ro13-9904 and Klebsiella-Infections

To review the laboratory diagnosis of extended-spectrum beta-lactamase (ESBL) and AmpC beta-lactamase-producing bacteria and evaluate potential treatment options.. A PubMed search, restricted to English-language articles, was conducted (1966-May 2007) using the search terms ESBL, AmpC, diagnosis, detection, carbapenem, ertapenem, fluoroquinolone, cephalosporin, cefepime, tigecycline, and colistin. Additional references were identified through review of bibliographies of identified articles.. All studies that evaluated laboratory methods for the detection of ESBLs and AmpC beta-lactamases and/or the treatment of these organisms were reviewed. All articles that were deemed to be clinically pertinent were included and critically evaluated.. Numerous laboratory techniques are available for the detection of ESBLs. In contrast, laboratory techniques for detection of AmpC beta-lactamases are limited, particularly for plasmid-mediated AmpC beta-lactamases. Routine microbiologic testing may not detect ESBLs or AmpC beta-lactamases. Optimal antibiotic treatment options are derived from limited observational studies and case reports. Randomized clinical trials evaluating appropriate antibiotic treatment options are lacking. In vitro susceptibility does not always correlate with clinical outcomes. The use of imipenem was associated with the lowest incidence of mortality in patients with bacteremia due to ESBL-producing organisms.. Laboratory detection of ESBLs for most organisms is possible with Clinical and Laboratory Standards Institute-recommended testing. However, these tests can be associated with both false negative and false positive results, particularly with organisms that harbor both ESBL- and plasmid-mediated AmpC beta-lactamases. No established guidelines exist for the detection of AmpC beta-lactamases. Imipenem and meropenem are superior to other antibiotics for the treatment of serious infections due to ESBL and AmpC beta-lactamase-producing gram-negative bacteria. While in vitro data demonstrate that tigecycline, ertapenem, and colistin might be potential choices, clinical experience is lacking.

Topics: Aged, 80 and over; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Ceftriaxone; Drug Resistance, Multiple, Bacterial; Humans; Imipenem; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Microbial Sensitivity Tests; Pneumonia, Bacterial; Thienamycins

Ceftriaxone is the preferred treatment for bacteraemia caused by non-MDR (antibiotic-susceptible) Klebsiella pneumoniae. Excessive and widespread ceftriaxone use creates selection pressure for ESBLs. Cefazolin is an alternative, although there are theoretical concerns that SHV-1 β-lactamase in K. pneumoniae may inactivate cefazolin in an inoculum-dependent manner.. In this retrospective study, we investigated the outcomes in K. pneumoniae bacteraemia patients treated with IV cefazolin versus IV ceftriaxone as definitive therapy.. A total of 917 patients infected with K. pneumoniae from 1 January to 31 December 2016 in three public acute care hospitals in Singapore were screened for study eligibility. Consecutive unique episodes of monomicrobial bacteraemia caused by cefazolin- and/or ceftriaxone-susceptible K. pneumoniae were analysed (n = 284).. There were 143 patients (50.4%) in the cefazolin group and 141 patients (49.6%) in the ceftriaxone group. Demographics, baseline illness severity and risk factors for healthcare-associated bacteraemia were comparable in the two treatment groups. The primary outcome of 28 day all-cause mortality was not significantly different between the cefazolin and ceftriaxone groups (10.5% versus 7.1%, P = 0.403). Both in the crude analysis and using a multivariable logistic regression model with inverse probability weighting based on propensity score, cefazolin treatment was not associated with increased risk of 28 day mortality (OR 1.51 with ceftriaxone as the reference group, 95% CI 0.67-3.53; adjusted OR 1.55, 95% CI 0.33-7.40).. Cefazolin may be a ceftriaxone-sparing alternative treatment for antibiotic-susceptible K. pneumoniae bacteraemia. This observation may provide sufficient clinical equipoise for a randomized controlled trial.

Topics: Anti-Bacterial Agents; Bacteremia; Cefazolin; Ceftriaxone; Humans; Klebsiella Infections; Klebsiella pneumoniae; Retrospective Studies; Singapore

Klebsiella pneumoniae liver abscess (KLA) is emerging worldwide due to hypermucoviscous strains with a propensity for metastatic infection. Treatment includes drainage and prolonged intravenous antibiotics. We aimed to determine whether oral antibiotics were noninferior to continued intravenous antibiotics for KLA.. This noninferiority, parallel group, randomized, clinical trial recruited hospitalized adults with liver abscess and K. pneumoniae isolated from blood or abscess fluid who had received ≤7 days of effective antibiotics at 3 sites in Singapore. Patients were randomized 1:1 to oral (ciprofloxacin) or intravenous (ceftriaxone) antibiotics for 28 days. If day 28 clinical response criteria were not met, further oral antibiotics were prescribed until clinical response was met. The primary endpoint was clinical cure assessed at week 12 and included a composite of absence of fever in the preceding week, C-reactive protein <20 mg/L, and reduction in abscess size. A noninferiority margin of 12% was used.. Between November 2013 and October 2017, 152 patients (mean age, 58.7 years; 25.7% women) were recruited, following a median 5 days of effective intravenous antibiotics. A total of 106 (69.7%) underwent abscess drainage; 71/74 (95.9%) randomized to oral antibiotics met the primary endpoint compared with 72/78 (92.3%) randomized to intravenous antibiotics (risk difference, 3.6%; 2-sided 95% confidence interval, -4.9% to 12.8%). Effects were consistent in the per-protocol population. Nonfatal serious adverse events occurred in 12/72 (16.7%) in the oral group and 13/77 (16.9%) in the intravenous group.. Oral antibiotics were noninferior to intravenous antibiotics for the early treatment of KLA.. NCT01723150.

Topics: Adult; Anti-Bacterial Agents; Ceftriaxone; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Liver Abscess; Male; Middle Aged; Singapore

Extended-spectrum β-lactamases mediate resistance to third-generation cephalosporins (eg, ceftriaxone) in Escherichia coli and Klebsiella pneumoniae. Significant infections caused by these strains are usually treated with carbapenems, potentially selecting for carbapenem resistance. Piperacillin-tazobactam may be an effective "carbapenem-sparing" option to treat extended-spectrum β-lactamase producers.. To determine whether definitive therapy with piperacillin-tazobactam is noninferior to meropenem (a carbapenem) in patients with bloodstream infection caused by ceftriaxone-nonsusceptible E coli or K pneumoniae.. Noninferiority, parallel group, randomized clinical trial included hospitalized patients enrolled from 26 sites in 9 countries from February 2014 to July 2017. Adult patients were eligible if they had at least 1 positive blood culture with E coli or Klebsiella spp testing nonsusceptible to ceftriaxone but susceptible to piperacillin-tazobactam. Of 1646 patients screened, 391 were included in the study.. Patients were randomly assigned 1:1 to intravenous piperacillin-tazobactam, 4.5 g, every 6 hours (n = 188 participants) or meropenem, 1 g, every 8 hours (n = 191 participants) for a minimum of 4 days, up to a maximum of 14 days, with the total duration determined by the treating clinician.. The primary outcome was all-cause mortality at 30 days after randomization. A noninferiority margin of 5% was used.. Among 379 patients (mean age, 66.5 years; 47.8% women) who were randomized appropriately, received at least 1 dose of study drug, and were included in the primary analysis population, 378 (99.7%) completed the trial and were assessed for the primary outcome. A total of 23 of 187 patients (12.3%) randomized to piperacillin-tazobactam met the primary outcome of mortality at 30 days compared with 7 of 191 (3.7%) randomized to meropenem (risk difference, 8.6% [1-sided 97.5% CI, -∞ to 14.5%]; P = .90 for noninferiority). Effects were consistent in an analysis of the per-protocol population. Nonfatal serious adverse events occurred in 5 of 188 patients (2.7%) in the piperacillin-tazobactam group and 3 of 191 (1.6%) in the meropenem group.. Among patients with E coli or K pneumoniae bloodstream infection and ceftriaxone resistance, definitive treatment with piperacillin-tazobactam compared with meropenem did not result in a noninferior 30-day mortality. These findings do not support use of piperacillin-tazobactam in this setting.. anzctr.org.au Identifiers: ACTRN12613000532707 and ACTRN12615000403538 and ClinicalTrials.gov Identifier: NCT02176122.

Topics: Adult; Aged; Anti-Bacterial Agents; Bacteremia; Cause of Death; Ceftriaxone; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Thienamycins

Gram-negative bacteria such as Escherichia coli or Klebsiella spp. frequently cause bloodstream infections. There has been a worldwide increase in resistance in these species to antibiotics such as third generation cephalosporins, largely driven by the acquisition of extended-spectrum beta-lactamase or plasmid-mediated AmpC enzymes. Carbapenems have been considered the most effective therapy for serious infections caused by such resistant bacteria; however, increased use creates selection pressure for carbapenem resistance, an emerging threat arising predominantly from the dissemination of genes encoding carbapenemases. Recent retrospective data suggest that beta-lactam/beta-lactamase inhibitor combinations, such as piperacillin-tazobactam, may be non-inferior to carbapenems for the treatment of bloodstream infection caused by extended-spectrum beta-lactamase-producers, if susceptible in vitro. This study aims to test this hypothesis in an effort to define carbapenem-sparing alternatives for these infections.. The study will use a multicentre randomised controlled open-label non-inferiority trial design comparing two treatments, meropenem (standard arm) and piperacillin-tazobactam (carbapenem-sparing arm) in adult patients with bacteraemia caused by E. coli or Klebsiella spp. demonstrating non-susceptibility to third generation cephalosporins. Recruitment is planned to occur in sites across three countries (Australia, New Zealand and Singapore). A total sample size of 454 patients will be required to achieve 80% power to determine non-inferiority with a margin of 5%. Once randomised, definitive treatment will be for a minimum of 4 days, but up to 14 days with total duration determined by treating clinicians. Data describing demographic information, antibiotic use, co-morbid conditions, illness severity, source of infection and other risk factors will be collected. Vital signs, white cell count, use of vasopressors and days to bacteraemia clearance will be recorded up to day 7. The primary outcome measure will be mortality at 30 days, with secondary outcomes including days to clinical and microbiological resolution, microbiological failure or relapse, isolation of a multi-resistant organism or Clostridium difficile infection.. The MERINO trial is registered under the Australian New Zealand Clinical Trials Register (ANZCTR), reference number: ACTRN12613000532707 (registered 13 May 2013) and the US National Institute of Health ClinicalTrials.gov register, reference number: NCT02176122 (registered 24 June 2014).

Topics: Adult; Anti-Bacterial Agents; Bacteremia; Ceftriaxone; Clinical Protocols; Drug Resistance, Microbial; Escherichia coli Infections; Humans; Klebsiella Infections; Meropenem; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Sample Size; Thienamycins

Klebsiella pneumoniae liver abscess is the most common etiology of liver abscess in Singapore and much of Asia, and its incidence is increasing. Current management includes prolonged intravenous antibiotic therapy, but there is limited evidence to guide oral conversion. The implicated K1/K2 capsule strain of Klebsiella pneumoniae is almost universally susceptible to ciprofloxacin, an antibiotic with high oral bioavailability. Our primary aim is to compare the efficacy of early (< one week) step-down to oral antibiotics, to continuing four weeks of intravenous antibiotics, in patients with Klebsiella liver abscess.. The study is designed as a multi-center randomized open-label active comparator-controlled non-inferiority trial, with a non-inferiority margin of 12%. Eligible participants will be inpatients over the age of 21 with a CT or ultrasound scan suggestive of a liver abscess, and Klebsiella pneumoniae isolated from abscess fluid or blood. Randomization into intervention or active control arms will be performed with a 1:1 allocation ratio. Participants randomized to active control will receive IV ceftriaxone 2 grams daily to complete a total of four weeks of IV antibiotics. Participants randomized to intervention will be immediately converted to oral ciprofloxacin 750 mg twice daily. At Week four, all participants will undergo abdominal imaging and be assessed for clinical response (CRP < 20 mg/l, absence of fever, plus scan showing that the maximal diameter of the abscess has reduced). If criteria are met, antibiotics are stopped; if not, oral antibiotics are continued, with reassessment for clinical response fortnightly. If criteria for clinical response are met by Week 12, the primary endpoint of clinical cure is met. A cost analysis will be performed to assess the cost saving of early conversion to oral antibiotics, and a quality of life analysis will be performed to assess whether treatment with oral antibiotics is less burdensome than prolonged IV antibiotics.. Our results would help inform local and international practice guidelines regarding the optimal antibiotic management of Klebsiella liver abscess. A finding of non-inferiority may translate to the wider adoption of a more cost-effective strategy that reduces hospital length of stay and improves patient-centered outcomes and satisfaction.. Clinical trials gov NCT01723150.

Topics: Administration, Intravenous; Administration, Oral; Anti-Bacterial Agents; Ceftriaxone; Ciprofloxacin; Clinical Protocols; Cost-Benefit Analysis; Drug Administration Schedule; Drug Costs; Hospital Costs; Hospitals, Teaching; Humans; Klebsiella Infections; Klebsiella pneumoniae; Liver Abscess; Quality of Life; Research Design; Singapore; Time Factors; Treatment Outcome

The combination of penicillin with an aminoglycoside has been recommended as an initial treatment of choice for patients with acute infections of the biliary tract. However, many patients have incidence of renal problems and for this reason aminoglycosides must be avoided. Newer antimicrobial agents with lesser nephrotoxic effects will be tried. We, therefore, performed a prospective, randomized trial of ofloxacin, a new quinolone and ceftriaxone in patients with acute biliary tract infections. Fifty-two patients with severe biliary tract infections (cholecystitis and cholangitis) were randomly assigned to receive either ofloxacin (n = 28) or ceftriaxone (n = 24). The 2 groups receiving antibiotics were similar with respect to all clinical and laboratory parameters. Bacteria were documented in 48% of patients in the ofloxacin group and in 46% in the ceftriaxone group. The percentage of patients with a clinical cure or significant improvement was the same in the 2 groups. No significant difference was noted between the 2 treatment groups with respect to drug toxicity. These data suggest that intravenous ofloxacin followed by oral administration is an effective and safe single drug for the therapy of patients with acute biliary tract infections.

Topics: Anti-Infective Agents; Bacteremia; Ceftriaxone; Cephalosporins; Cholangitis; Cholecystitis; Escherichia coli Infections; Female; Gram-Negative Bacterial Infections; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Middle Aged; Ofloxacin; Phlebitis

Ceftriaxone effectively inhibited 332 out of 452 (73.45%) bacterial strains in vitro tests. 291 out of 365 (79.69%) gram negative and 41 out of 87 (47.12%) gram positive strains were inhibited. The tests showed ceftriaxone to be more effective than cephalothin, cephotaxime, cephuroxime, cephamandol and cephoxitin. Kinetic tests showed that cephtriaxone has a plasmatic half life of 7.25 hrs. 24 hours after administration of a 1000 mg venous bolus the drug was still present in the blood. Urinary elimination over a 24 hr. period amounted to means 486.8 mg (48.68%). The drug has liquor transfer capacity. 37 of the 38 patients treated showed complete clinical or clinicobacteriological cure. Improvement was noted in the 38th.

Topics: Adolescent; Adult; Aged; Cefotaxime; Ceftriaxone; Child; Child, Preschool; Clinical Trials as Topic; Female; Gram-Negative Bacteria; Gram-Positive Bacteria; Half-Life; Humans; Kinetics; Klebsiella Infections; Male; Meningitis; Middle Aged; Respiratory Tract Infections; Staphylococcal Infections; Streptococcal Infections

Cefepime is a first-line agent for empiric sepsis therapy; however, cefepime use may be associated with increased mortality for extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E) in an MIC-dependent manner. This study aimed to compare the efficacy of empiric cefepime versus meropenem for bloodstream infections (BSI) caused by ceftriaxone-resistant Escherichia coli and Klebsiella pneumoniae with cefepime MICs ≤ 2 mg/L.. This single-center retrospective cohort study included patients admitted from October 2010 to August 2020 who received cefepime or meropenem empirically for sepsis with a blood culture growing ceftriaxone-resistant Escherichia coli or Klebsiella pneumoniae. The primary outcome was 30-day mortality; secondary endpoints included 14-day mortality, recurrent BSI, readmission and recurrent infection within 90 days, time to clinical resolution of infection, time to clinical stability, and clinical stability at 48 hours.. Fifty-four patients met inclusion criteria: 36 received meropenem and 18 received cefepime. The median (IQR) treatment durations of cefepime and meropenem were 3 (2-6) days and 7 (5-10) days, respectively. Thirty-day and 14-day mortality were similar between cefepime and meropenem (11.1% vs. 2.8%; P = 0.255 and 5.6% vs. 2.8%; P = 1.00, respectively). Cefepime was associated with longer time to clinical stability compared with meropenem (median 38.48 hours vs. 21.26; P = 0.016).. Mortality was similar between groups, although most patients who received cefepime empirically were ultimately transitioned to a carbapenem to complete the full treatment course. Empiric cefepime was associated with a delay in achieving clinical stability when compared with meropenem to treat BSI caused by ceftriaxone-resistant Enterobacterales, even when cefepime-susceptible.

Topics: Anti-Bacterial Agents; Bacteremia; beta-Lactamases; Cefepime; Ceftriaxone; Escherichia coli; Escherichia coli Infections; Humans; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Retrospective Studies; Sepsis

Urinary tract infections (UTIs) and bacterial resistance to antibiotics is global health problem and a threat to public health in many countries.. The study aimed to determine the prevalence of MDR Escherichia coli and Klebsiella pneumoniae in UTI patients.. The midstream urine samples of 120 patients were collected and cultured as described by the protocols at the respective sample collection sites on MacConkey Blood agar. Samples were tested by using the fully automated VITEK 2 Compact system for Gram-negative identification and detection of antimicrobial susceptibility of microorganisms.. The most prevalent pathogen was E. coli, which was found in 82 (68.3%) urine samples, followed by K. pneumonia, found in 38 (31.7%) urine samples. As far as antibiotic resistance is concerned, E. coli isolates were found to be highly resistant for ceftriaxone (89.0% of the isolates), ampicillin (86.6%), levofloxacin (82.9%), cefotaxime (79.3%), aztreonam (74.4%), ceftazidime (68.3%) and gentamicin, piperacillin, and trimethoprim-sulfamethoxazole, 54.9 and 53.7%, respectively. The E. coli isolates were found to be relatively less resistant to imipenem (2.4%), cefepime (34.1%), and ciprofloxacin (35.4%). For K. pneumonia isolates, high resistance rates were observed for piperacillin (81.6%), levofloxacin (78.9%), ampicillin (76.3%), cefotaxime (73.7%), trimethoprim-sulfamethoxazole (71.1%), ceftazidime (65.8%), gentamicin (63.2%), cefepime (50.0%), and aztreonam (44.7%). However, moderate resistance rates were detected for these were found to be less resistant for imipenem (13.2%), ceftriaxone (31.6%), and ciprofloxacin (36.8%).. E. coli and K. pneumoniae from the clinical isolates displayed high resistance to many antibiotics in UTI patients.

Topics: Ampicillin; Anti-Bacterial Agents; Aztreonam; Cefepime; Ceftazidime; Ceftriaxone; Ciprofloxacin; Drug Resistance, Multiple; Escherichia coli; Escherichia coli Infections; Gentamicins; Humans; Imipenem; Klebsiella Infections; Klebsiella pneumoniae; Levofloxacin; Microbial Sensitivity Tests; Piperacillin; Prevalence; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections

Klebsiella variicola is a pathogen that is increasingly recognized as being associated with human infections, but the methods available to clinical microbiology laboratories for accurate identification are limited. In this study, we assessed the accuracy of identification of

Topics: Ceftriaxone; Humans; Klebsiella; Klebsiella Infections; Klebsiella pneumoniae; Laboratories; Meropenem; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

An immunocompetent 49-year-old man presented with swelling and pain in the lower region of his left leg that had lasted for 4 weeks. The diagnosis was severe pyomyositis and osteomyelitis in the lower left leg caused by hypervirulent

Topics: Ceftriaxone; Humans; Klebsiella Infections; Klebsiella pneumoniae; Liver Abscess, Pyogenic; Male; Middle Aged; Osteomyelitis; Pyomyositis

Topics: Abscess; Administration, Oral; Aged; Anti-Bacterial Agents; Ceftriaxone; Diabetes Mellitus, Type 2; Diagnosis, Differential; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Prostatic Diseases; Prostatic Hyperplasia; Tomography, X-Ray Computed

Klebsiella pneumoniae is a well-known pathogen and contributes to different types of infection. To investigate the antibiotic resistance profiles and prevalence of class I, II, and III integrons among clinical isolates of K. pneumoniae, a total of 142 non-duplicate clinical isolates were collected. Antibiotic susceptibility was assessed using Kirby-Bauer disk diffusion method and Clinical and Laboratory Standards Institute (CLSI) guidelines. Polymerase chain reaction (PCR) method was used to identify class I, II and III integrons. The isolates were mostly resistant against streptomycin (62 strains, 43.7 %) and ceftriaxone (42 strains, 29.6 %). Twenty-six (18.3%) isolates were found to be multi-drug resistant (MDR). Class I and II integrons were detected in 65 isolates (45.8%) and 1 (0.7%) isolate, respectively. The findings of this study revealed that the prevalence of streptomycin-resistant isolates is high, and its use must be restricted. Also, our results revealed that class I integrons are widely prevalent in clinical isolates of K. pneumoniae and a significant association was observed between resistance against imipenem, ciprofloxacin, gentamicin and streptomycin and the presence of integrons, necessitating appropriate infection control programs.

Topics: Anti-Bacterial Agents; Cefepime; Ceftriaxone; Ciprofloxacin; Drug Resistance, Multiple, Bacterial; Female; Guidelines as Topic; Humans; Integrons; Klebsiella Infections; Klebsiella pneumoniae; Male; Polymerase Chain Reaction; Pseudomonas aeruginosa; Streptomycin

Topics: Alcoholism; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Ceftriaxone; Diabetes Mellitus; Drainage; Drug Therapy, Combination; Humans; Klebsiella Infections; Klebsiella pneumoniae; Liver Abscess, Pyogenic; Male; Metronidazole; Middle Aged

Topics: Ceftriaxone; Epidural Abscess; Humans; Klebsiella Infections; Klebsiella pneumoniae; Leg; Male; Mastoidectomy; Middle Aged; Muscle Weakness; Surgical Wound Infection; Vancomycin

There are scarce data describing the etiology and clinical sequelae of sepsis in low- and middle-income countries (LMICs). This study describes the prevalence and etiology of sepsis among critically ill patients at a referral hospital in Malawi. We conducted an observational prospective cohort study of adults admitted to the intensive care unit or high-dependency unit (HDU) from January 29, 2018 to March 15, 2018. We stratified the cohort based on the prevalence of sepsis as defined in the following three ways: quick sequential organ failure assessment (qSOFA) score ≥ 2, clinical suspicion of systemic infection, and qSOFA score ≥ 2 plus suspected systemic infection. We measured clinical characteristics and blood and urine cultures for all patients; antimicrobial sensitivities were assessed for positive cultures. During the study period, 103 patients were admitted and 76 patients were analyzed. The cohort comprised 39% male, and the median age was 30 (interquartile range: 23-40) years. Eighteen (24%), 50 (66%), and 12 patients (16%) had sepsis based on the three definitions, respectively. Four blood cultures (5%) were positive, two from patients with sepsis by all three definitions and two from patients with clinically suspected infection only. All blood bacterial isolates were multidrug resistant. Of five patients with urinary tract infection, three had sepsis secondary to multidrug-resistant bacteria. Hospital mortality for patients with sepsis based on the three definitions ranged from 42% to 75% versus 12% to 26% for non-septic patients. In summary, mortality associated with sepsis at this Malawi hospital is high. Bacteremia was infrequently detected, but isolated pathogens were multidrug resistant.

Topics: Adult; Anti-Bacterial Agents; Antifungal Agents; Bacteremia; Burkholderia Infections; Candida glabrata; Candidiasis, Invasive; Ceftriaxone; Cohort Studies; Critical Illness; Drug Resistance, Multiple, Bacterial; Escherichia coli Infections; Female; Gram-Positive Bacterial Infections; Hospital Mortality; Humans; Intensive Care Units; Klebsiella Infections; Malawi; Male; Metronidazole; Microbial Sensitivity Tests; Middle Aged; Prevalence; Prospective Studies; Proteus Infections; Sepsis; Staphylococcal Infections; Urinary Tract Infections; Young Adult

Klebsiella pneumoniae is an important multi-drug-resistant Gram-negative pathogen, associated with nosocomially acquired infections. This study aimed to determine the genotypic and phenotypic characterization of Klebsiella pneumoniae isolates and to correlate the antibiotic resistance with the presence of virulence genes revealed by molecular genotypic testing in Riyadh, Saudi Arabia.. About 23 Klebsiella pneumoniae isolates were collected from various specimen types. Identification of the organisms was carried out. Antimicrobial susceptibility performed against 12 antibiotics. The DNA was isolated and purified then genotypic confirmation was done through polymerase chain reactions (PCR) to detect TEM, SHV, CTX-M, IMP and KPC genes. PCR products were sequenced and aligned with GenBank sequences.. Out of 23 isolates of K. pneumoniae, the majority (43.5%) was from tracheal aspirate. The percentage of females (65.2%) was more than males (34.8%). The highest isolates prevalence was found in the age group of >58 (39.1%). About 100% of isolates were resistant to cefotaxime, ceftriaxone, ceftazidime, cefepime and ampicillin and 91.3% were sensitive to amikacin and Imipenem. Most isolates were SHV-9 gene positive (52.2%). It was found that tested isolates had 99-100% similarity when compared to GenBank sequences.. There was a preponderance of SHV-9 gene which suggests dissemination of the gene in the tested isolates.

Topics: Amikacin; Ampicillin; Anti-Bacterial Agents; beta-Lactamases; Cefepime; Cefotaxime; Ceftazidime; Ceftriaxone; DNA, Bacterial; Female; Genetic Variation; Genotype; Humans; Imipenem; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Polymerase Chain Reaction; Prevalence; Saudi Arabia; Virulence

We report a clonal outbreak of multidrug-resistant (MDR) Klebsiella variicola (sequence type [ST] 771) in a Bangladeshi neonatal unit from October 2016 to January 2017, associated with high mortality (54.5%). During the outbreak, K. variicola ST771 acquired an MDR plasmid harboring blaNDM-1, linked to high exposure to ceftriaxone and amikacin.

Topics: Amikacin; Anti-Bacterial Agents; Bangladesh; beta-Lactamases; Ceftriaxone; Disease Outbreaks; Drug Resistance, Multiple, Bacterial; Female; Genotype; Humans; Infant, Newborn; Klebsiella; Klebsiella Infections; Male; Plasmids; Survival Analysis

OXA-48 is an Ambler class D β-lactamase that hydrolyses penicillin and imipenem but has poor hydrolytic activity against cephalosporins. However, very few clinical experiences of treating extended-spectrum β-lactamase (ESBL)-negative OXA-48 producers with cephalosporins have been published.. The aim of this study was to report clinical experience of infections due to ESBL-negative OXA-48-producing Klebsiella pneumoniae (K. pneumoniae) treated with cephalosporins.. A retrospective study was conducted at Vall d'Hebron University Hospital, in Barcelona (Spain). It reviewed all microbiological isolates of OXA-48-producers that did not co-produce ESBL from May 2014 to May 2017, and included only clinical strains of patients treated with a cephalosporin for ≥72h.. From the 75 isolations of OXA-48 producers, there were 17 isolations of ESBL-negative OXA-48-producing K. pneumoniae. Three patients were treated with cephalosporins with successful outcomes: a pneumonia in a neutropenic patient treated with cefepime and amikacin; an acute focal nephritis of a renal graft treated with ceftriaxone; and an intrabdominal post-surgical infection treated with cefepime in combination with tigecycline at the beginning, and ciprofloxacin afterwards.. Cephalosporins could be an alternative treatment in selected patients with ESBL-negative OXA-48-producing K. pneumoniae infections, especially to avoid carbapenem use. However, it remains unknown if they should be given in combination.

Topics: Aged; Anti-Bacterial Agents; beta-Lactamases; Carbapenems; Cefepime; Ceftriaxone; Cephalosporins; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Middle Aged; Nephritis; Retrospective Studies; Spain

A 70-year-old man presented with acute wrist pain concerning for septic arthritis. Shortly thereafter, he developed acute monocular vision loss and was diagnosed with endogenous endophthalmitis. Subsequent imaging revealed numerous visceral abscesses and a mycotic abdominal aortic aneurysm. Cultures, in conjunction with the clinical syndrome, were strongly suggestive of hypervirulent

Topics: Administration, Intravenous; Aged; Arthritis, Infectious; Ceftriaxone; Diagnosis, Differential; Endophthalmitis; Humans; Klebsiella Infections; Klebsiella pneumoniae; Liver Abscess; Male; Treatment Outcome

Topics: Adult; beta-Lactamases; Ceftriaxone; Drug Resistance, Multiple, Bacterial; Escherichia coli; Escherichia coli Infections; Female; Gentamicins; Hospitals; Humans; Klebsiella Infections; Klebsiella pneumoniae; Maternal-Fetal Exchange; Piperacillin, Tazobactam Drug Combination; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Infectious; Tanzania; Urinary Tract Infections; Young Adult

Noma or cancrum oris is an orofacial gangrene causing progressive mutilating destruction of the infected tissues. It mainly affects malnourished children with poor oral hygiene and concurrent debilitating systemic illnesses. It is a polymicrobial infection and borrelia vincentii and fusobacterium are the most important pathogens known. We present a case of a boy aged 2.5 years with noma where klebsiella was grown and was the initial cause of failure of empiric therapy.

Topics: Anti-Bacterial Agents; Ceftriaxone; Child Nutrition Disorders; Child, Preschool; Humans; Infusions, Intravenous; Klebsiella Infections; Klebsiella pneumoniae; Male; Noma

The study was carried out to evaluate the clinical and bacteriological profile of SA in young infants (age ≤ 3 months) in a tertiary referral centre and to assess the risk factors and to document the changing trends in the epidemiology.. This was a prospective descriptive study on all young infants with SA. Clinical and perinatal history, examination, radiological and laboratory findings (blood count, ESR, CRP, blood and joint cultures) were studied. Emergency arthrotomy was done and antibiotics were administered in all patients.. Thirty young infants were included with a mean age of 22 ± 13.6 days and with male-to-female ratio 1.5:1. Pseudoparalysis and pain were the most common presenting symptoms. Knee joint was most commonly involved followed by hip. Ultrasound of the joint (86%) and elevated CRP levels (97%) were found to be reliable diagnostic markers. Most common causative organism was methicillin-resistant Staphylococcus aureus (43.3%) followed by Klebsiella pneumonia (23%). Sensitivity to empirical antibiotic regimen was lower (ceftriaxone 53%, amoxicillin 35%) when compared to higher antibiotics (gentamycin 88%, vancomycin 100%). Prematurity (57%), low birthweight (73%), anaemia (80%), previous history of hospitalisation (93%) and invasive procedures (90%) were found to be important risk factors.. The disease has distinct regional variations, and the epidemiological and bacterial profile is constantly changing. There is a shift in causative organisms towards more resistant and gram-negative species. Prematurity, low birthweight and previous hospitalisation are the major predisposing factors. A better understanding of the varied presentations is necessary for an early diagnosis and treatment, which is the most important prognostic factor.

Topics: Amoxicillin; Anti-Bacterial Agents; Arthritis, Infectious; Ceftriaxone; Female; Gentamicins; Hip Joint; Humans; Infant; Infant, Newborn; Klebsiella Infections; Klebsiella pneumoniae; Knee Joint; Male; Methicillin-Resistant Staphylococcus aureus; Osteomyelitis; Prospective Studies; Staphylococcal Infections; Vancomycin

Hypervirulent strains of Klebsiella pneumoniae are a recognized cause of a distinct invasive syndrome that results in pyogenic liver abscesses and metastatic complications, particularly in the Asia Pacific region. Reports of hypervirulent K.pneumoniae in Europe, the Americas and Australia indicate worldwide spread. We present a case of multi-focal osteomyelitis, a rarely described complication of hypervirulent K.pneumoniae in the medical literature. The prevalence of this condition in countries outside Asia may be expected to rise with increasing travel.. A 20-year-old Chinese man residing in Australia for 2 years presented with a 2-week history of gradually worsening leg pain preceded by 2 weeks of constitutional symptoms. Imaging with computerized axial tomography (CT) and other modalities revealed bilateral tibial lesions described as lattice-like linear lucencies involving the cortices with scalloping of the outer involved cortex. Cultures of tissue from a left tibial bone biopsy were positive cultures for K.pneumoniae. Whole-genome sequencing identified the isolate as K1 serotype ST23, a well-recognized hyper virulent strain capable of causing invasive disease. An abdominal CT revealed a 27x22mm liver abscess. The patient had no other metastatic manifestations of the disease, and responded to 6 weeks of intravenous ceftriaxone followed by 3 months of oral Ciprofloxacin.. Increased awareness of the manifestations and subsequent management of hyper virulent strains of K.pneumoniae by clinicians is important to assist early recognition and help minimize serious sequelae. Cases with overseas links, such as previous residence in the Asia Pacific area, are at higher risk for infection with the hyper virulent strain. This case highlights the need for clinicians to be able to recognize this important disease, especially in patients with the right epidemiological links, and to investigate and treat appropriately to prevent severe metastatic complications.

Topics: Asian People; Australia; Ceftriaxone; Humans; Klebsiella Infections; Klebsiella pneumoniae; Liver Abscess, Pyogenic; Male; Osteomyelitis; Serogroup; Whole Genome Sequencing; Young Adult

Liver abscess has formerly been a polymicrobial infection. Currently, liver abscess due to Klebsiella pneumoniae is increasingly reported, predominantly in Southeast Asia for unknown reasons. Liver abscess due to Klebsiella pneumonia has never been previously reported in Sri Lanka.. A 63-year-old Sinhalese man with diabetes mellitus and a poor glycemic control presented with fever, loose stools, and loss of appetite of 1 week's duration. An examination was unremarkable apart from a mild non-tender hepatomegaly. Investigations indicated a septic process with neutrophil leukocytosis, thrombocytopenia, and raised inflammatory markers with acute kidney injury. Sonography of his abdomen revealed a large liver abscess with two blood cultures positive for Klebsiella pneumoniae. He made a complete recovery following aspiration of the abscess and treatment with intravenously administered ceftriaxone.. Liver abscess due to Klebsiella pneumoniae is an emerging infection and most commonly reported from Southeast Asia. In Sri Lanka, further studies are necessary to understand the epidemiology and modes of spread. Furthermore, a high index of suspicion is essential as early detection is the key to successful treatment and prevention of complications.

Topics: Anti-Bacterial Agents; Ceftriaxone; Humans; Klebsiella Infections; Klebsiella pneumoniae; Liver Abscess; Male; Middle Aged; Sri Lanka

Spontaneous bacterial peritonitis (SBP) can be life threatening in patients with liver cirrhosis. In contrast to community-acquired SBP, no standard treatment has been established for healthcare-related and nosocomial SBP.. We prospectively collected healthcare-related and nosocomial SBP cases from March 2012 till February 2016 at the Department of Internal Medicine I of the University of Bonn and analysed the prevalence of antibiotic resistance among the isolated bacteria. SBP was diagnosed according to international guidelines. Ciprofloxacin, ceftriaxone and meropenem were used as reference substance for resistance to quinolones, third-generation cephalosporins and carbapenems, respectively.. Ninety-two SBP episodes in 86 patients were identified: 63 episodes (69%) were nosocomial. Escherichia coli, Klebsiella species, enterococci and streptococci were most frequently isolated. Frequencies of these microorganisms were comparable for healthcare-related and nosocomial SBP (14% vs. 11%, 14% vs. 8%, 14% vs. 5% and 10% vs. 6%, respectively). In general, antibiotic resistance was higher in isolates from nosocomial than from healthcare-related SBP (50% vs. 18% for quinolones, 30% vs. 11% for piperacillin-tazobactam; P > 0·05), but comparable concerning third-generation cephalosporins (30% vs. 33%). All microorganisms were sensitive to carbapenems apart from nosocomial infections with Enterococcus faecium (n = 3) and Candida albicans (n = 1) due to intrinsic resistance or lack of microbiological efficacy, respectively. No multidrug-resistant microorganisms were detected. Resistance to initial antibiotic treatment affected 30-day survival negatively (18% vs. 68%; P = 0·002).. Resistance to initial antibiotic treatment was associated with increased mortality. With resistance to cephalosporins being frequent, piperacillin-tazobactam or carbapenems might be preferred as treatment of SBP.

Topics: Aged; Anti-Bacterial Agents; Bacterial Infections; Ceftriaxone; Ciprofloxacin; Cross Infection; Drug Resistance, Bacterial; Enterococcus; Escherichia coli Infections; Female; Gram-Positive Bacterial Infections; Humans; Klebsiella Infections; Liver Cirrhosis; Male; Meropenem; Middle Aged; Peritonitis; Prospective Studies; Streptococcal Infections; Thienamycins

Endophthalmitis is a feared complication of pyogenic liver abscesses caused by hypervirulent Klebsiella pneumoniae strains. First described in East Asia in the 1980s, this invasive syndrome is only recently emerging in Europe and America.. We describe an 84-year-old man who presented to the emergency department with fever, orbital cellulitis, and bilateral visual loss. Although the patient had no overt abdominal symptoms, computed tomography scan revealed a pyogenic liver abscess. Blood cultures were positive for K. pneumoniae. Initial treatment consisted of intravenous ceftriaxone and intravitreal ceftazidime. A unilateral vitrectomy was performed. The patient survived with severe visual sequelae. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: K. pneumoniae pyogenic liver abscess with metastatic endophthalmitis is a relatively new syndrome that should be considered in patients presenting with acute vision loss who appear septic, with or without abdominal complaints. Early recognition prohibits delays in lifesaving treatment.

Topics: Aged, 80 and over; Anti-Bacterial Agents; Ceftriaxone; Emergency Service, Hospital; Endophthalmitis; Fever; Humans; Klebsiella Infections; Klebsiella pneumoniae; Liver Abscess, Pyogenic; Male; Vision Disorders

The objective of this study was to determine whether antibiotic exposure is associated with extended-spectrum-beta-lactamase- or AmpC-producing Escherichia coli or Klebsiella pneumoniae infections in children. We collected extended-spectrum-beta-lactamase- or AmpC-producing E. coli or K. pneumoniae isolates and same-species susceptible controls from normally sterile sites of patients aged ≤21 years, along with associated clinical data, at four free-standing pediatric centers. After controlling for potential confounders, the relative risk of having an extended-spectrum-beta-lactamase-producing isolate rather than a susceptible isolate was 2.2 times higher (95% confidence interval [CI], 1.49 to 3.35) among those with antibiotic exposure in the 30 days prior to infection than in those with no antibiotic exposure. The results were similar when analyses were limited to exposure to third-generation cephalosporins, other broad-spectrum beta-lactams, or trimethoprim-sulfamethoxazole. Conversely, the relative risk of having an AmpC-producing versus a susceptible isolate was not significantly elevated with any antibiotic exposure in the 30 days prior to infection (adjusted relative risk ratio, 1.12; 95% CI, 0.65 to 1.91). However, when examining subgroups of antibiotics, the relative risk of having an AmpC-producing isolate was higher for patients with exposure to third-generation cephalosporins (adjusted relative risk ratio, 4.48; 95% CI, 1.75 to 11.43). Dose-response relationships between antibiotic exposure and extended-spectrum-beta-lactamase-producing or AmpC-producing isolates were not demonstrated. These results reinforce the need to study and implement pediatric antimicrobial stewardship strategies, and they indicate that epidemiological studies of third-generation cephalosporin-resistant E. coli and K. pneumoniae isolates should include resistance mechanisms when possible.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Aztreonam; Bacterial Proteins; beta-Lactamases; Cefepime; Cefotaxime; Ceftazidime; Ceftriaxone; Cephalosporins; Child; Child, Preschool; Drug Resistance, Multiple, Bacterial; Escherichia coli; Escherichia coli Infections; Female; Humans; Infant; Infant, Newborn; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Prospective Studies; Young Adult

Topics: Ceftriaxone; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Laparoscopy; Liver Abscess; Microbial Sensitivity Tests; Middle Aged; Minocycline; Tigecycline

Infection is a major determinant of clinical outcome among patients in the intensive care unit. However, these data are lacking in most developing countries; hence, we set out to describe the profile of nosocomial infection in one of the major tertiary hospitals in northern Nigeria.. Case records of patients who were admitted into the intensive care unit over a 4-year period were retrospectively reviewed. A preformed questionnaire was administered, and data on clinical and microbiological profile of patients with documented infection were obtained.. Eighty-our episodes of nosocomial infections were identified in 76 patients. Road traffic accident (29/76, 38.2%) was the leading cause of admission. The most common infections were skin and soft tissue infections (30/84, 35.7%) followed by urinary tract infection (23/84, 27.4%). The most frequent isolates were Staphylococcus aureus (35/84, 41.7%), Klebsiella pneumoniae (18/84, 21.4%), and Escherichia coli (13/84, 15.5%). High rate of resistance to cloxacillin (19/35, 54.3%) and cotrimoxazole (17/26, 65.4%) was noted among the S aureus isolates. All the Enterobacteriaceae isolates were susceptible to meropenem, whereas resistance rate to ceftriaxone was high (E coli, 55.6%; K pneumoniae, 71.4%; Proteus spp, 50%).. Infection control practice and measures to curtail the emergence of antimicrobial resistance need to be improved.

Topics: Adult; Anti-Bacterial Agents; Bacteremia; Catheter-Related Infections; Ceftriaxone; Cloxacillin; Cross Infection; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Female; Humans; Intensive Care Units; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Nigeria; Pneumonia, Bacterial; Retrospective Studies; Staphylococcal Infections; Staphylococcus aureus; Surgical Wound Infection; Tertiary Care Centers; Thienamycins; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections; Young Adult

Topics: Aged; Anti-Bacterial Agents; Cefotaxime; Ceftriaxone; Diabetes Mellitus; Fermentation; Glucose; Humans; Klebsiella Infections; Klebsiella pneumoniae; Liver; Liver Abscess; Male; Taiwan; Tomography, X-Ray Computed

Klebsiella pneumoniae liver abscess has a tendency to spread to distant sites early in the course of disease and to involve multiple organs synchronously. A 59-year-old male was admitted because of liver abscess accompanied by fever and abdominal pain. The patient underwent percutaneous catheter drainage and received intravenous antibiotics. Symptom relief was achieved after the treatment as well as marked reduction in the size of the abscess. Despite proper treatment of the liver abscess, however, patient developed multiple metastatic infections in a non-concurrent manner: left and right endophthalmitis, psoas abscess, and infectious spondylitis at 5, 23, 30 and 65 days after initial manifestations of liver abscess, respectively. Each infectious episode followed one another after resolution of the former one. For each episode of metastatic infections, the patient promptly underwent treatment with systemic and local antibiotics, interventional abscess drainage, and surgical treatments as needed. The patient fully recovered without sequelae after the use of intravenous antibiotics for an extended period of time. Herein, we report a case of K. pneumoniae liver abscess complicated with delayed-onset multiple metastatic infections.

Topics: Anti-Bacterial Agents; Ceftriaxone; Drainage; Endophthalmitis; Humans; Injections, Intravenous; Klebsiella Infections; Klebsiella pneumoniae; Liver Abscess; Male; Middle Aged; Psoas Abscess; Spondylitis; Tomography, X-Ray Computed

Infections caused by multidrug-resistant pathogens are frequent and life threatening in critically ill patients. To investigate whether severe sepsis affects gut colonization by resistant pathogens and genetic exchange between opportunistic pathogens, we tested the intestinal-colonization ability of an extended-spectrum beta-lactamase-producing Klebsiella pneumoniae strain carrying the SHV-18 resistance gene and the transfer ability of the resistance gene to endogenous Escherichia coli under ceftriaxone treatment in rats with burn injury only or severe sepsis induced by burns plus endotoxin exposure. Without ceftriaxone treatment, the K. pneumoniae strain colonized the intestine in both septic and burned rats for a short time, with clearance occurring earlier in burn-only rats but never in sham burn rats. In both burned and septic rats, the colonization level of the challenge strain dropped at the beginning and then later increased during ceftriaxone treatment, after which it declined gradually. This pattern coincided with the change in resistance of K. pneumoniae to ceftriaxone during and after ceftriaxone treatment. Compared with burn-only injury, severe sepsis had a more significant effect on the change in antimicrobial resistance to ceftriaxone. Only in septic rats was the resistance gene successfully transferred from the challenge strain to endogenous E. coli during ceftriaxone treatment; the gene persisted for at least 4 weeks after ceftriaxone treatment. We concluded that severe sepsis can facilitate intestinal colonization by an exogenous resistant pathogen and the transfer of the resistance gene to a potential endogenous pathogen during antimicrobial treatment.

Topics: Animals; Anti-Bacterial Agents; beta-Lactamases; Burns; Ceftriaxone; Drug Resistance, Multiple, Bacterial; Endotoxins; Escherichia coli; Gene Transfer, Horizontal; Hot Temperature; Intestines; Klebsiella Infections; Klebsiella pneumoniae; Male; Rats; Rats, Sprague-Dawley; Sepsis

Antibiotic resistance in Gram-negative bacteria, especially Enterobacteriaceae, can be conferred by a large number of different acquired resistance genes, although it appears that relatively few dominate. A previous survey of Escherichia coli and Klebsiella pneumoniae isolates from Sydney, Australia, revealed that a limited set of genes could reliably predict resistance to third-generation cephalosporins (3GCs) and aminoglycosides. Here we tested E. coli and K. pneumoniae isolates with a cefotaxime, ceftriaxone and/or ceftazidime minimum inhibitory concentration of ≥ 2 μg/mL from China and Singapore, with significantly higher resistance rates than Australia, as well as the USA. Few targets were needed to predict non-susceptibility to 3GCs (95/95; 100%) and gentamicin (47/51; 92%). The gene types detected here are consistent with previous surveys in similar countries with similar resistance rates, where the majority of 3GC resistance can be explained by blaCTX-M genes. This study identified a limited set of genes capable of predicting resistance to 3GC and aminoglycoside antibiotics and implies a restriction in the global resistance gene pool that can be exploited for diagnostic purposes.

Topics: Anti-Bacterial Agents; Cefotaxime; Ceftazidime; Ceftriaxone; China; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Genes, Bacterial; Gentamicins; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Singapore; United States

Endogenous endophthalmitis is a rare complication of pyogenic liver abscess. It is a devastating intraocular infection which constitutes a vision-threatening emergency. Recently, a significant increase in the incidence of endogenous endophthalmitis associated with pyogenic liver abscess has been reported in East Asia. In this study, the authors investigated the incidence, risk factors, clinical features, and treatment outcomes of endogenous endophthalmitis arising as a complication of pyogenic liver abscess.. The medical records of 8 cases of endogenous endophthalmitis associated with a pyogenic liver abscess treated from 1997 to 2013 at a single tertiary hospital in Korea were retrospectively reviewed.. Median patient age was 71.1 ± 9.8 years. The most common underlying disease was diabetes mellitus (4 patients, 50%). Klebsiella pneumoniae was isolated from all patients, and all were treated with intravenous antibiotics including ceftriaxone. Seven patients received an intravitreal injection. Four patients needed additional surgical interventions. Outcomes were generally poor; only 1 patient achieved a slight improvement in visual outcome.. Old age, diabetes mellitus, and K. pneumoniae infection could predispose the development of endogenous endophthalmitis in patients with a pyogenic liver abscess. Physicians should pay attention to ocular symptoms as early diagnosis and intensive treatment are required to achieve improvements in visual outcome.

Topics: Age Factors; Aged; Aged, 80 and over; Anti-Bacterial Agents; Ceftriaxone; Diabetes Complications; Endophthalmitis; Female; Humans; Imipenem; Incidence; Klebsiella Infections; Klebsiella pneumoniae; Liver Abscess, Pyogenic; Male; Middle Aged; Risk Factors; Treatment Outcome

Topics: Aged; Anti-Bacterial Agents; Arthroplasty, Replacement, Knee; Bacteremia; Ceftriaxone; Cross Infection; Diabetes Mellitus, Type 2; Endocarditis, Bacterial; Female; Gentamicins; Humans; Klebsiella Infections; Klebsiella pneumoniae; Mitral Valve; Prosthesis-Related Infections; Ultrasonography

Topics: Abdominal Abscess; Abdominal Pain; Aged; Anti-Bacterial Agents; Ceftriaxone; Combined Modality Therapy; Drainage; Emphysema; Female; Flank Pain; Gases; Humans; Klebsiella Infections; Pyelonephritis; Radiography, Abdominal; Rupture, Spontaneous; Tomography, X-Ray Computed

Topics: Abscess; Aged; Anti-Bacterial Agents; Ceftriaxone; Coinfection; Combined Modality Therapy; Drainage; Humans; Klebsiella Infections; Klebsiella pneumoniae; Magnetic Resonance Imaging; Male; Peripheral Arterial Disease; Pyomyositis; Quadriceps Muscle; Streptococcal Infections; Viridans Streptococci

Thyroid abscess is a rare condition of the thyroid gland. The common causative organisms responsible for thyroid abscess are Staphylococci and Streptococci species. We described a case of thyroid abscess due to Klebsiella pneumoniae in an infant. The patient was successfully treated with open surgical drainage and appropriate antimicrobial agents.

Topics: Abscess; Anti-Infective Agents; Ceftriaxone; Drainage; Female; Humans; Infant; Klebsiella Infections; Klebsiella pneumoniae; Metronidazole; Thyroid Diseases; Thyroiditis, Suppurative; Treatment Outcome

We describe the first documented case of mycotic aneurysm caused by gas-forming serotype K5, and rmpA and iuc positive Klebsiella pneumonia with a hypermucoviscosity phenotype in a diabetic patient. The patient received ceftriaxone for one month and underwent aorto-bi-iliac grafting and inferior mesenteric artery reimplantation and recovered well.

Topics: Aneurysm, Infected; Anti-Bacterial Agents; Aortic Aneurysm, Abdominal; Bacterial Capsules; Bacterial Proteins; Ceftriaxone; Diabetes Complications; Gases; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Middle Aged; Phenotype; Serotyping; Tomography, X-Ray Computed; Viscosity

Multiresistant, extended spectrum beta lactamase (ESBL)-producing pathogens are an increasing problem in daily clinical life. This paper summarizes the development of resistance as well as epidemiology, diagnostics, and treatment of ESBL-producing micro-organisms. We analyzed microbiological data collected at the Grosshadern Clinic in Germany between 1996 and 2007, in order to assess the importance of these micro-organisms to medical practice and surgical care units.. Pathogens were isolated from 28,894 patients with Escherichia coli and 10,903 with Klebsiella pneumoniae pathogens between 1996 and 2006 and tested for ESBL production. For the year 2007 we have analyzed the complete spectrum of ESBL-producing pathogens and their distribution to different departments of the clinic. The agar diffusion test with five cephalosporins and an automated detection system (BD Phoenix) were used for screening purposes. Positive results were verified with the E- and double-disc agar diffusion tests.. The most important pathogens isolated from patients were E. coli and K. pneumoniae. Analysis of ESBL-producing E. coli pathogens from 1996 to 2006 showed the prevalence increasing from 0% to 4.1%. For ESBL-producing K. pneumoniae, we also found a prevalence rising from 0.3% in 1996 to 6.6% in 2006. For the year 2007 a further increase in ESBL-producing pathogens was detected, reaching 182 cases, with 118 of ESBL-producing E. coli (5.7 %) and 39 of ESBL-producing K. pneumoniae (7.4%). Of these, 24 cases with E. coli and nine with K. pneumoniae were surgery patients (20% and 23%, respectively).. The results show an increasing prevalence of ESBL-producing pathogens in hospitalized patients and in surgical departments. The resulting rise in treatment costs and patient risk require thorough knowledge of risk factors, therapy, and preventive measures.

Topics: Anti-Bacterial Agents; beta-Lactam Resistance; Cefotaxime; Ceftriaxone; Cross Infection; Cross-Sectional Studies; Drug Resistance, Multiple, Bacterial; Escherichia coli Infections; Europe; Humans; Intensive Care Units; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Retrospective Studies; Risk Factors; Surgical Wound Infection

To study risk factors, clinical features, treatment, and visual outcomes in patients with endogenous Klebsiella pneumoniae endophthalmitis (EKE) associated with K. pneumoniae-induced pyogenic liver abscess, and to investigate contributing factors in successfully treated cases.. Retrospective, noncomparative, interventional case series.. Review of medical records of 22 consecutive patients with EKE and pyogenic liver abscess.. The affected eyes of 22 consecutive patients (n = 27) with EKE, who presented to our ophthalmic service during a recent 8-year period, were studied retrospectively.. Best-corrected visual acuity (VA) at end of follow up.. Diabetes mellitus was the most common comorbid risk factor (n = 15 [68%]). Five patients (23%) had bilateral eye involvement. On initial presentation, characteristic pupillary hypopyon was observed in 12 eyes. Diagnosis was confirmed by blood culture in 8 patients, culture of liver aspirate in 17 patients, and vitreous culture in 11 patients. Other associated septic metastatic lesions included pulmonary abscess or emboli in 6 cases, brain abscess or meningitis in 3 cases, and prostate and kidney abscesses in 1 case. Despite aggressive intravenous and intravitreal antibiotic therapy, final VA of light perception or worse affected 24 eyes (89%), of which 11 (41%) were eventually eviscerated or enucleated. Successful treatment with retained useful vision better than 6/60 was achieved in 3 eyes, of which 2 received early intravitreal corticosteroid injections. However, the other remaining eye had a focal subretinal abscess.. Physicians should be alert to the development of EKE when patients with diabetes along with K. pneumoniae-induced pyogenic liver abscess complain of ocular symptoms. In the majority of patients with EKE associated with pyogenic liver abscess, visual outcome is generally poor despite aggressive antibiotic therapy. Early diagnosis and prompt intervention with intravitreal antibiotics within 48 hours may salvage useful vision in some patients with EKE.

Topics: Adult; Aged; Aminoglycosides; Anti-Bacterial Agents; Bacteremia; Ceftriaxone; Diabetes Complications; Drug Therapy, Combination; Endophthalmitis; Eye Enucleation; Eye Infections, Bacterial; Female; Follow-Up Studies; Gallstones; Humans; Klebsiella Infections; Klebsiella pneumoniae; Liver Abscess, Pyogenic; Male; Middle Aged; Retrospective Studies; Risk Factors; Visual Acuity

Topics: Animals; Anti-Bacterial Agents; beta-Lactamases; Ceftriaxone; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Humans; Imipenem; Intestines; Klebsiella Infections; Klebsiella pneumoniae; Mice; Microbial Sensitivity Tests; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination

Klebsiella pneumoniae has long been a prominent cause of nosocomial infections and outbreaks have been observed in the intensive care units and in high risk groups. We present here a brief report on an outbreak of Klebsiella pneumoniae which occurred in a neonatal intensive care unit in our teaching hospital. As neonates are at highest risk for acquisition of Klebsiella pneumoniae producing extended spectrum beta-lactamase, infection control policies and procedures should be strictly followed to prevent such outbreaks.

Topics: Anti-Bacterial Agents; beta-Lactamases; Cefotaxime; Ceftazidime; Ceftriaxone; Cephalosporin Resistance; Cross Infection; Disease Outbreaks; Hospitals, Teaching; Humans; India; Infant, Low Birth Weight; Infant, Newborn; Intensive Care Units, Neonatal; Klebsiella Infections; Klebsiella pneumoniae

Effective methods to control the emergence of extended-spectrum beta -lactamase-producing Escherichia coli and Klebsiella species (ESBL-EK) remain unclear. Variations in the patient populations at different hospitals may influence the effect of antimicrobial formulary interventions.. To examine variations across hospitals in the response to antimicrobial interventions (ie, restriction of ceftazidime and ceftriaxone) designed to curb the spread of ESBL-EK, we conducted a 5-year quasi-experimental study. This study was conducted at 2 hospitals within the same health system: Hospital A is a 625-bed academic medical center, and Hospital B is a 344-bed urban community hospital. All adult patients with a healthcare-acquired clinical culture of ESBL-EK from July 1, 1997 through December 31, 2002 were included.. After the interventions, the use of ceftriaxone decreased by 86% at Hospital A and by 95% at Hospital B, whereas the use of ceftazidime decreased by 95% at Hospital A and by 97% at Hospital B. The prevalence of ESBL-EK at Hospital A decreased by 45% (P < .001), compared with a 22% decrease at Hospital B (P = .36). The following variables were significantly more common among ESBL-EK-infected patients at Hospital B: residence in a long-term care facility (adjusted odds ratio, 3.77 [95% confidence interval, 1.70-8.37]), advanced age (adjusted odds ratio, 1.04 [95% confidence interval, 1.01-1.06]), and presence of a decubitus ulcer (adjusted odds ratio, 4.13 [95% confidence interval, 1.97-8.65]).. The effect of antimicrobial formulary interventions intended to curb emergence of ESBL-EK may differ substantially across institutions, perhaps as a result of differences in patient populations. Variability in the epidemiological profiles of ESBL-EK isolates at different hospitals must be considered when designing interventions to respond to these pathogens.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; beta-Lactamases; Ceftazidime; Ceftriaxone; Enterobacteriaceae; Escherichia coli Infections; Formularies, Hospital as Topic; Humans; Klebsiella Infections; Middle Aged; Population Groups

Topics: Anti-Bacterial Agents; Biopsy, Needle; Ceftriaxone; Cysts; Diagnosis, Differential; Humans; Klebsiella Infections; Klebsiella pneumoniae; Liver Abscess; Liver Diseases; Magnetic Resonance Imaging; Male; Middle Aged; Treatment Outcome

Topics: Abdominal Abscess; Anti-Bacterial Agents; Antitubercular Agents; Ceftriaxone; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Liver Abscess; Male; Middle Aged; Mycobacterium tuberculosis; Splenic Diseases; Tomography, X-Ray Computed; Tuberculosis, Hepatic; Tuberculosis, Splenic

Klebsiella pneumoniae is a common cause of nosocomially acquired pneumonia in immunocompromised patients. Previously, we established a pneumonia model using Klebsiella pneumoniae in B6D2F1/J mice sublethally irradiated with 7-Gy 60Co gamma-radiation and inoculated intratracheally. In the study reported here, we investigated survival of mice following 10 days of antimicrobial therapy with ceftriaxone, gentamicin, gatifloxacin, and a ceftriaxone-gentamicin combination given once daily. Survival was significantly prolonged in response to all therapies. However, survival of mice was 95% when treated with the ceftriaxone-gentamicin combination followed by ceftriaxone alone (75%), and gatifloxacin (80%), whereas survival for controls was 0%. In addition, resistance to any of the treatments did not develop during the study. We conclude that an immunocompromised status does not alter the Infectious Disease Society of America's primary recommendation for treating community-acquired K. pneumoniae pneumonia using a third-generation cephalosporin, with or without an aminoglycoside.

Topics: Animals; Anti-Bacterial Agents; Ceftriaxone; Drug Combinations; Female; Fluoroquinolones; Gatifloxacin; Gentamicins; Humans; Immunocompromised Host; Klebsiella Infections; Klebsiella pneumoniae; Mice; Mice, Inbred Strains; Pneumonia, Bacterial; Survival Rate; Whole-Body Irradiation

Klebsiella oxytoca strains resistant to both aztreonam and ceftriaxone were isolated from six neonates in a neonatal intensive care unit and water reservoirs of two humidifiers attached to the neonatal incubators. These isolates were assumed to be of the same clone because they were characterized by the same antimicrobial susceptibility and pulsed field gel electrophoresis patterns. It was established that the drug resistance was attributed to overproduction of chromosomally encoded Kl beta-lactamase. It was determined that an isolate (K. oxytoca H1) contained a high enzyme concentration (27microg/100microg of protein in enzyme extracts), at least 27 times higher than the control K. oxytoca N1. It was also demonstrated that isolates had a point mutation in the - 35 concensus region of the promotor gene of bla(OXY-2)leading to enzyme overproduction. Outbreaks caused by K1 hyperproducers have not previously been described.

Topics: Aztreonam; Bacterial Proteins; beta-Lactam Resistance; beta-Lactamases; Ceftriaxone; Cross Infection; Electrophoresis, Gel, Pulsed-Field; Humans; Infant, Newborn; Intensive Care Units, Neonatal; Klebsiella; Klebsiella Infections; Microbial Sensitivity Tests; Point Mutation; Polymerase Chain Reaction

This study was explore the distribution of the bacteria and their sensibility to antibiotics in hospital-acquired pneumonia.. One hundred and ninety-six bacterium species were collected in patients with the hospital-acquired pneumonia to make sputum culture. The sensibility of the bacteria to antibiotics were examined by KB paper method and the minimal-inhibitory-concentration by gel double multiple dilute method.. Most of the G- bacteria were pseudomonas aeruginosa (30%) and klebsiella bacillus (22%). Most of the G+ bacteria were staphylococcus epidermidis (14%) and staphylococcus aureus (12%). G- bacteria were sensitive to impienem(98%), cefoperazone(90%), ceftriaxone(90%), leftazidime(92%), ciprofloxacin(90%), and amikacin(89%). The sensibility of vancomycin to G+ bacteria was 100%.. The pseudomonas aeruginosa, klebsiella bacillus, staphylococcus epidermidis, and staphylococcus aureus are the most important bacteria in patients with hospital-acquired pneumonia. Imipenem, cefoperazone, ceftriazone, leftazidime, ciprofloxacin, amikacin, and vancomycin are effective antibiotics for treating hospital-acquired pneumonia.

Topics: Adult; Aged; Aged, 80 and over; Cefoperazone; Ceftriaxone; Cross Infection; Female; Humans; Imipenem; Klebsiella Infections; Klebsiella pneumoniae; Male; Middle Aged; Pneumonia, Bacterial; Pseudomonas aeruginosa; Pseudomonas Infections; Staphylococcal Infections; Staphylococcus epidermidis

A prospective study conducted among Jordanian ICU patients in 1997 using Etest identified resistance rates among isolates of E. coli (25%-44%), Enterobacter spp. (54%-62%), and Klebsiella spp. (30%-80%) to extended-spectrum B-lactams (ESBLs): ceftazidime, cefotaxime, ceftriaxone, and aztreonam. All these isolates were susceptible to imipenem and showed low resistance rate to ciprofloxacin (5%-19%) and amikacin (13%-18%). Higher and significant resistance rates of Klebsiella isolates to ceftazidime (80%) and aztreonam (65%) were observed in 1997 compared with a previous study performed in 1994. The majority of Klebsiella pneumoniae (70%) express different ESBL phenotypes that were almost resistant to aztreonam and ceftazidime but susceptible or resistant to cefotaxime and/or ceftriaxone. This prospective study strongly suggests that ESBL production of Klebsiella pneumoniae isolates have been highly disseminated among ICU patients during 1997.

Topics: Aztreonam; beta-Lactam Resistance; Cefotaxime; Ceftazidime; Ceftriaxone; Cross Infection; Gram-Negative Bacteria; Humans; Incidence; Intensive Care Units; Jordan; Klebsiella Infections; Klebsiella pneumoniae; Lactams; Microbial Sensitivity Tests; Prospective Studies; Sensitivity and Specificity

Fifty-two strains of Klebsiella pneumoniae producing an AmpC-type plasmid-mediated beta-lactamase were isolated from 13 patients in the same intensive care unit between March 1998 and February 1999. These strains were resistant to ceftazidime, cefotaxime and ceftriaxone, but susceptible to cefoxitin, cefepime and aztreonam. Plasmid content and genomic DNA restriction pattern analysis suggested dissemination of a single clone. Two beta-lactamases were identified, TEM-1 and ACC-1. We used internal bla(ACC-1) primers, to sequence PCR products obtained from two unrelated strains of Hafnia alvei. Our results show that the ACC-1 beta-lactamase was derived from the chromosome-encoded AmpC-type enzyme of H. alvei.

Topics: Amino Acid Sequence; Aztreonam; Bacterial Proteins; Base Sequence; beta-Lactamases; Cefepime; Cefotaxime; Cefoxitin; Ceftazidime; Ceftriaxone; Cephalosporins; Cephamycins; Cloning, Molecular; Cross Infection; Disease Outbreaks; Drug Resistance, Microbial; Electrophoresis, Gel, Pulsed-Field; France; Hafnia; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Molecular Sequence Data; Monobactams; Plasmids; Polymerase Chain Reaction

Forty patients with spontaneous bacterial peritonitis, three of whom had complicating acute hepatitis syndrome, eight late-onset hepatic failure, and 29 with cirrhosis, were treated with ceftriaxone 2 g intravenously once daily for 5 days. Ascitic fluid culture was positive in 28 patients, with Escherichia coli and Klebsiella as common isolates. All the bacteria isolated were sensitive to ceftriaxone except Enterococcus faecalis, which was isolated in a cirrhotic patient. All culture-positive patients sensitive to ceftriaxone showed bacteriological cure and 26 (65%) patients showed cytological cure after 48 hours of treatment. A total of 95% were cured of their infection after 5 days of treatment. Twelve (30%) patients died during hospitalisation after documented cure of their spontaneous bacterial peritonitis (renal failure, gastrointestinal bleed and cerebral oedema were the primary causes of death). Infection-related mortality due to Pseudomonas septicaemia was seen in one cirrhotic patient.

Topics: Adolescent; Adult; Ceftriaxone; Cephalosporins; Escherichia coli Infections; Female; Humans; Klebsiella Infections; Liver Diseases; Male; Middle Aged; Peritonitis; Prospective Studies

The effect of cytostatic treatment on the cellular defence and the efficacy of treatment with ceftriaxone in Klebsiella pneumoniae pneumonia was studied. Mice, made monocytopenic and granulocytopenic by cyclophosphamide or monocytopenic by etoposide, were infected intratracheally with K. pneumoniae (approximately 10(4) CFU) and then treated with ceftriaxone. At various intervals, the numbers of bacteria in the broncho-alveolar lavage (BAL) fluid and in lungs homogenised after lavage were determined. Cyclophosphamide reduced the numbers of granulocytes in the BAL fluid significantly but reduced only slightly the number of alveolar macrophages at the time of inoculation, 12 and 15 h later. The number of CFU in cyclophosphamide-treated mice was higher than that in controls, being significant in the homogenised lungs at 15 h after infection. In etoposide-treated mice, the numbers of alveolar phagocytes in BAL did not differ from those in control mice, whereas the number of bacteria was lower (only significantly in BAL fluid at 15 h after infection) than that in the controls. In this short experimental infection cytostatic treatment did not affect the outgrowth of Klebsiella pneumoniae substantially or the efficacy of treatment with ceftriaxone.

Topics: Animals; Antineoplastic Agents; Bronchoalveolar Lavage Fluid; Ceftriaxone; Cyclophosphamide; Disease Models, Animal; Etoposide; Granulocytes; Immunosuppressive Agents; Klebsiella Infections; Klebsiella pneumoniae; Leukopenia; Lung Diseases; Macrophages, Alveolar; Male; Mice; Phagocytosis; Specific Pathogen-Free Organisms

The in vitro activity of cefodizime and two comparative cephalosporins, cefuroxime and ceftriaxone were studied against respiratory pathogens. MIC90s of cefodizime were 0.06-0.512 microgram/ml for Streptococcus pneumoniae, Moraxella catarrhalis and Haemophilus influenzae. MIC50s of cefodizime for Klebsiella pneumoniae and Staphylococcus aureus isolates were 2 micrograms/ml and 8 micrograms/ml respectively. Cefuroxime and ceftriaxone at a concentration of 2 micrograms/ml and 1 microgram/ml inhibited 50% of Klebsiella pneumoniae and 50% of Staphylococcus aureus strains studied respectively. Cefodizime inhibited many of the important respiratory pathogens and can be suggested as an active antimicrobial agent for respiratory tract infections.

Topics: Cefotaxime; Ceftriaxone; Cefuroxime; Haemophilus Infections; Haemophilus influenzae; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Moraxella catarrhalis; Neisseriaceae Infections; Pneumococcal Infections; Respiratory Tract Infections; Staphylococcal Infections; Staphylococcus aureus; Streptococcus pneumoniae

Mice made monocytopenic and granulocytopenic by cyclophosphamide or monocytopenic by etoposide were infected by exposure to an aerosol containing Klebsiella pneumoniae. Eighteen hours later ceftriaxone was administered and three hours after that the experiment was ended. At the time of infection and at 18 and 21 h the numbers of alveolar macrophages and granulocytes in bronchoalveolar lavage (BAL) fluid were significantly lower in the cyclophosphamide-pretreated animals than in the controls. Furthermore, outgrowth of K. pneumoniae in the lungs was significantly stronger in cyclophosphamide-pretreated mice and a fourfold higher dose of ceftriaxone was needed to obtain the same antibacterial effect as in the controls. In the etoposide-pretreated mice the number of alveolar macrophages in BAL was not significantly lower than that in the controls, but the number of granulocytes was. Compared with the controls, there was no significant difference in the number of K. pneumoniae in the lungs, and the efficacy of ceftriaxone did not differ either.

Topics: Animals; Bronchoalveolar Lavage Fluid; Ceftriaxone; Cell Count; Cyclophosphamide; Disease Models, Animal; Dose-Response Relationship, Drug; Etoposide; Klebsiella Infections; Klebsiella pneumoniae; Lung Diseases; Male; Mice; Phagocytes; Pulmonary Alveoli

We studied the activity of the combination of sulbactam and ceftriaxone against a Klebsiella pneumoniae strain producing TEM-3, a new extended-broad-spectrum beta-lactamase, in an endocarditis model. In vitro, ceftriaxone was strongly inactivated in the presence of TEM-3 (MBC, 128 micrograms/ml with an inoculum of 5 x 10(5) CFU/ml). A marked inoculum effect was demonstrated with sulbactam: effective concentrations of inhibitor needed to reduce the MIC and MBC of ceftriaxone to similar levels increased from 1 microgram/ml in the presence of an inoculum of 5 x 10(5) CFU/ml to 20 micrograms/ml in the presence of an inoculum of 1 x 10(7) CFU/ml. In vivo, sulbactam given at 200 mg/kg of body weight every 12 h, a dosage higher than that previously reported to be effective against rabbit endocarditis caused by other microorganisms, was not sufficient to restore the complete activity of ceftriaxone given at 30 mg/kg once daily for 4 days. This insufficient activity may be correlated with the presence of a high level of beta-lactamase inside the vegetations, as indicated by a quantitative in vitro assay of beta-lactamase activity in the cardiac vegetation, suggesting an insufficient inactivation of the extended-broad-spectrum beta-lactamase in vivo.

Topics: Animals; beta-Lactamases; Ceftriaxone; Drug Resistance, Microbial; Drug Therapy, Combination; Endocarditis, Bacterial; Female; Half-Life; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Rabbits; Sulbactam

The in vitro activity of four cephalosporins was compared with their effects in an experimental thigh infection (cefuroxime and cefamandole against Escherichia coli and cefamandole, ceftriaxone, and ceftazidime against Klebsiella pneumoniae) in granulocytopenic mice. The effect in vitro (ER) was defined as the difference between the growth rate without antibiotic and the growth rate at the steepest part of a 3-h growth curve in the presence of an antibiotic. The relation between concentration and ER was described with the Hill equation. Using pharmacokinetic parameters of the plasma concentrations in vivo and those of the Hill equation the corresponding time course of ER was calculated and by integration with respect to time (0tERdt), an estimate was obtained of the effect on bacteria. For all four antibiotics this estimate was significantly correlated with the actual values of the effect in vivo (EN), defined as the difference in numbers of bacteria between controls and antibiotic-treated animals at 4 h.

Topics: Agranulocytosis; Animals; Cefamandole; Ceftazidime; Ceftriaxone; Cefuroxime; Cephalosporins; Disease Models, Animal; Escherichia coli; Escherichia coli Infections; Klebsiella Infections; Klebsiella pneumoniae; Mice; Protein Binding; Specific Pathogen-Free Organisms

The effects of monocytopenia and granulocytopenia on the proliferation of Klebsiella pneumoniae and the efficacy of treatment with ceftriaxone were studied in an experimental lung infection in mice. Treatment with etoposide led to monocytopenia, and cyclophosphamide to granulocytopenia and monocytopenia. Both drugs gave a decrease in the number of alveolar macrophages during the infection and a diminished influx of granulocytes into the alveolar space. The mice treated with etoposide did not differ from controls with respect to either the proliferation of Kl. pneumoniae during the infection or the antibiotic efficacy of ceftriaxone. In cyclophosphamide-treated mice the proliferation rate of Kl. pneumoniae was higher than that in the control mice and a higher dose of ceftriaxone was needed to reduce the number of bacteria to the level in the controls. From these findings it is concluded that granulocytes play an important role in the numerical reduction of Kl. pneumoniae and that monocytes make no contribution to infection control in this model.

Topics: Agranulocytosis; Animals; Ceftriaxone; Cyclophosphamide; Etoposide; Klebsiella Infections; Klebsiella pneumoniae; Lung Diseases; Mice; Monocytes

Endophthalmitis is a well-recognized complication of intraocular surgery, penetrating ocular trauma and systemic infection. Metastatic bacterial endophthalmitis is rare. However, once it happens, the visual outcome is very poor. In order to prevent visual damage, early diagnosis and treatment is essential. Due to the blood-ocular barrier, intravitreal drug concentrations are low after systemic administration. Strong antibiotics with good penetration into the vitrous humor are needed to obtain adequate bactericidal concentrations. We report two cases with liver abscess complicated by septic events to the eye. One was uveitis, and the other was endophthalmitis. They were diagnosed early and were successfully treated with parenteral ceftriaxone and good vision was preserved.

Topics: Adult; Ceftriaxone; Endophthalmitis; Enterobacteriaceae Infections; Fluorescein Angiography; Humans; Klebsiella Infections; Liver Abscess; Male; Middle Aged; Sepsis; Sulfamethoxazole; Trimethoprim; Ultrasonography; Uveitis; Visual Acuity

The bactericidal quotient (BQ) assessed in the site of infection represents an essential parameter for evaluating the real bactericidal potency of an antibiotic in vivo. The assessment and knowledge of BQ values allow us to set up a more accurate and appropriate antibacterial therapy. The two drugs--ceftriaxone (Rocephin) and imipenem plus cilastatin (Tienam)--that have been taken into consideration in this study, having a similar antibacterial spectrum though with different kinetics, may have the same BQ values in bronchial secretion versus Haemophilus influenzae, Klebsiella pneumoniae and Streptococcus pneumoniae, when administered at different dosages, i.e. ceftriaxone 1 g (i.v.) every 24 h, imipenem 0.5 g (i.v.) every 8 h.

Topics: Aged; Bronchial Diseases; Ceftriaxone; Cilastatin; Drug Administration Schedule; Drug Combinations; Haemophilus Infections; Haemophilus influenzae; Humans; Imipenem; Klebsiella Infections; Klebsiella pneumoniae; Middle Aged; Sputum; Streptococcal Infections; Streptococcus pneumoniae

The ability of antibiotic combinations to limit the emergence of resistance during therapy was evaluated in a murine model. Peritonitis was produced by injecting a mixture containing 10(8) colony-forming units of bacteria and sterilized talcum into the peritoneum. Two hours later, a single antibiotic dose was administered subcutaneously. The next day, peritoneal bacterial populations were analyzed on Szybalski's gradients. Acquired resistance was recorded when there was at least a fourfold increase in minimum inhibitory concentrations compared with untreated animals. No resistance emerged after amikacin monotherapy (15 mg/kg); however, resistance was frequently observed after monotherapy with ceftriaxone (50 mg/kg) or pefloxacin (25 mg/kg). Resistance to ceftriaxone and pefloxacin emerged, respectively, in 15 percent and 83 percent of animals with Klebsiella pneumoniae, 71 percent and 54 percent with Enterobacter cloacae, 0 percent and 83 percent with Serratia marcescens, 25 percent and 100 percent with Pseudomonas aeruginosa, and 0 percent with both Escherichia coli and Staphylococcus aureus. In mice with K. pneumoniae or E. cloacae infections, any dual combination of amikacin, pefloxacin, and ceftriaxone produced less acquired resistance than did monotherapy. In these animals, the combination of ceftriaxone and pefloxacin abolished all resistance, whereas the combinations of amikacin plus ceftriaxone or amikacin plus pefloxacin reduced the frequency of resistance by more than half. In animals with P. aeruginosa or S. marcescens infections, resistance to pefloxacin diminished or disappeared after treatment with the combinations of pefloxacin plus ceftriaxone or pefloxacin plus amikacin. However, combinations with ceftriaxone resulted in more frequent resistance to ceftriaxone than did ceftriaxone alone. This was the case in P. aeruginosa infections treated with ceftriaxone plus amikacin (p less than 0.01), and in S. marcescens infections treated with ceftriaxone plus pefloxacin (p less than 0.05). Despite these certain notable exceptions, our data confirm that in most cases combination therapy does limit the emergence of resistance.

Topics: Amikacin; Animals; Anti-Bacterial Agents; Ceftriaxone; Drug Resistance, Microbial; Drug Therapy, Combination; Enterobacter; Enterobacteriaceae Infections; Escherichia coli; Escherichia coli Infections; Female; Klebsiella Infections; Klebsiella pneumoniae; Mice; Mice, Inbred ICR; Norfloxacin; Pefloxacin; Pseudomonas aeruginosa; Pseudomonas Infections; Serratia marcescens; Staphylococcal Infections; Staphylococcus aureus; Time Factors

The therapeutic efficacy of ceftriaxone and gentamicin was investigated in a foreign body induced abscess model in the rat by implanting a dialysis tube contaminated with Klebsiella pneumoniae into the subcutaneous tissue. Animals were treated for four days with ceftriaxone, gentamicin, and their combination starting immediately following or 48 h after the implantation. Peak free ceftriaxone and gentamicin abscess fluid levels were 4.3 and 2.6 mcg/ml, which were 7.3% and 37.5% of peak blood levels respectively. Both agents persisted longer in abscess fluid than in blood. Ceftriaxone inhibited the development of abscess formation when administered shortly after the implantation of the contaminated foreign body whereas gentamicin alone was without beneficial effect. When administered after 48 h ceftriaxone was less effective than immediately after implantation and gentamicin was again without any therapeutic effect. The effect of the combination of ceftriaxone and gentamicin was slightly better than ceftriaxone alone. Low oxygen tension may be an explanation for the lack of bactericidal effect of gentamicin. Ceftriaxone may be more suitable for the therapy of closed space infections caused by susceptible microorganisms than gentamicin.

Topics: Abscess; Animals; Cefotaxime; Ceftriaxone; Disease Models, Animal; Drug Evaluation, Preclinical; Drug Therapy, Combination; Female; Gentamicins; Kinetics; Klebsiella Infections; Klebsiella pneumoniae; Male; Rats; Rats, Inbred Strains