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PubMed2003

Analysis of three outbreaks due to Klebsiella species in a neonatal intensive care unit.

OBJECTIVE: To investigate the clinical, microbiological, and epidemiologic features of three outbreaks caused by Klesiella during 3 years. SETTING: Neonatal intensive care unit of a university hospital. PATIENTS: Thirty affected neonates. METHODS: Data were collected through chart reviews and conversations with physicians. Screening samples were obtained from the staff, the neonates, and the environment. Antibiogram typing and arbitrarily primed polymerase chain reaction-based fingerprinting were used to type the strains. RESULTS: The first outbreak had 13 K. pneumoniae strains isolated. The second outbreak had 10 K. oxytoca strains isolated. The third outbreak had 20 K. pneumoniae strains isolated. More than half of the patients had low birth weights, were premature, and underwent mechanical ventilation and intravenous catheterization. Approximately three-fourths of the patients died. The isolates tested were completely susceptible to meropenem, cefoxitin, and ciprofloxacin and were resistant to cephalothin. More than half of these strains were resistant to many beta-lactam antibiotics, amikacin, and trimethoprim/sulfamethoxazole. Typing procedures yielded 3 antibiotypes and 3 genotypes among the isolates of the first outbreak, 3 antibiotypes with 1 subtype and 2 genotypes with 1 subtype in the second outbreak, and 2 antibiotypes and 2 genotypes in the third outbreak. CONCLUSIONS: Klebsiella outbreaks mainly affected premature neonates with intravenous catheters, mechanical ventilation, or both. The high mortality rate (76.7%) was notable. Resistance to multiple antibiotics, but mainly to broad-spectrum beta-lactam antibiotics, was observed, particularly in K. pneumoniae isolates. Molecular typing indicated that the three outbreaks were not related to one other.

Anti-Bacterial Agents↗

PubMed2006

Emergence of carbapenem resistance in Acinetobacter baumannii recovered from blood cultures in Australia.

We describe the first emergence of carbapenem-resistant Acinetobacter baumannii in Australia. Ninety A. baumannii isolates recovered from cultures of blood specimens from 69 patients were analyzed. Overall, 58 isolates (64%) were resistant to meropenem. The chi 2 test for linear trend revealed that emergence of carbapenem resistance was statistically significant during the 32-month study period. Selected isolates were of the same clonal type, and no genes encoding carbapenemases were identified.

Acinetobacter baumannii↗

PubMed1999

Is monotherapy for febrile neutropenia still a viable alternative?

Monotherapy for empirical treatment of febrile neutropenia is effective and often less costly than combination therapy but remains controversial. The controversy results from observations that combination therapy for Pseudomonas aeruginosa improved outcomes, and this approach became a standard. Many subsequent publications, including the Infectious Diseases Society of America guidelines for febrile neutropenia, now support monotherapy. However, changes in the pathogens involved in febrile neutropenia and in their resistance prompt a reevaluation. In the evaluation of new antibiotics, recent trials comparing either cefepime or meropenem with combination therapy or with ceftazidime confirm that monotherapy remains a viable therapeutic approach, with infectious mortality in the 5% range in all arms. The choice of monotherapy should, however, be made on the basis of resistance patterns seen in an institution. The agent selected should be very active against the organisms that are likely to cause rapidly fatal infections, and clinicians must be prepared to modify monotherapy as appropriate.

Anti-Bacterial Agents↗

PubMed1999

Survey of bloodstream infections due to gram-negative bacilli: frequency of occurrence and antimicrobial susceptibility of isolates collected in the United States, Canada, and Latin America for the SENTRY Antimicrobial Surveillance Program, 1997.

During 1997, a total of 4,267 nosocomial and community-acquired bloodstream infections due to gram-negative organisms were reported from SENTRY hospitals in Canada (8 sites), the United States (30 sites), and Latin America (10 sites). Escherichia coli was the most common isolate (41% of all gram-negative isolates), followed by Klebsiella species (17.9%), Pseudomonas aeruginosa (10.6%), and Enterobacter species (9.4%). For all gram-negative isolates combined, the most active antimicrobials tested were meropenem, imipenem, and cefepime. The quinolones levofloxacin (MIC90, 2 microg/mL), ciprofloxacin (MIC90, 1 microg/mL), gatifloxacin (MIC90, 2 microg/mL), sparfloxacin (MIC90, 2 microg/mL), and trovafloxacin (MIC90, 2 microg/mL) were also active against most isolates. Bloodstream infection isolates from Latin America were uniformly more resistant to all classes of antimicrobial agents tested than were isolates from Canada or the United States. Resistance phenotypes consistent with extended-spectrum beta-lactamase production were also most common among E. coli and Klebsiella species from Latin America. Further investigation of the reasons for regional differences in resistance patterns is needed, as is ongoing surveillance to detect resistance trends and to guide antimicrobial use.

Bacteremia↗

PubMed2001

Antibiotic persistence: the role of spontaneous DNA repair response.

Persisters are a small proportion of a bacterial population that exists in a physiological state permitting survival despite the lethal activity of antibiotics. To explain this phenomenon, it has been suggested that persisters are bacteria repairing spontaneous errors of DNA synthesis. To verify this assumption, Escherichia coli AB1157 and its lexA3 derivative were exposed to a dose 6x MIC of various antibiotics representative of different molecular mechanisms of action (ampicillin, ceftriaxone, meropenem, amikacin, ciprofloxacin). Bacterial cell counts, after 24 hr of exposure to the antimicrobials, revealed a reduction of about 90% of viable organisms in the lexA3 strains in comparison to the lexA+. In several cases, the number of colony-forming units decreased below the limit of assay. This behavior was noted with all antibiotics used, alone or in combination (amikacin plus ceftriaxone and amikacin plus ciprofloxacin). The same experiments were repeated using E. coli AB1157 cultured in the presence of mitomycin C (0.25x MIC), and the number of survivors exceeded by about 90% the values found in the nonexposed control. In contrast, in the sulA background, mitomycin C reacted synergically with all the antibiotics tested causing a strong reduction of the survivors in comparison with the control. The addition of chloramphenicol (0.125x MIC), on the contrary, caused a reduction of the number of survivors of about 90%. These findings indicate that, when DNA repair is active (a mechanism known to block cell division), the number of survivors is greater than that observed with lexA3. Thus, in addition to other possible explanations, persisters might be a fraction of bacteria that during antibiotic treatment are not growing because they are repairing spontaneous errors of DNA synthesis.

Anti-Bacterial Agents↗

PubMed2002

Metallo-beta-lactamase VIM-2 in clinical isolates of Pseudomonas aeruginosa from Portugal.

Resistance to carbapenems is emerging, and it is a great problem to therapeutics. Three isolates of Pseudomonas aeruginosa from a Portuguese hospital identified in urine and sputum, in 1995, presented a high-level resistance to imipenem (> 32 mg/L). Afterward, one isolate of P. aeruginosa recovered from urine of an ambulatory patient in 1998 showed high resistance to imipenem and meropenem. The resistance to carbapenems in these strains was associated with the production of a class B beta-lactamase, as was demonstrated by imipenem hydrolysis and inhibition by EDTA. Using primers described for bla(IMP) and bla(VIM), the amplification of the latter was observed in all isolates and a VIM-2 metallo-enzyme was identified. The pulsed-field gel electrophoresis (PFGE) patterns of these isolates were indistinguishable, suggesting dissemination to the community of this VIM-2 producer.

Anti-Bacterial Agents↗

PubMed2003

Diversity of ampicillin-resistance genes in Haemophilus influenzae in Japan and the United States.

Clinical isolates of Haemophilus influenzae from Japan (n = 296) and the United States (n = 100) were tested by the microdilution method for susceptibility in vitro to 10 beta-lactam antibiotics and molecular mechanisms of beta-lactam resistance. For all isolates, PCR was used to identify six elements, including beta-lactamase-producing ampicillin (AMP)-resistance (BLPAR) and beta-lactamase-nonproducing AMP-resistance (BLNAR) genes as follows: (1) TEM-1 type beta-lactamase gene, (2) ROB-1 type beta-lactamase gene, (3) part of normal ftsI gene encoding PBP3, which is involved in septal peptidoglycan synthesis, (4) a portion of the ftsI gene possessing some amino acid substitutions commonly detected in BLNAR strains, (5) p6 gene encoding P6 membrane proteins specific to H. influenzae, and (6) serotype b capsule gene. In Japanese and U.S. isolates, respective prevalences of each resistance class in Japan and the United States were 55.1% and 46% for beta-lactamase-nonproducing, AMP-susceptible (BLNAS); 3.0% and 26% for the TEM-1 type beta-lactamase gene; 0% and 10% for the ROB-1 type; 26.4% and 13% for low-BLNAR with a low degree of AMP resistance; and 13.2% and 0% for BLNAR strains. A few remaining isolates were beta-lactamase-producing strains with a mutation in the ftsI gene. MICs of all beta-lactam agents against low-BLNAR strains were 2-8 times higher than against BLNAS. MICs of cephalosporin antibiotics against BLNAR strains were 16-32 times higher than against BLNAS. The rank order of beta-lactam MIC90 values against BLNAR strains was piperacillin = ceftriaxone = cefditoren (0.25 microg/ml), meropenem (0.5), cefotaxime (1), AMP = cefpodoxime (8), cefdinir (16), amoxicillin (16), and cefaclor (64). Serotype b isolates were few in both countries (2.4% in Japan, 3% in the United States). Differences in proportions of respective AMP-resistant genes in H. influenzae isolates between the two countries might reflect differences in antibiotic agents ordinarily given to outpatients with community-acquired bacterial infections.

Ampicillin Resistance↗

PubMed2000

The role of beta-lactam antimicrobials as single agents in treatment of intra-abdominal infection.

Broad-spectrum beta-lactam antibiotics have several advantages in the treatment of intra-abdominal infections. These agents are effective against gram-negative rods and anaerobes, reach therapeutic levels rapidly after parenteral administration, and, in the absence of penicillin allergy, generally exhibit low toxicity. The second-generation cephalosporins (e.g., cefoxitin, cefotetan) are used widely in surgical prophylaxis, trauma, and treatment of mild-to-moderate community-acquired infections, but limitations in their spectra and microbial resistance restrict their utility in more serious infections. Extended-spectrum penicillin/beta-lactamase-inhibitor combinations are effective in the treatment of intra-abdominal infections and include enterococci in their spectrum. Gram-negative aerobe resistance has developed to ampicillin/sulbactam. Piperacillin/tazobactam, a ureidopenicillin with increased gram-negative coverage and enhanced antipseudomonal activity, has proved to be effective in clinical trial therapy for intra-abdominal infections. The very broad spectrum carbapenems--imipenem/cilastatin and meropenem--are effective for serious infections or resistant organisms and are often used in the intensive care unit or for nosocomial intra-abdominal infection. These classes of beta-lactams comprise a range of antimicrobials that can be targeted effectively as single agents to both prevention and treatment of intra-abdominal infection.

Abdomen↗

PubMed2006

Amoebic hepatic abscesses in an HIV-positive patient.

Herein we report the case of hepatic amoebic abscesses in an HIV-positive Italian seaman with a history of promiscuous heterosexual intercourse. In October 2004, the patient was hospitalized because of fever and recurring abdominal pain. Abdominal ultrasonography revealed six hepatic hypoechoid oval lesions with hyperechoid margins. Stool samples were negative for parasites and bacteria, and serology for Entamoeba histolytica was also negative. Therapy with meropenem plus levofloxacin was initiated. After a partial resolution of clinical symptoms and reduction of three hepatic lesions, the patient was again hospitalized in December 2004, because of recurring intense pain at the right hypochondrium and fever. At this time, one hepatic lesion at the sixth segment was enlarged, two lesions were unchanged, and the remaining three smaller abscesses were resolved. Serum antibodies for E. histolytica and amoebic antigens on the largest abscess drainage were positive; moreover, E. histolytica was also identified on drainage fluid with polymerase chain reaction (PCR). Therapy with metronidazole followed by paromomycin improved both symptoms and radiographic images. This case report suggests that in HIV-infected patients, invasive amoebiasis should be considered and atypical aspects, such as multiple hepatic lesions, delayed positivity of serology for E. histolytica, and possible bacterial superinfection should be evaluated.

Amebicides↗

PubMed1998

Streptococcus mitis with unusually high level resistance to beta-lactam antibiotics.

Penicillin-resistant oral streptococci constitute the genetic reservoir for beta-lactam resistance in S. pneumoniae. Here we report the isolation of clinical strains of S. mitis with unusually high MIC values for beta-lactam antibiotics; resistance to benzylpenicillin was 64 microg/ml and to cefotaxime 128 microg/ml. Among the beta-lactam compounds tested, only the carbapenems imipenem and meropenem showed MICs below 32 microg/ml. Both S. mitis strains were resistant to tetracycline and were highly resistant to aminoglycosides. Pulse field mapping of chromosomal DNA revealed identical patterns in both strains, indicating clonal identity of the two isolates. Using chromosomal S. mitis DNA, the laboratory strain S. pneumoniae R6 could be transformed in four successive steps to cefotaxime and benzylpenicillin resistance of 64 microg/ml. The results exemplify the importance of commensal streptococci for the development of cefotaxime resistance in S. pneumoniae.

Anti-Bacterial Agents↗

PubMed2006

Occurrence and characterization of carbapenemase-producing Enterobacteriaceae: report from the SENTRY Antimicrobial Surveillance Program (2000-2004).

Emergence and dissemination of Enterobacteriaceae isolates harboring carbapenemases in various geographic regions represents a significant threat to the management of nosocomial infections. Enterobacteriaceae isolates from the SENTRY Antimicrobial Surveillance Program (2000-2004) demonstrating decreased susceptibility to imipenem and meropenem (minimum inhibitory concentration [MIC], > or =2 mg/L) were evaluated for the production of metallo-beta-lactamases and serine carbapenemases using disk approximation and polymerase chain reaction (PCR) tests. Carbapenemase-producing strains were epidemiologically typed by automated riboprinting and pulsed-field gel electrophoresis (PFGE) to establish clonality. Among 37,557 Enterobacteriaceae (5 genus groups) evaluated, 119 (0.32%) had increased carbapenem MIC values, and a carbapenemase was identified in 51 (42.9%) of these strains. KPC-2 and KPC-3 were the most frequently occurring carbapenemases (24 isolates, 20.2%) in the United States and were detected in Klebsiella spp, Citrobacter spp., Enterobacter spp., and Serratia marcescens strains isolated in New York, Arkansas, and Virginia. SME-2-producing S. marcescens were isolated in the New York City area, Texas, and Ohio, while NMC-A was found in one E. cloacae strain from New York. In contrast, metallo-beta-lactamases were prevalent in Europe. IMP-1-producing E. cloacae (11 isolates) were detected in Turkey, while VIM-1-producing strains were found in Italy (Enterobacter spp.) and Greece (Klebsiella pneumoniae). Clonal dissemination of carbapenemase-producing strains was observed in several medical centers on both continents. The occurrence of carbapenemases in various Enterobacteriaceae remains rare but appears to be spreading geographically (not in Latin America), mainly with metallo-beta-lactamases being found in Mediterranean Europe and KPC enzymes in the New York City area.

Anti-Bacterial Agents↗

PubMed2006

A case of ventricular drainage infection with a rare pathogen in cerebrospinal fluid: vancomycin-resistant Enterococcus faecium.

The purpose of this study was to describe a patient, 7-month-old child with ventriculoperitoneal shunts for hydrocephalus with ventriculitis caused by vancomycin-resistant Enterococcus faecium. Two ventriculoperitoneal shunts were inserted just after birth and on the second month. On the sixth month, both shunts were removed because of dysfunction, and external drainage was inserted. The child developed fever, and lumbar puncture revealed a high leukocyte count and protein concentration after external drainage. Cerebrospinal fluid (CSF) cultures yielded E. faecium, which was resistant to ampicillin, erythromycin, gentamicin, penicillin G, vancomycin, and teicoplanin and was susceptible to chloramphenicol, ciprofloxacin, streptomycin, levofloxacin, and rifampin, as determined by the disk diffusion method. As a result of the antimicrobial susceptibility tests, multidrug antibiotic therapy was changed from vancomycin and ceftazidime to chloramphenicol, rifampin, and meropenem. In addition, a rifampin-clindamycin-impregnated shunt (The Codman Hakim Bactiseal, Raynham, MA) was inserted. The patient became afebrile, and CSF cultures were sterile after 15 days of yielding E. faecium. Implantation of the rifampin-clindamycin-impregnated shunt and timely use of appropriate antibiotics for 10 days according to antimicrobial susceptibility testing seem to be important in the resolution of vancomycin-resistant enterococci infections, especially in countries where linezolid and quinupristin-dalfopristin are not in use yet.

Cerebrospinal Fluid↗

PubMed1997

The challenge of penicillin-resistant Streptococcus pneumoniae meningitis: current antibiotic therapy in the 1990s.

Bacterial meningitis caused by Streptococcus pneumoniae is an important cause of neurological morbidity and mortality in both children and adults. With increasing antibiotic resistance in pneumococci and documented microbiological failure in treatment of pneumococcal meningitis with cefotaxime and ceftriaxone, the need for alternative antibiotic therapy is critical. Of the currently available options, vancomycin has shown the most promise, particularly when used in combination with ceftriaxone or cefotaxime. Rifampin, also used in combination with either ceftriaxone or cefotaxime, has demonstrated encouraging preliminary results against antibiotic-resistant pneumococci as well. Chloramphenicol has unexpectedly yielded discouraging clinical results in children with infection caused by penicillin-resistant strains. Of the investigational antibiotics currently in clinical trials for the treatment of meningitis, meropenem, a carbapenem-class antibiotic, has demonstrated increased activity against penicillin-resistant pneumococci compared with that of other beta-lactam antibiotics, while having a safety profile similar to that of the cephalosporins.

Adult↗

PubMed1990

The antibiotic sensitivity of bacteria isolated from the blood of patients in St Thomas' Hospital, 1969-1988.

We have monitored the antibiotic sensitivity of bloodstream isolates of common bacteria over a period of 20 years. Among the Gram-positive bacteria, the proportion of isolates of Staphylococcus aureus resistant to methicillin, erythromycin, fusidate, or gentamicin has increased marginally, while that of coagulase-negative staphylococci (mostly Staph. epidermidis) has increased markedly. Enterococci are becoming serially more resistant to high concentrations of aminoglycosides. The Enterobacteriaceae have become considerably less sensitive to ampicillin (and amoxycillin) and trimethoprim but more sensitive to the aminoglycosides, whilst their susceptibility to cefotaxime, ceftazidime, cefepime, cefpirome, imipenem, meropenem and temocillin has remained constant. We have some evidence that in-vitro resistance is clinically relevant since the mortality rate rises if inappropriate antibiotics are used empirically. Although many drug regimens could be used, we are able to recommend initial therapy with a combination of gentamicin and cefuroxime for most of our patients, the exceptions being those known to be infected with resistant organisms before the onset of septicaemia.

Coagulase↗

PubMed1991

Effect of media composition on the susceptibility of Xanthomonas maltophilia to beta-lactam antibiotics.

The susceptibility of Xanthomonas maltophilia strains to beta-lactams was shown to depend on the concentrations at which individual media were prepared. MIC and disc susceptibility tests were performed on solidified Mueller-Hinton and Iso-Sensitest media prepared at 0.1, 0.3, 1, and 3 x the concentrations recommended by the manufacturers. Nine of ten X. maltophilia strains tested showed increasing sensitivity to meropenem, cefotaxime, cefoperazone, piperacillin and latamoxef as the nutrient concentrations of the two media were increased. The opposite pattern was found with one strain (NCTC 10257) on Mueller-Hinton agar. This strain behaved inconsistently on Iso-Sensitest agar. Previous studies have shown that medium-dependent susceptibility in X. maltophilia is not related to beta-lactamase expression. The present study demonstrated that 22 and 25 kDa outer membrane proteins were induced on media with higher nutrient concentrations. The possible relationship of these proteins to sensitivity is considered.

Anti-Bacterial Agents↗

PubMed1992

In-vitro antimicrobial susceptibility of Rhodococcus equi.

Rhodococcus equi is an intracellular facultative, Gram-positive cocco-bacillary organism of increasing importance as a pulmonary pathogen in HIV-positive patients. This study was carried out to evaluate the optimal antibiotic combinations for treating such infections. Four human R. equi isolates and one reference strain were tested for their susceptibilities to 36 antibiotics. In-vitro the most active antibiotics were amikacin, gentamicin, netilmicin, erythromycin, clarithromycin, roxithromycin, ciprofloxacin, sparfloxacin, rifampicin, vancomycin, teicoplanin, doxycycline, minocycline, imipenem, meropenem and trimethoprim/sulphamethoxazole. The only bactericidal antibiotics were the aminoglycosides, ciprofloxacin, sparfloxacin and vancomycin. As determined by FIC indices, four combinations were synergistic: rifampicin-erythromycin, rifampicin-minocycline, erythromycin-minocycline and imipenem-amikacin. However, no antibiotic combinations were synergistic with the time-kill kinetic method at achievable serum concentrations or at ten-fold and half-fold the MICs. Frequencies of selection of antibiotic-resistant mutants determined at concentrations of five- and ten-fold the MICs ranged from less than 1 x 10(-8) for erythromycin and trimethoprim/sulphamethoxazole to 5 x 10(-4) for amikacin. These results may be of help in selecting the antibiotics for treating infected HIV-positive patients.

Anti-Bacterial Agents↗

PubMed1992

Decreased susceptibility of penicillin-resistant pneumococci to twenty-four beta-lactam antibiotics.

The in-vitro activity of 24 beta-lactam antibiotics was compared using three groups of pneumococci and an agar dilution method comprising 100 penicillin-susceptible, 100 intermediately penicillin-resistant, and 100 highly penicillin-resistant pneumococcal strains. Our results show that intermediately penicillin-resistant and highly penicillin-resistant pneumococci had decreased sensitivity to other beta-lactam agents. According to their relative in-vitro activity, the antimicrobials were classified into three groups. The first group included drugs more active than penicillin (imipenem, meropenem, cefotaxime, ceftriaxone, and cefpirome), which could be useful for the treatment of infections due to penicillin-resistant strains. The second group showed slightly lesser activity than did penicillin, and included: ampicillin, cefdinir, cefuroxime, cefoperazone, azlocillin, mezlocillin, piperacillin, cephalothin, and cefamandole. The remaining antibiotics (oxacillin, cefixime, ceftizoxime, cefetamet, cefaclor, ceftazidime, cefoxitin, cefonicid, and latamoxef) showed poor activity against penicillin-resistant strains, precluding their use for empirical treatment in areas with a high prevalence of penicillin-resistant strains.

Anti-Bacterial Agents↗

PubMed1995

Aeromonas infections and their treatment.

With advances in the identification and molecular taxonomy of Aeromonas spp., these organisms, which are widely distributed in the environment, are increasingly being recognised as human pathogens. Clinical infections include gastroenteritis, skin and soft tissue infections and bacteraemia. Antibiotic resistance poses a potential problem in the antimicrobial therapy of infections cased by Aeromonas spp. While most strains are susceptible to chloramphenicol, ciprofloxacin, co-trimoxazole and the aminoglycosides, the activity of amoxycillin/clavulanate and the acylureidopenicillins is inconsistent. Addition of a beta-lactamase inhibitor does not significantly enhance the activity of the acylureidopenicillins. Aztreonam and the carbapenems, imipenem and meropenem remain highly active. Although resistance to the first and second generation cephalosporins is variable, more than 90% of Aeromonas spp. are susceptible to the third generation agents. Of potential significance is the identification of chromosomally-encoded inducible beta-lactamases, associated with resistance to extended spectrum penicillins, cephalosporins, monobactams and carbapenems, in clinical isolates of Aeromonas spp. Two distinct enzymes are produced: the A1 enzyme, a serine beta-lactamase behaving as a group 1 cephalosporinase, and the A2 enzyme, a metallo beta-lactamase which hydrolyses a wide range of beta-lactam agents including the carbapenems. The clinical relevance of these enzymes in Aeromonas spp. is unclear.

Aeromonas↗