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PubMed2006

Pharmacokinetic study of pleural fluid penetration of carbapenem antibiotic agents in chemical pleurisy.

STUDY OBJECTIVES: We investigated pleural fluid penetration of carbapenem antibiotic agents [imipenem (IPM), panipenem (PAPM), meropenem (MEPM), and biapenem (BIPM)] using an experimental rabbit pleuritis model to clarify the usefulness of the carbapenem agents for the treatment of bacterial pleurisy or pyothorax. MEASUREMENTS AND RESULTS: Serum and pleural fluid specimens were serially collected at 5, 10, 15, 30, 60, 90, 120, 180, 240, 300, and 360 min after antibiotic administration for measurement of antibiotic levels. We investigated each agent alone as well as drug solutions containing each agent and a dehydropeptidase-I-specific inhibitor, cilastatin (CS), to remove the influence of dehydropeptidase-I-related hydrolysis. Groups of animals (n=3) received each carbapenem agent with or without CS. Serum and pleural fluid antibiotic levels were measured by high-performance liquid chromatography (HPLC). Because Cmax is not useful for evaluating the antimicrobial effects of carbapenem antibiotic agents due to their dose-dependent antimicrobial activity, we also investigated the AUC, which is correlated with the total drug levels in vivo. Among the drug solutions containing CS, MEPM/CS had the highest pleural fluid AUC0-360 (1594.8+/-510.3 microg min/ml), and the highest pleural fluid AUC0-360/plasma AUC0-360 ratio (0.79+/-0.04). BIPM/CS had the highest plasma AUC0-360 (3040.1+/-1525.9 microg min/ml). In pleural fluid AUC0-360/plasma AUC0-360 ratio MEPM/CS was significantly higher than those for the remaining agents. In pleural fluid AUC0-360 and plasma AUC0-360 there were no significant differences among these mixed solutions. CONCLUSIONS: MEPM had the most favorable pleural fluid penetration. Pleural fluid penetration should be examined in infection models and in clinical trials.

Animals↗

PubMed2005

Factors in association with sepsis after liver transplantation: the Hungarian experience.

Sepsis is the major cause of patient death after orthotopic liver transplantation (OLT). To identify risk factors for sepsis, we analyzed all 199 primary OLTs performed between 1995 and 2004. Patients were divided into 2 groups according to whether they experienced sepsis after liver transplantation. Recipient, perioperative factors, and complications were subjected to univariate analyses. Statistically significant factors were exposed to multivariate analyses: Cox regression and Hosmer-Lemeshow test. Sepsis occurred in 45 (23%) patients. Recipient Child-Pugh score, preoperative broad spectrum antibiotic (meropenem) prophylaxis, intraoperative red blood cell transfusion, starch infusion, postoperative bleeding, hepatic artery thrombosis, and biliary leakage/necrosis were independent risk factors for sepsis. Our results agree with the international experience. A high amount of starch infusion and an extended use of broad spectrum antibiotics for prophylaxis adverse experiences in our center and have been removed from the protocol.

Analysis of Variance↗

PubMedDate not supplied

Biliary liver cirrhosis secondary to cystic fibrosis: a rare indication for liver transplantation.

As more effective therapies prolong the lives of patients with cystic fibrosis, there are now more patients in this population diagnosed with liver diseases. Secondary biliary cirrhosis is not a rare complication of mucoviscidosis. It is diagnosed in 20% of patients with mucoviscidosis; in 2% it is accompanied by portal hypertension. On average patients with portal hypertension and its complications are 12 years old. Liver transplantation is an accepted method of treatment for children with cystic fibrosis and portal hypertension. It eliminates the cause of the portal hypertension, decreases life-threatening medical conditions, and improves their nutritional status and quality of life. Despite immunosuppressive treatment they do not seem to beat increased risk of upper respiratory tract infections. On the contrary improved respiratory function and status are generally observed. We present our first case of orthotopic liver transplantation performed in a 29-year-old man with cystic fibrosis. The donor was a 42-year-old woman who died of a ruptured cerebral aneurysm. The surgery was performed in September 2004. The patient received immunosuppression based on steroids, basiliximab, tacrolimus, and mycophenolic acid due to renal insufficiency. Antibiotic (meropenem) and antiviral prophylaxis (gancyclovir) were used. A 6-month period of observation confirmed the clinical data from the pediatric population-a good prognosis with improved nutritional status, respiratory function, and quality of life.

Adult↗

PubMed2006

Infectious complications after multivisceral transplantation in adults.

UNLABELLED: It is thought that multivisceral transplantation requires high levels of immunosuppression and therefore, patients run an increased risk of infection. We retrospectively reviewed our center's experience with clinically relevant infectious complications. PATIENTS: Between 2000 and 2005, 10 adult patients underwent multivisceral transplantation. Two immunosuppression protocols were used: between 2000 and 2003, a high immunosupression protocol (six patients; daclizumab induction, tacrolimus trough levels >20 ng/mL and steroids) and an immunomodulatory, low imunosuppression scheme from 2003 onward (four patients; ATG induction, tacrolimus levels 5 to 10 ng/mL, no steroids). Standard antimicrobial prophylaxis consisted of vancomycin, meropenem, and amphotericin B. Cytomegalovirus (CMV) prophylaxis was used in all but first two cases. Donor and recipient CMV status were D+/R+ (n = 7), D+/R- (n = 2), D-/R+ (n = 1). RESULTS: The median follow-up period was 627 days (range, 19 to 2207 days). A total of 47 infectious episodes were recorded in all patients (range 1 to 14 per patient). The etiology was bacterial in 32 (69%), viral in 8 (17%), and fungal in 7 (14%) cases. The most frequent were catheter related (n = 13) followed by respiratory (n = 7), intraabdominal (n = 6), and wound infections (n = 5). Symptomatic viral infection of the graft (CMV gastritis or enteritis, adenoviral enteritis) was also encountered. Epstein-Barr virus was transiently detected in the serum of nine patients, one of whom later developed posttransplant lymphoproliferative disorder (PTLD). Three deaths all among patients receiving high immunosuppression were owing to infectious complications: pulmonary PTLD at 4 months posttransplantation, ruptured mycotic aneurysm after 8 weeks, and sepsis after 3 weeks. CONCLUSIONS: Infections accounted for a high morbidity after multivisceral transplantation, representing the leading cause of mortality. Exhaustive monitoring, early antimicrobial intervention, and lower immunosuppression may improve the outcome.

Adult↗

PubMed2001

A novel metallo-beta-lactamase, Mbl1b, produced by the environmental bacterium Caulobacter crescentus.

Caulobacter crescentus 101123 possesses a gene (Mbl1b) encoding a metallo-beta-lactamase with 32% amino acid identity to the L1 metallo-beta-lactamase from Stenotrophomonas maltophilia. The gene was cloned into an expression vector and the enzyme, Mbl1b, was expressed in Escherichia coli. Mbl1b was purified. Catalytic properties for several antibiotics were determined. The enzyme exhibits Michaelis-Menten kinetics for imipenem, meropenem and nitrocefin but substrate inhibition kinetics with cefoxitin, cefaloridine, penicillin G and ampicillin. A homology model predicts Mbl1b has the same structural fold as other metallo-beta-lactamases with a detailed structure very similar to L1 but whereas L1 is a homotetramer, Mbl1b is monomeric. The main differences between Mbl1 and L1 are in the N-terminal region.

Amino Acid Sequence↗

PubMedDate not supplied

Melioidosis: acute and chronic disease, relapse and re-activation.

In melioidosis-endemic regions the importance of re-activation of Burkholderia pseudomallei from latent foci remains unclear. This topic was assessed in a 10-year prospective study (1989-99) of melioidosis in the tropical north of the Northern Territory of Australia, together with other aspects of the nature of melioidosis. Incubation period from defined inoculating events was previously ascertained as 1-21 (mean 9) days. Of 252 total cases 244 (97%) were considered to be from recent acquisition of B. pseudomallei infection and 8 (3%) were considered to be re-activation from a latent focus. Acute illness occurred in 222 (88%) cases; 30 (12%) cases had chronic illness (symptomatic for > 2 months). Of the 207 patients surviving the initial illness, 27 (13%) had a confirmed relapse (mean time from initial diagnosis of 8 months), with 5 relapsing twice. Of these 32 relapses, 15 (3 fatal) were associated with poor adherence to the eradication therapy antibiotics and 10 (none fatal) were failures of eradication with doxycycline monotherapy. Following initial intensive therapy with ceftazidime or meropenem for at least 14 days, eradication therapy with trimethoprim-sulphamethoxazole monotherapy for at least 3 months had been more successful.

Acute Disease↗

PubMedDate not supplied

A proposed scoring system for predicting mortality in melioidosis.

Melioidosis, due to infection with the environmental organism Burkholderia pseudomallei, continues to be associated with high mortality despite improvements in antibiotic therapy. Using simple clinical findings and baseline laboratory tests available at the time of admission, we attempted to define those patients with acute melioidosis who were at higher risk of death. Using data, collected prospectively from the period October 1989 to June 2002, from patients with acute culture-confirmed melioidosis presenting at the Royal Darwin Hospital, Darwin, Australia, a number of variables were selected that were easily available at the time of admission and reflected organ dysfunction. Mortality was predicted in univariate logistic and multivariate models by the presence of pneumonia, age at diagnosis, serum urea, serum bilirubin, lymphocyte count, and serum bicarbonate. A score was assigned from 0 to 2, based on the degree of abnormality. A melioidosis score was formed from the sum of these scores, with a maximum score of 11. A score of < or = 3 (n = 140) was associated with a mortality of 8.6%, whereas a score of > or = 4 (n = 112) was associated with a mortality of 44.6%. Although this scoring system requires external validation, it may help identify a suitable target group of patients for intensive intervention such as early admission to an intensive care unit, the early use of meropenem, and goal-directed resuscitation therapies.

Female↗

PubMed2003

Antibiotic resistance patterns of ocular bacterial flora: a prospective study of patients undergoing anterior segment surgery.

PURPOSE: To determine the antibiotic susceptibility patterns of conjunctival bacterial flora isolated preoperatively from patients undergoing anterior segment surgery. DESIGN: Prospective observational study. PARTICIPANTS: One hundred fifty-six eyes from 139 patients scheduled for anterior segment surgery were enrolled over a 6-month period from August 2001 to February 2002. METHODS: Conjunctival cultures were obtained on the day of surgery before povidone-iodine or antibiotic application. MAIN OUTCOME MEASURES: Bacterial isolates were identified and tested for antibiotic susceptibility using the Kirby-Bauer disc-diffusion technique. RESULTS: Among the 156 eyes studied, 36 were from patients who had undergone either bilateral surgery or more than one surgery in the same eye. Only the first eyes of the 120 patients that underwent initial ocular surgery were included in our analysis. Of these 120 eyes, 21 (18%) showed no bacterial growth. Of the 143 bacterial strains isolated from the remaining 99 eyes, 112 (78%) were coagulase-negative staphylococci (CNS). Among the CNS, greater than 90% were susceptible to cefotaxime, levofloxacin, imipenem, meropenem, vancomycin, and each of the aminoglycosides except neomycin. Between 70% and 90% of the CNS were susceptible to cefazolin, neomycin, ciprofloxacin, ofloxacin, norfloxacin, and chloramphenicol. Less than 70% of the isolated CNS were sensitive to the penicillin analogues, ceftazidime, erythromycin, and tetracycline. CONCLUSIONS: Preoperative conjunctival isolates of CNS seem to be most sensitive to vancomycin, the aminoglycosides (except neomycin), and levofloxacin.

Aged↗

PubMedDate not supplied

Epidemiologic Study of Pseudomonas aeruginosa in critical patients and reservoirs.

BACKGROUND: Pseudomonas aeruginosa is a common cause of nosocomial infections, particularly in intensive care units (ICUs). The aim of this study was to characterize P. aeruginosa clinical isolates by comparing antimicrobial susceptibility patterns with the presence of plasmids and to establish the clonal relatedness by pulsed-field gel electrophoresis (PFGE) typing. METHODS: The patients included those with isolation of P. aeruginosa hospitalized for more than 48 h in the ICU from April to May 1998. Environmental and staff cultures were obtained simultaneously. Minimal inhibitory concentrations, plasmid DNA profiles, and PFGE genomic patterns of enzyme restriction chromosomal DNA were compared. RESULTS: Sixty P. aeruginosa isolates were obtained from 197 clinical specimens, 178 environmental samples, and 47 hand cultures of personnel. Antimicrobial resistance was as follows: tobramycin 100%; ticarcillin, cefotaxime, ceftriaxone, ceftazidime, and gentamicin 80%; cefepime 60%; amikacin, ticarcillin/clavulanate, imipenem, and meropenem 40%; piperacillin and norfloxacin 20%; carbenicillin 12%, and ciprofloxacin 0%. Plasmids were detected in 11 isolates (18%). PFGE typing showed that 23 isolates belonged to a common clone (pattern A), identified from five patients, two nurses, and 10 environmental samples. Ten isolates were grouped in four clusters and 27 isolates had unrelated genomic patterns. There was no relationship among DNA genomic patterns, plasmid profiles, and susceptibility patterns. CONCLUSIONS: PFGE demonstrated the existence of a common clone in a critical care area. Reinforcement of infection control measures is needed to avoid horizontal transmission and severe infections.

Critical Illness↗

PubMed2002

Primary brain abscess with Nocardia farcinica in an immunocompetent patient.

In this paper, we describe a case of an immunocompetent patient with cerebral nocardiosis. The onset was with loss of strength, paresthesia and focal epilepsy of the left arm. MRI showed on T2-weighted sequences a hyperintense central area of pus surrounded by a well-defined hypointense capsule and surrounding edema; on T1-weighted sequences a hypointense necrotic cavity with ring enhancement following administration of intravenous gadolinium. The patient underwent surgical excision of the abscess but culture from the specimen was negative. After 40 days of empirical antimicrobial therapy he developed neurological deterioration with focal epilepsy. A new MRI documented an enlargement of the hypointense lesion in the right frontal-parietal region. A second craniotomy with drainage of the abscess was performed; cultures yielded Nocardia farcinica. Therapy with trimethoprim/sulfamethoxazole, amikacin and meropenem was given for 35 days, and clinical and radiological improvement was observed. Home therapy was done with oral trimethoprim/sulfamethoxazole. Currently, 5 months from the second surgery, the patient can walk with support and no new episodes of epilepsy occurred. Side effects were absent from therapy. The MRI appearance of the brain lesion has improved, with a decrease in size, surrounding edema and ring enhancement.

Brain Abscess↗

PubMed2003

In vitro activity of ertapenem against anaerobes isolated from the respiratory tract.

Ertapenem is a novel parenteral carbapenem with a long serum half-life. Its spectrum of activity is similar to that of imipenem and meropenem against Gram-positive bacteria, Enterobacteriaceae and fastidious Gram-negative bacteria but it is less active against Pseudomonas aeruginosa and Acinetobacter spp. Several studies were performed in the United States but only one European study has shown that ertapenem has an excellent activity against anaerobes. The objectives of the present study were to test the activity of ertapenem against anaerobes isolated prospectively from the lower and upper respiratory tracts, and to compare their susceptibility with that of anaerobic isolates from other body sites. Fifty-three isolates from the respiratory tract, as well as 50 isolates from various other body sites were tested with E-tests against six antibiotics. For respiratory isolates and for isolates from other sites, MIC 90 values (mg/l) were, respectively, >32 and >32 for penicillin, 0.38 and 0.75 for amoxicillin/clavulanate, 48 and >256 for ceftriaxone, 0.12 and 0.75 for ertapenem, 12 and >256 for clindamycin and 2 and 12 for moxifloxacin. The higher susceptibility of respiratory tract isolates was mainly due to the different distribution of isolated species: only three respiratory isolates but 22 other isolates belonged to the Bacteroides fragilis group. This study confirms the excellent anti-anaerobic activity of ertapenem against anaerobic isolates from the respiratory tract.

Bacteria, Anaerobic↗

PubMed1999

Simple and rapid analytical method for carbapenems using capillary zone electrophoresis.

A simple and rapid analytical method for carbapenems using high-performance capillary electrophoresis is described. All therapeutic carbapenem injections in Japan (imipenem, panipenem and meropenem) and four other beta-lactams (piperacillin, cefotiam, cefotaxime, latamoxef) were separated and determined with good repeatability in about 10 min using simple free zone capillary electrophoresis. The electrophoresis buffer was 100 mM phosphate buffer of pH 8.0, and a fused-silica capillary of 25 microm I.D. and 47 cm length was adopted. The present method was successfully applied to monitor the degradation of carbapenems under various conditions (at various temperatures or in coexistence with other drugs prescribed in the case of methicillin-resistant Staphylococcus aureus).

Anti-Bacterial Agents↗

PubMed2000

Antimicrobial susceptibility of Abiotrophia adiacens and Abiotrophia defectiva.

The susceptibilities of 27 Abiotrophia adiacens (proposed reclassification Granulicatella adiacens comb.nov., Collins & Lawson, 2000) and 12 Abiotrophia defectiva isolates were tested by microdilution in pyridoxal hydrochloride and lysed horse blood supplemented Mueller-Hinton broth. According to NCCLS interpretative criteria for Streptococcus spp. not Streptococcus pneumoniae, the susceptibilities of A. adiacens and A. defectiva were, respectively: penicillin, 55% and 8%; amoxicillin, 81% and 92%; ceftriaxone, 63% and 83%; meropenem, 96% and 100%; and 100% for both species with clindamycin, rifampin, levofloxacin, ofloxacin, quinupristin/dalfopristin, and vancomycin.

Anti-Bacterial Agents↗

PubMed2001

Spectrum and activity of three contemporary fluoroquinolones tested against Pseudomonas aeruginosa isolates from urinary tract infections in the SENTRY Antimicrobial Surveillance Program (Europe and the Americas; 2000): more alike than different!

The spectrum and potency of ciprofloxacin, gatifloxacin and levofloxacin was compared to that of 10 other agents against urinary tract isolates of Pseudomonas aeruginosa among patients in the year 2000 SENTRY Antimicrobial Surveillance Program (Europe, Latin America, North America). Dramatic differences were observed between isolates in geographic areas with the most fluoroquinolone-resistant strains detected in Latin America (54.5% resistance) compared to resistance rates of 40.8-43.7% and 28.3-29.2% for Europe and North America, respectively. Overall, no significant differences were observed between the spectrums of these fluoroquinolones (37.1-38.8% resistance) for therapy of P. aeruginosa urinary tract infections in hospitalized patients. Generally, in this world wide sample, aminoglycosides, carbapenems (imipenem, meropenem), cefepime, and piperacillin with or without tazobactam possessed a wider range of activity and spectrum versus current P. aeruginosa clinical isolates.

Aminoglycosides↗

PubMed2002

Ciprofloxacin as broad-spectrum empiric therapy--are fluoroquinolones still viable monotherapeutic agents compared with beta-lactams: data from the MYSTIC Program (US)?

Antimicrobial susceptibility data from United States medical centers participating in the Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) surveillance program were analyzed. These results indicate that ciprofloxacin resistance in commonly encountered nosocomial pathogens has reached a level where fluoroquinolones may no longer provide assured empiric monotherapy for serious infections nor provide a spectrum as a co-drug equivalent to aminoglycosides. Local susceptibility testing data must be assessed before fluoroquinolone empiric therapy can be used with confidence.

Anti-Bacterial Agents↗

PubMed2002

Ertapenem (MK-0826), a new carbapenem: comparative in vitro activity against clinically significant anaerobes.

Ertapenem, a new long acting beta-lactam with broad-spectrum antimicrobial coverage, was tested in vitro to compare its activity against 556 clinical isolates of anaerobes to other established agents using a broth microdilution method as recommended by the NCCLS. Against all anaerobes ertapenem inhibited 99.1% of isolates at 4 microg/mL, had a mode MIC of 0.12 microg/mL, and showed activity comparable to imipenem, meropenem, trovafloxacin, piperacillin-tazobactam, and metronidazole. Five of the B. fragilis group (4 B. fragilis, 1 B. vulgatus) isolates tested showed reduced susceptibility (>or=8 microg/mL; <1%) to ertapenem while all isolates of Prevotella, Porphyromonas, Fusobacterium, and Peptostreptococcus were susceptible. Only piperacillin-tazobactam had susceptible MIC's for all test isolates followed by metronidazole and the carbapenems exhibiting low resistance rates (<1%).

Anti-Bacterial Agents↗

PubMed2002

Four-year evaluation of frequency of occurrence and antimicrobial susceptibility patterns of bacteria from bloodstream infections in Latin American medical centers.

As part of the Latin American arm of the SENTRY Antimicrobial Surveillance Program, 7,207 bacterial isolates collected consecutively from bloodstream infections (BSI) during the period of January 1997 through December 2000 were analyzed. Ten Latin American laboratories located in six countries participated in the study during each year. Antimicrobial susceptibility testing was performed using the reference NCCLS broth microdilution method. The most frequently isolated species were (n/%): Staphylococcus aureus (1,532/21.3%), Escherichia coli (1,239/17.2%), coagulase-negative Staphylococcus (1,002/13.9%), Klebsiella pneumoniae (664/9.2%), and Pseudomonas aeruginosa (470/6.5%). The prevalence of S. aureus as a cause of BSI increased from 20.5% in 1997 to 23.3% in 2000 (p = 0.011), but oxacillin-resistance rates remained relatively stable during this period (around 30%). Enterococci (216 isolates) showed low rates of resistance to both vancomycin (2.4%) and ampicillin (7.9%) and 72.7% of 289 Streptococcus pneumoniae isolates evaluated were susceptible to penicillin (MIC </=0.06 microg/mL). Resistance rates among Gram-negative bacilli were much higher than those reported in other regions evaluated in the SENTRY Program. The main antimicrobial resistance problems among these pathogens were the high prevalences of ESBL-producing E. coli (6.7%) and K. pneumoniae (47.3%), and carbapenem-resistance among P. aeruginosa (around 12%) and Acinetobacter spp. (around 10%). P. aeruginosa resistance rates to meropenem, piperacillin/tazobactam, amikacin, and ciprofloxacin showed a significant increase during the 4-year period evaluated. Resistance rates varied according to the country for several pathogen-antimicrobial combinations. In summary, resistance to most antimicrobial agents for a number of species implicated in bacteremia, especially among Gram-negative rods, has reached worrisome levels and continues to increase.

Anti-Bacterial Agents↗

PubMed2002

Salmonella spp. isolates causing bloodstream infections in Latin America: report of antimicrobial activity from the SENTRY Antimicrobial Surveillance Program (1997-2000).

Recent years have seen a dramatic rise in the incidence and severity of cases of human salmonellosis. In addition, multidrug resistant strains have arisen. The objective of this study was to characterize the antimicrobial susceptibility profile of Salmonella spp. clinical isolates collected from Latin American medical centers as part of the SENTRY Antimicrobial Surveillance System. A total of 144 bloodstream Salmonella spp. isolates were collected between 1997 and 2000. The susceptibility to diverse antimicrobial agents was tested by broth microdilution techniques according to the NCCLS recommendations. The Salmonella spp. strains were more frequently collected from adult patients (67.0%; 21-60 years) and isolated from Chile (28.5%) > Brazil (25.0%) > Mexico (18.8%) > Colombia (11.8%). Ampicillin (MIC(50), 1 microg/ml) showed good in vitro activity (92.4% susceptibility). Meropenem (MIC(50), 0.06 microg/ml) and gatifloxacin (MIC(50), 0.03 microg/ml) were the most potent compounds against the Salmonella spp. isolates (100.0% susceptible) followed by piperacillin/tazobactam (99.3%), ceftazidime (98.6%), ceftriaxone (98.6%), and amoxicillin/clavulanic acid (94.4%). The lowest susceptibility rates were observed for tetracycline (87.5%) and trimethoprim/sulfamethoxazole (91.7%). Four of 144 (2.8%) Salmonella spp. isolates demonstrated an ESBL phenotype; however, only two (1.4%) were confirmed as an inhibitable ESBL producer. The results of this study show that multidrug resistance, especially fluoroquinolone resistance, does not represent a serious problem among Salmonella isolates collected from the Latin American medical centers as monitored by the SENTRY Program.

Adolescent↗