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PubMed1999

In-vitro effects of a combination of antipseudomonal antibiotics against multi-drug resistant Pseudomonas aeruginosa.

We evaluated the in-vitro effects of various combinations of five types of widely used antipseudomonal antibiotics (piperacillin, meropenem, ceftazidime, aztreonam and amikacin) against six Pseudomonas aeruginosa strains that were resistant to each of these antibiotics. Among two-drug combinations, the combinations of two beta-lactam antibiotics inhibited growth of one to three P. aeruginosa strains, while those of one beta-lactam antibiotic and amikacin inhibited growth of two to four strains. Among three-drug combinations, the combinations of three beta-lactam antibiotics inhibited growth of four to five strains, and those of two beta-lactam antibiotics and amikacin inhibited growth of five strains. These results suggest the potential usefulness of a combination of two beta-lactam antibiotics and amikacin or that of three beta-lactam antibiotics in treating multi-drug resistant P. aeruginosa infections.

Amikacin↗

PubMed2000

Antimicrobial resistance amongst Klebsiella spp. collected from intensive care units in Southern and Western Europe in 1997-1998.

A 1994 survey of 35 intensive care units (ICUs) in Western and Southern Europe found extended-spectrum beta-lactamases (ESBLs) in 220/966 (23%) klebsiellae. A follow-up survey from May 1997 to October 1998 collected klebsiellae from 24 ICUs, including 23 that participated in 1994. Twenty-one ICUs sent 433 eligible isolates, of which 110 (25%) had ESBLs. The prevalence of ESBLs had not changed significantly from 1994 but the proportion of ESBL-producers resistant to piperacillin/tazobactam had risen from 31% to 63% (P < 0.001), and most of this resistance was high level (MICs >/= 128 + 4 mg/L). The proportion of Klebsiella oxytoca isolates hyperproducing K1 beta-lactamase rose from 8% in 1994 to 21% in 1997-1998 (P < 0. 001). Most klebsiellae (99%) were very susceptible to meropenem (mode MIC 0.03 mg/L) but three had decreased susceptibility (MICs 2-4 mg/L). These could not hydrolyse carbapenems. Aminoglycoside resistance was not significantly changed in prevalence from 1994; ciprofloxacin resistance occurred in 31% of ESBL-producers in both years, but had increased among non-producers (2% in 1994 versus 7% in 1997-1998, P < 0.001).

Anti-Bacterial Agents↗

PubMed2005

Peritumoral Citrobacter koseri abscess associated with parasagittal meningioma.

OBJECTIVE AND IMPORTANCE: This is the second report of a Citrobacter-associated brain abscess in an adult and the first report of its association with an intradural tumor. Excluding those associated with trauma, neurosurgical procedures, and proximity to the skull base, only seven other cases of abscesses associated with intracranial tumors have been published. Five of seven tumor-associated abscesses with a microbiological diagnosis involved gram-negative bacteria, a finding that may indicate a predilection of these microorganisms for intracranial tumors. CLINICAL PRESENTATION: A 78-year-old female patient presented with a 6-month history of confusion and personality changes. Her medical history included paroxysmal atrial fibrillation and a 10-day course of high-dose dexamethasone but no other predisposing conditions for sepsis. She was afebrile, had no focal neurological deficits, and had no systemic abnormalities on examination. Computed tomographic imaging revealed a noncalcified, homogeneously enhancing, 3-cm-diameter, extra-axial tumor associated with the right anterior falx cerebri. The tumor did not extend to the skull base. INTERVENTION: At craniotomy, 10 to 20 ml of thick pus was found around the posteroinferior surface of the tumor. On extended culture, this material demonstrated Citrobacter koseri growth, which was effectively treated with ceftriaxone followed by meropenem and one repeated abscess aspiration. No systemic source of the infection was found. CONCLUSION: The characteristic endothelial invasiveness of Citrobacter and related gram-negative bacteria may predispose to the formation of abscesses in association with intracranial tumors.

Aged↗

PubMed2002

Recurrent fatal drug-induced toxic epidermal necrolysis (Lyell's syndrome) after putative beta-lactam cross-reactivity: Case report and scrutiny of antibiotic imputability.

OBJECTIVE: A series of antibiotics may be responsible for toxic epidermal necrolysis. We report two successive episodes of toxic epidermal necrolysis in the same patient. Drug imputability criteria designate a cross-reactivity between two antibiotics of different chemical classes but sharing the beta-lactam ring in common. DESIGN: Descriptive case report and review of the literature. SETTING: Medical intensive care unit in a university medical center. PATIENT AND MAIN RESULTS: A 75-yr-old woman developed a first episode of toxic epidermal necrolysis (involving 40% of the body surface) after intake of cefotaxime, a third-generation cephalosporin. Perfusions of high-dose immunoglobulins rapidly improved the lesions, followed by partial reepithelialization in 5 days. Sepsis required the administration of meropenem, which is a carbapenem antibiotic. The epidermal destruction immediately recurred, with extension to previously uninvolved skin areas and fatal consequences. CONCLUSIONS: The beta-lactam ring present in cephalosporins and carbapenems represents the putative chemical structure responsible for the presently reported cross-reactivity to two antibiotics of different classes. Drugs having any chemical similarity to the initial culprit compound should be strictly avoided when possible in the management of toxic epidermal necrolysis.

Aged↗

PubMed2003

Carbapenems in pediatrics.

Antimicrobial resistance is increasing among bacterial pathogens. In particular, organisms producing extended spectrum beta-lactamase enzymes (ESBLs) and AmpC chromosomal beta-lactamase enzymes are resistant to third generation cephalosporins and pose a formidable challenge in the management of seriously ill patients. Carbapenems are a class of broad-spectrum antibiotics with stability against ESBL and AmpC chromosomal beta-lactamases. They are well tolerated by patients. This review will examine the pharmacokinetic and pharmacodynamic properties of two carbapenems imipenem and meropenem and discuss their clinical use in children. References are limited to the English language and extend back to 1980. Sources include computerized databases such as MEDLINE searched using PubMed, and bibliographies of recent articles and books. Approximately 50% of the articles initially reviewed are included in the bibliography. Carbapenems are efficacious in the treatment of a variety of bacterial infections including meningitis, pneumonia, intraabdominal infections, bone, joint and urinary tract infections. The broad spectrum activity and comparatively low toxicity of carbapenems make them valuable therapeutic agents in the treatment of seriously ill patients with bacterial infections. These agents should be used judiciously in order to minimize the risk for development of carbapenem-resistant pathogens.

Child↗

PubMed2005

Multiple spleen and liver abscesses due to Yersinia enterocolitica septicemia in a child with congenital sideroblastic anemia.

In patients with iron overload, opportunistic infections are an underestimated risk. Yersinia enterocolitica is a rare organism to be isolated in this setting. The authors report a case of disseminated Y. enterocolitica sepsis in a 5-year-old boy with sideroblastic anemia. Ultrasound examination revealed massive ascites, a pseudo-appendicitis, and hypoechogenic lesions corresponding to abscess formations in the liver and spleen. The initial antibiotic therapy consisted of cefotaxime, gentamicin, and metronidazole, but only treatment with ciprofloxacin and meropenem led to defervescence and clinical stabilization. The risk of developing uncommon infections in patients with iron overload should be acknowledged by all physicians, and the relevance of ultrasound examination is emphasized. In this case, only a detailed history revealed that several days before the onset of diarrhea, the child was feeding a deer; this is how infection was probably acquired.

Anemia, Sideroblastic↗

PubMed2006

Evidence-based treatment of acute pancreatitis: a look at established paradigms.

BACKGROUND: The management of acute pancreatitis (AP) is still based on speculative and unproven paradigms in many centers. Therefore, we performed an evidence-based analysis to assess the best available treatment. METHODS: A comprehensive Medline and Cochrane Library search was performed evaluating the indication and timing of interventional and surgical approaches, and the value of aprotinin, lexipafant, gabexate mesylate, and octreotide treatment. Each study was ranked according to the evidence-based methodology of Sackett; whenever feasible, we performed new meta-analyses using the random-effects model. Recommendations were based on the available level of evidence (A=large randomized; B=small randomized; C=prospective trial). RESULTS: None of the evaluated medical treatments is recommended (level A). Patients with AP should receive early enteral nutrition (level B). While mild biliary AP is best treated by primary cholecystectomy (level B), patients with severe biliary AP require emergency endoscopic papillotomy followed by interval cholecystectomy (level A). Patients with necrotizing AP should receive imipenem or meropenem prophylaxis to decrease the risk of infected necrosis and mortality (level A). Sterile necrosis per se is not an indication for surgery (level C), and not all patients with infected necrosis require immediate surgery (level B). In general, early necrosectomy should be avoided (level B), and single necrosectomy with postoperative lavage should be preferred over "open-packing" because of fewer complications with comparable mortality rates (level C). CONCLUSIONS: While providing new insights into key aspects of AP management, this evidence-based analysis highlights the need for further clinical trials, particularly regarding the indications for antibiotic prophylaxis and surgery.

Acute Disease↗

PubMed2000

Prevalence of the carbapenemase gene (cfiA) among clinical and normal flora isolates of Bacteroides species in Hungary.

The carbapenemase gene (cfiA) was detected in 4 (5.7%) of 70 clinical isolates of Bacteroides fragilis from different parts of Hungary. Among 24 other Bacteroides species isolated from infectious processes or from normal faecal flora, none was cfiA-positive. The MIC of imipenem and meropenem for all cfiA-positive B. fragilis isolates was < or =0.25 mg/L, but 17% of the B. fragilis and 46% of the non-fragilis Bacteroides isolates exhibited reduced susceptibility to imipenem (MICs 0.5-2 mg/L). Only one of these isolates produced increased levels of beta-lactamase. No difference was observed in the outer-membrane proteins of B. fragilis isolates that harboured the cfiA gene and those with reduced susceptibility to imipenem.

Bacterial Proteins↗

PubMed2004

Effect of carbapenems on the transcriptional expression of the oprD, oprM and oprN genes in Pseudomonas aeruginosa.

The effects of imipenem and meropenem on the transcriptional expression of resistance-related genes oprD, oprM and oprN in Pseudomonas aeruginosa were studied by quantitative real-time PCR. Four strains were examined: the type strain PT5 (PAO1), its derivatives M7 and PT149, and a clinical isolate, PaKT3. The derivative M7 is a nalB mutant, overexpressing the MexAB-OprM pump, and the derivative PT149 is a nfxC-type mutant, overexpressing the MexEF-OprN pump while it is down-regulated for the OprD protein. After 18 h incubation in broth, the cultures were divided into three portions. Two were supplemented with antibiotics and the other was left antibiotic-free as the control. After a further 45 min incubation, total RNA was isolated from the strains by guanidine denaturation and acid-phenol/chloroform extraction. DNA-free total RNAs were immediately reverse-transcribed by MMuLV reverse transcriptase. Concentrations of mRNAs obtained by quantitative PCR were expressed relative to uninduced portions of the strains. The results showed that oprD was relatively stable against carbapenem antibiotics. oprM was induced significantly by imipenem in only one strain and oprN was induced by imipenem in most of the strains. The responses at the mRNA level found here were unexpected and suggested a chaotic, unpredictable regulatory mechanism.

Anti-Bacterial Agents↗

PubMed2005

Empirical antimicrobial monotherapy in patients after high-dose chemotherapy and autologous stem cell transplantation: a randomised, multicentre trial.

We report on 232 patients undergoing autologous haematopoietic stem cell transplantation (ASCT) entered into a multicentre, randomised trial comparing the efficacy and tolerability of meropenem (MPM) with that of piperacillin/tazobactam (P/T) as empirical antimicrobial first-line therapy for febrile neutropenia. In 27.6% of patients in the MPM group and 22.4% in the P/T group, therapy was initially supplemented with a glycopeptide for venous catheter infection or bacteraemia because of coagulase-negative staphylococci. Complete response rate after 72 h was 63.8% in the MPM group and 49.6% in the P/T group (P = 0.034). Overall complete response rate after treatment modification was 94.0% in the MPM group and 93.1% in the P/T group. Median time to defervescence was 2 d in the MPM group and 3 d in the P/T group. The most frequently isolated pathogens were Gram-positive cocci. Treatment was well tolerated in both groups. One patient (0.4%) died from infection. Empirical first-line therapy with MPM as well as with P/T is safe and effective in febrile episodes emerging after ASCT. Higher response rates to primary treatment can be achieved with MPM.

Adolescent↗

PubMed2004

Results of two worldwide surveys into physician awareness and perceptions of extended-spectrum beta-lactamases.

An omnibus survey of microbiologists (n = 400) and a survey of participants (n = 49) in the Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) programme were conducted to determine the awareness and prevalence of extended-spectrum beta-lactamases (ESBLs), and the regularity and method of screening. Of the omnibus survey participants, 69% screened regularly for ESBLs, compared with 83% of MYSTIC participants. In both surveys, ESBLs were more common in Klebsiella pneumoniae (73% and 79%, respectively) and Escherichia coli (63% and 81%, respectively) than in other bacteria. The surveys demonstrated that awareness of, and testing for, ESBLs is inconsistent.

Anti-Bacterial Agents↗

PubMed2006

Pathophysiology of in-vitro induced filaments, spheroplasts and rod-shaped bacteria in neutropenic mice.

This study compared the in-vitro properties and in-vivo effects of Escherichia coli filaments, spheroplasts and normal cells in a murine thigh infection model. E. coli was exposed to ceftazidime, meropenem or saline to obtain filaments, spheroplasts or normal bacilli, which were then injected into neutropenic mice. After 24 h, morphology, CFUs, local and circulating endotoxin levels, cytokine levels and mortality were recorded, and correlations between bacterial and host parameters of infection were investigated. Filaments and spheroplasts contained more endotoxin/CFU than controls. Histological studies showed that morphologically altered bacteria changed into rod-shaped cells in the absence of antibiotics. Bacterial spread to the liver was significantly higher in mice challenged with rod-shaped cells, compared with antibiotic-exposed bacteria (p 0.007). Muscle endotoxin levels correlated significantly with circulating interleukin (IL)-6 and tumour necrosis factor (TNF)-alpha, and both pro-inflammatory cytokines were correlated significantly (p 0.011). Despite a tendency toward higher local and systemic concentrations of endotoxin in the filament group, inflammatory responses and survival did not differ between groups. It was concluded that morphologically altered bacteria contain more endotoxin and can regain a rod shape after withdrawal of antibiotics, while non-antibiotic-exposed bacteria show greater spread to the liver. There was a clear intra-individual relationship between local endotoxin, systemic endotoxin, TNF-alpha and IL-6 production, but these parameters did not differ among groups.

Animals↗

PubMed1993

[Influence of urine pH and cations on antimicrobial activities of penems].

We compared the antimicrobial activities of penems in human urine with those in Mueller-Hinton broth in order to clarify the usefulness of penems for urinary tract infections. Furthermore, we also investigated the influence of urine components, such as pH, magnesium concentration and calcium concentration, on the antimicrobial activities of penems. Three penems, i.e., imipenem, panipenem and meropenem were employed. And two bacterial strains, i.e., Escherichia coli NIHJ JC-2 and Pseudomonas aeruginosa 18s, were tested. There was no significant difference in MBCs between human urine and Mueller-Hinton broth against E. coli. However, MBCs of penems in human urine was lower than those in Mueller-Hinton broth against P. aeruginosa. On the other hand, MBCs of penems against these two strains were low when urine pH was high or urine calcium concentration was low. No influence of urine magnesium concentration on MBCs of penems was seen. From these results, it was suggested that we should measure the antimicrobial activities of penems not only in Mueller-Hinton broth, but also in human urine, when we administer penems to patients with urinary tract infections. And we should foresee the clinical effects of penems against urinary tract infections paying attention to urine pH of the patients.

Cations, Divalent↗

PubMed2004

[Antimicrobial susceptibilities of Streptococcus pneumoniae and Haemophilus influenzae isolated from children with meningitis].

Between April 2001 and March 2003, we studied minimum inhibitory concentrations (MIC) and minimum bactericidal concentrations (MBC) of 7 strains of Streptococcus pneumoniae and 8 strains of Haemophilus influenzae isolated from children with meningitis. The age range of the patients was from 4 months to 5 years. Susceptibilities of ampicillin (ABPC), cefotaxime (CTX), panipenem (PAPM), and vancomycin (VCM) in S. pneumoniae and those of ABPC, CTX, ceftriaxone (CTRX), and meropenem (MEPM) in H. influenzae were measured. MICs of ABPC, CTX, PAPM, and VCM to S. pneumoniae were < or = 0.06-2, < or = 0.06-0.5, < or = 0.06, and 0.25-0.5 microgram/ml and MICs of ABPC, CTX, CTRX, and MEPM to H. influenzae were 0.12-64, < or = 0.06-0.5, < or = 0.06-0.12, and < or = 0.06-0.25 microgram/ml, respectively. In 5 of all strains, difference between MIC and MBC to ABPC was observed. Four strains out of them had mutations of penicillin binding protein genes measured by PCR methods.

Ampicillin↗

PubMed1994

In vitro activity of biapenem (L-627), a new carbapenem, against anaerobes.

We tested 441 clinical strains of anaerobes by using a broth microdilution method to determine the in vitro activity of biapenem for comparison with those of other agents. Biapenem had activity comparable to those of imipenem and meropenem against all groups of anaerobes with MICs for 90% of the strains tested of 0.06 to 2 micrograms/ml. Against the Bacteroides fragilis group, biapenem was more active than ampicillin-sulbactam, ticarcillin-clavulanate, piperacillin, cefoxitin, cefotaxime, and ceftriaxone. Biapenem was also active against all of the B. capillosus, Prevotella, Clostridium, and Eubacterium strains and anaerobic cocci tested. Against all of the anaerobes tested, biapenem was 32- and 4-fold more active than clindamycin and metronidazole, respectively. These data indicate broad-spectrum activity by biapenem against anaerobes.

Bacteria, Anaerobic↗

PubMed1997

Effect of pH on in vitro antimicrobial susceptibility of the Bacteroides fragilis group.

We studied the effect of pH (7.1, 6.3, and 5.8) on the in vitro susceptibilities of 59 isolates of Bacteroides fragilis and 60 isolates of other B. fragilis group species to trovafloxacin, ciprofloxacin, clindamycin, ampicillin-sulbactam, piperacillin-tazobactam, imipenem, and meropenem. For each agent tested the geometric mean MIC was highest at pH 5.8, intermediate at pH 6.3, and lowest at pH 7.1. The magnitude of the pH effect varied greatly among different antibiotics. These data show that an acidic pH decreases the in vitro susceptibilities of the B. fragilis group to several antibiotics.

Ampicillin↗

PubMed2000

In vitro activities of membrane-active peptides alone and in combination with clinically used antimicrobial agents against Stenotrophomonas maltophilia.

The in vitro activities of buforin II, cecropin P1, and magainin II, alone and in combination with six clinically used antimicrobial agents, against 12 clinical isolates of Stenotrophomonas maltophilia were investigated. Antimicrobial activities were measured by MIC and time-kill studies. The isolates were susceptible to the peptides at concentrations in the range of 0.50 to 16 microg/ml. Synergy was observed when the peptides were combined with polymyxin E, meropenem, ceftazidime, piperacillin, and clarithromycin.

Anti-Bacterial Agents↗

PubMed2002

Carbapenem-resistant Pseudomonas aeruginosa in malaysia producing IMP-7 beta-lactamase.

We have isolated and identified a carbapenem-resistant Pseudomonas aeruginosa strain from Malaysia that produces an IMP-7 metallo-beta-lactamase. This isolate showed high-level resistance to meropenem and imipenem, the MICs of which were 256 and 128 micro g/ml, respectively. Isoelectric focusing analyses revealed pI values of >9.0, 8.2, and 7.8, which indicated the possible presence of IMP and OXA. DNA sequencing confirmed the identity of the IMP-7 determinant.

Anti-Bacterial Agents↗