

Topics: Ampicillin; Animals; beta-Lactamases; Ceftriaxone; Drug Therapy, Combination; Escherichia coli Infections; Injections, Intravenous; Meningitis, Bacterial; Microbial Sensitivity Tests; Rabbits; Sulbactam

We conducted experiments with a previously described rabbit model of Escherichia coli-induced preterm pregnancy loss. Does at 70% gestation were inoculated hysteroscopically with 0.2 ml of Escherichia coli (10(5) colony-forming units per milliliter) or saline solution. Animals were randomly assigned to either receive treatment with ampicillin-sulbactam (begun 1 to 2 hours before inoculation and continued for up to 7 days) or to receive no therapy. Animals were killed after delivery or after 7 days. Saline solution-inoculated animals had no pregnancy loss. Of the Escherichia coli-inoculated animals, those treated with ampicillin-sulbactam had significantly fewer deliveries, fewer positive cultures, and more live fetuses than the untreated animals (p less than or equal to 0.001). Cultures from multiple sites, amniotic fluid prostaglandin levels, and maternal progesterone levels were obtained, and the placenta, uterus, and fetal lung were histologically evaluated. In the second phase of the study, the Escherichia coli-inoculated animals were treated with ampicillin-sulbactam at one of three times: at inoculation or 2 or 4 hours after inoculation. The Escherichia coli-inoculated does treated with ampicillin-sulbactam at or before inoculation had significantly fewer deliveries, fewer positive cultures, and more live fetuses than the Escherichia coli-inoculated does in which treatment was delayed 4 hours (p less than or equal to 0.01).

Topics: Ampicillin; Animals; Disease Models, Animal; Drug Therapy, Combination; Escherichia coli Infections; Female; Fetal Death; Injections, Intramuscular; Pregnancy; Pregnancy Complications, Infectious; Progesterone; Rabbits; Sulbactam; Time Factors

Cefamandole, cefoxitin, cefotetan, ceftizoxime, imipenem plus cilastatin, and ampicillin plus sulbactam were compared in the eradication of subcutaneous abscess in mice caused by Bacteroides fragilis group organisms and Escherichia coli alone or in combination. The abscesses were examined 5 d after inoculation. B. fragilis group reached log10.1-11.0 organisms per abscess and E. coli log11.6-12.5. Imipenem plus cilastatin significantly reduced (in 6.9-10.6 logs) the number of E. coli and all members of B. fragilis group alone or in all combinations. Ampicillin plus sulbactam reduced the numbers of all B. fragilis group (in 4.2-7.2 logs) but was less effective against E. coli (reduction of 1.8-4.2 logs). Cefoxitin was effective in significantly reducing (in 4.9-6.2 logs) the number of E. coli and all members of B. fragilis group alone or in all combinations. Cefotetan was effective against B. fragilis (reduction of 5.1-6.6 logs) and E. coli alone or in combination but did not reduce the number of Bacteroides thetaiotaomicron, Bacteroides vulgatus, and Bacteroides ovatus. Ceftizoxime was effective against only B. ovatus (reduction of 3.7-5.8) and E. coli (reduction of 6.0-8.1 logs); it did not reduce the number of other organisms. Cefamandole was effective against only E. coli and was not effective against any member of the B. fragilis group. These in vivo data confirm the in vitro activity of these antimicrobials.

Topics: Abscess; Ampicillin; Animals; Anti-Bacterial Agents; Bacteroides fragilis; Bacteroides Infections; Cefamandole; Cefotetan; Cefoxitin; Ceftizoxime; Cilastatin; Cilastatin, Imipenem Drug Combination; Disease Models, Animal; Drug Combinations; Drug Therapy, Combination; Escherichia coli; Escherichia coli Infections; Imipenem; Male; Mice; Skin Diseases; Sulbactam