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Empirical antibiotic monotherapy for febrile neutropenia: systematic review and meta-analysis of randomized controlled trials.

OBJECTIVES: Early, empirical broad-spectrum antibiotic treatment is the established practice for febrile neutropenia. Several beta-lactams are accepted for monotherapy. We asked whether patients' outcomes are influenced by the chosen beta-lactam. METHODS: Systematic review and meta-analysis of randomized controlled trials comparing anti-pseudomonal beta-lactams administered as empirical monotherapy for febrile neutropenia, with or without vancomycin. The search included The Cochrane Library, PubMed, Embase, Lilacs databases, bibliography, conference proceedings, trial registries and FDA new drug approvals. Two reviewers independently applied selection criteria, performed quality assessment and extracted the data. Trials assessing the same beta-lactam were pooled using the fixed effect model. Relative risks (RRs) with 95% confidence intervals (CIs) were calculated. The primary outcome assessed was all-cause mortality. RESULTS: Thirty-three trials fulfilled inclusion criteria. Cefepime was associated with higher all-cause mortality at 30 days than other beta-lactams (RR 1.44, 95% CI 1.06-1.94, 3123 participants). Carbapenems were associated with fewer treatment modifications, including addition of glycopeptides, than ceftazidime or other comparators. Adverse events were significantly more frequent with carbapenems, specifically pseudomembranous colitis (RR 1.94, 95% CI 1.24-3.04, 2025 participants). All-cause mortality was unaltered. Piperacillin/tazobactam was compared only with cefepime and carbapenems, in six trials. No significant differences were demonstrated with paucity of data for all-cause mortality. CONCLUSIONS: The use of cefepime for febrile neutropenia is associated with increased mortality and should be carefully considered pending further analysis. Empirical use of carbapenems entails fewer treatment modifications, but an increased rate of pseudomembranous colitis. Ceftazidime, piperacillin/tazobactam, imipenem/cilastatin and meropenem appear to be suitable agents for monotherapy.

Anti-Bacterial Agents↗

Outbreak of multiple clones of imipenem-resistant Acinetobacter baumannii isolates expressing OXA-58 carbapenemase in an intensive care unit.

OBJECTIVES: To investigate the resistance mechanisms and the genetic relationship of imipenem-resistant Acinetobacter baumannii isolates recovered in the intensive care unit (ICU) of a tertiary care hospital. METHODS: Imipenem-resistant A. baumannii clinical and environmental isolates were collected in the ICU of the Red Cross General Hospital, Athens, Greece between March and October 2002. The isolates were tested by Etest MBL, PCR, RT-PCR and sequencing for carbapenemase-encoding genes, PFGE and synergy experiments using meropenem and the efflux pump inhibitor carbonyl cyanide chlorophenylhydrazone. RESULTS: During the study period, 15 clinical and two environmental imipenem-resistant (MIC 8 to >128 mg/L) A. baumannii isolates were recovered. PFGE showed six different clones that included both clinical and environmental isolates. All 17 isolates were negative by Etest MBL and PCR for genes bla(IMP), bla(VIM), bla(SPM), bla(OXA-23-like) and bla(OXA-24-like). Genes bla(OXA-51-like) and bla(OXA-58-like) were amplified from 15 and 14 isolates, respectively. Sequencing of bla(OXA-51-like) amplicons identified bla(OXA-66) (nine cases) and bla(OXA-69) (six cases), whereas bla(OXA-58-like) sequences were classical bla(OXA-58). Reverse transcriptase-PCR showed that bla(OXA-51-like) genes were expressed in 12 and bla(OXA-58) in 10 isolates; in these isolates, inhibition of OXA enzymes by 200 mM of NaCl reduced carbapenem MICs by up to 4-fold. Overexpression of proton-gradient dependent efflux pumps did not contribute to carbapenem resistance in any isolate. Similarly, although AmpC expression was demonstrated in eight isolates, inhibition of AmpC with cloxacillin did not reduce the MICs of carbapenems significantly. CONCLUSIONS: These findings indicate wide dissemination of OXA-58 carbapenemase, which contributes, at least partially, to the imipenem resistance of unrelated A. baumannii isolates in our ICU.

Acinetobacter Infections↗

In vitro activity of temocillin against extended spectrum beta-lactamase-producing Escherichia coli.

OBJECTIVES: Temocillin is a semi-synthetic 6-alpha-methoxy derivative of ticarcillin. It is highly stable to most bacterial beta-lactamases. However, data concerning its activity against extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae are limited. We have analysed the in vitro activity of temocillin against clinical isolates of ESBL-producing Escherichia coli over the past 4 years in a university hospital in Brussels, Belgium. METHODS: Strains were screened for ESBL production using the double-disc synergy test. The MIC of 12 antimicrobial agents was determined for ESBL-producing E. coli isolates (n = 162) using the agar dilution method. ESBLs were characterized by isoelectric focusing; multiplex PCR for bla genes of the SHV, TEM and CTX-M families; and DNA sequencing. RESULTS: ESBL-producing E. coli isolates harboured CTX-M+TEM (35%), TEM alone (44%), CTX-M alone (6%), CTX-M+SHV (2%) and other ESBL combinations (10%). The proportion of temocillin-susceptible isolates was 92%, with MIC(50) and MIC(90) values of 8 and 32 mg/L, respectively. Co-resistance to ciprofloxacin and co-trimoxazole in ESBL-producing E. coli was frequent (39%). The proportion of isolates not susceptible to aminoglycosides was 55, 37 and 4% for tobramycin, gentamicin and amikacin, respectively. The proportion of isolates not susceptible to ceftazidime, cefotaxime, cefepime and piperacillin/tazobactam was 70, 52, 37 and 11%, respectively. No resistance to meropenem was observed. The proportion of strains exhibiting resistance to temocillin by year was stable over the study period. CONCLUSIONS: These data indicate good in vitro activity of temocillin against multiresistant ESBL-producing E. coli. Prospective clinical studies are necessary to examine temocillin's potential role in the treatment of non-complicated infections caused by ESBL-producing E. coli.

Anti-Bacterial Agents↗

Antimicrobial susceptibility of anaerobic bacteria in New Zealand: 1999-2003.

OBJECTIVES: Routine susceptibility testing of all anaerobic organisms is not advocated, but it is useful for laboratories to test periodically for anaerobic organisms and provide local susceptibility data to guide therapy. This study reports the national trend of antibiotic susceptibility of clinically significant anaerobes in New Zealand. METHODS: Clinical isolates were tested using standardized methods against a range of antibiotics commonly used to treat anaerobic infections. Susceptibility was determined using NCCLS criteria. The change in susceptibility trends between this study and earlier studies was measured by comparing the geometric mean of the MIC. RESULTS: A total of 364 anaerobes were tested. Penicillin had poor activity against Bacteroides spp., Prevotella spp., Eubacterium spp., Clostridium tertium and Veillonella spp. In general, Fusobacterium spp., Bacteroides ureolyticus, Propionibacterium spp., Clostridium perfringens and anaerobic streptococci isolates, with the exception of Peptostreptococcus anaerobius, were penicillin susceptible. Amoxicillin/clavulanate showed good activity against most anaerobes, but resistance was seen with Bacteroides fragilis group and P. anaerobius isolates. Cefoxitin was more active than cefotetan, particularly against non-B. fragilis species, Eubacterium spp. and P. anaerobius. Meropenem and imipenem showed good activity against all anaerobes, with only 2 and 4% of Bacteroides spp., respectively, showing resistance. With the exception of Propionibacterium acnes isolates, which are predictably resistant, metronidazole was active against all anaerobes tested. There has been little change in susceptibility since 1997. CONCLUSIONS: Metronidazole, cefoxitin, piperacillin/tazobactam and amoxicillin/clavulanate remain good empirical choices when anaerobes are expected in our setting. No clinically relevant changes in susceptibility over time were found.

Anti-Bacterial Agents↗

Evolution of multidrug-resistant Acinetobacter baumannii isolates obtained from elderly patients with respiratory tract infections.

OBJECTIVES: To study the evolution between 1999 and 2002 and mechanisms of antibiotic resistance in a multidrug-resistant Acinetobacter baumannii clone predominant in isolates from elderly patients with respiratory tract infections. METHODS: Susceptibility to antimicrobials was determined using an agar dilution method. Bacterial clones were identified by PCR-fingerprinting and PFGE with ApaI. Carbapenemases were detected by phenotypic tests; by PCR with primers specific for bla (OXA-40), bla(IMP), bla(VIM-1) and bla(VIM-2); and by hybridization with DNA probes. Class 1 integrons were detected using PCR. RESULTS: In 1999 isolates were grouped into two main genotypes: clone I (33%) and clone II (55%). These were also detected in 2002 with a different distribution: clone I (69%), clone II (22%). Resistance to amikacin, meropenem and imipenem increased significantly in clone I over this time, whereas clone II was not affected. In 2002, the incidence of bla(OXA-40) rose to 91% in clone I isolates with some also harbouring bla(VIM-2) and bla(IMP) genes. Different class 1 integrons were detected ranging in size from 550 to 1200 bp. No relationship was found between carbapenemases and class 1 integrons. CONCLUSIONS: In elderly patients, a single clone became predominant among A. baumannii isolates, coinciding with an increase in antibiotic resistance rates. The majority of isolates harboured the bla(OXA-40) carbapenemase gene and some of them also harboured bla(VIM-2) and bla(IMP) genes. The presence of class 1 integrons also increased over time.

Acinetobacter Infections↗

Emergence of PER and VEB extended-spectrum beta-lactamases in Acinetobacter baumannii in Belgium.

OBJECTIVES: Strains of Acinetobacter baumannii producing the extended-spectrum beta-lactamase (ESBL) PER-1 are widespread in Turkey and have also been reported from Korea and France. In contrast, A. baumannii producing the ESBL VEB-1 have only been reported from France, where one strain was responsible for a nationwide outbreak in 2003-2004. Here we describe the emergence of strains of A. baumannii producing VEB-1 and PER- 1 in Belgium. METHODS: Belgian hospitals were alerted in December 2003 to the emergence in France of VEB-1-producing A. baumannii susceptible only to meropenem and colistin. Isolates with a compatible susceptibility profile were sent to a single central laboratory for VEB-1 confirmation, molecular characterization and typing. RESULTS: From December 2003 to March 2005, three hospitals located close to the French border and one in the Brussels area reported isolation of eight A. baumannii isolates compatible with the French epidemic clone. Using PCR, six were identified as VEB-1-positive and two as PER-1-positive. All the VEB-1-positive isolates were clonally related by PFGE and by integron analysis to the French epidemic strain. The PER-1-positive strains were indistinguishable by PFGE but not related to the known French isolate or to several Turkish isolates. Both genes were chromosomally encoded. CONCLUSIONS: This work illustrates the inter-country spread of VEB-1-producing A. baumannii isolates as well as the emergence of PER-1-producing A. baumannii strains in Belgium.

Acinetobacter Infections↗

Treatment of ESBL-producing Klebsiella pneumoniae bacteraemia with carbapenems or flomoxef: a retrospective study and laboratory analysis of the isolates.

OBJECTIVES: To better understand the clinical outcomes of patients with extended-spectrum beta-lactamase-producing Klebsiella pneumoniae (ESBL-KP) bacteraemia treated with either flomoxef or a carbapenem, and to evaluate the in vitro activities of these antibiotics against ESBL-KP. METHODS: Retrospective analyses to identify risk factors for mortality in patients with flomoxef-susceptible ESBL-KP, especially addressing the therapeutic roles of flomoxef and carbapenem. In vitro activities of flomoxef and carbapenem against flomoxef-susceptible ESBL-KP isolates were evaluated by susceptibility testing and time-kill study. RESULTS: Twenty-seven patients (flomoxef group, n=7; carbapenem group, n=20) were included. Clinical severity reflected by high Pitt bacteraemia score (>or=6) was an independent risk factor for mortality (OR 13.43; 95% CI, 1.08-166.73; P=0.043), while use of flomoxef or a carbapenem was not. The MICs of flomoxef and carbapenem indicated that the tested ESBL-KP were susceptible to these antibiotics regardless of the inoculum size of 10(5) or 10(7) cfu/mL. Time-kill study showed that these antibiotics (flomoxef 8 mg/L and meropenem 4 mg/L) each acted actively against and inhibited the regrowth of the tested ESBL-KP for at least 24 h. CONCLUSIONS: Flomoxef might be as clinically effective as a carbapenem in treating flomoxef-susceptible ESBL-KP bacteraemia.

Adolescent↗

Third Belgian multicentre survey of antibiotic susceptibility of anaerobic bacteria.

OBJECTIVES: To collect recent data on the susceptibility of anaerobes and to compare them with results from previous studies. METHODS: Four hundred and forty-three anaerobic clinical isolates from various body sites were prospectively collected from October 2003 to February 2005 in nine Belgian hospitals. MICs were determined for nine anti-anaerobic and three recently developed antibiotics. RESULTS: Most gram-negative bacilli except Fusobacterium spp. were resistant to penicillin. Piperacillin/tazobactam, metronidazole, chloramphenicol, meropenem and amoxicillin/clavulanic acid were very active against all groups, but only 86% of Bacteroides fragilis group strains were susceptible to the latter. Cefoxitin, cefotetan and clindamycin were less active. In particular, only 62%, 52% and 48% of B. fragilis group strains were susceptible, respectively. Clindamycin shows a continuing decrease in activity, as 83% were still susceptible in 1987 and 66% in 1993-94. Anti-anaerobic activity of the new antibiotics is interesting, with MIC50 and MIC90 of 1 and >32 mg/L for moxifloxacin, 2 and 4 mg/L for linezolid and 0.5 and 8 mg/L for tigecycline. CONCLUSIONS: The susceptibility of anaerobic bacteria remains stable in Belgium, except for clindamycin, which shows a continuous decrease in activity. However, for each of the tested antibiotics, at least a few resistant organisms were detected. Consequently, for severe infections involving anaerobic bacteria, it could be advisable to perform microbiological testing instead of relying on known susceptibility profiles. Periodically monitoring background susceptibility remains necessary to guide empirical therapy.

Amoxicillin-Potassium Clavulanate Combination↗

Primary Whipple's disease of the brain: characterization of the clinical syndrome and molecular diagnosis.

BACKGROUND: Whipple's disease (WD) of the brain without evidence of systemic involvement is a rare illness that is difficult to recognize and potentially life-threatening. AIM: To elucidate the clinical features and diagnosis of primary WD of the brain. DESIGN: A single case study, with review of published data. METHODS: We linked the information about our patient with 956 citations to published WD material. We were able to identify 19 other patients with primary WD of the brain. RESULTS: Our patient was a 48-year-old woman who presented 2 years ago with generalized tonic/clonic seizures. WD of the brain was diagnosed after a life-threatening subacute deterioration leading to reduced consciousness and eye movement abnormalities. She had atrophy and gliosis of the right hippocampal formation, and nodular enhanc-ing lesions. She developed the syndrome of inappropriate ADH secretion, blepharospasm with a complete paralysis of vertical gaze, a severe amnesic syndrome, obstructive sleep apnoea, altered sleep physiology and CSF oligoclonal bands. Primary WD of the brain was diagnosed after PCR confirmed Tropheryma whipplei DNA in CSF and blood. She recovered after intravenous methylprednisolone, meropenem and cotrimoxazole. She has now survived for 24 months, lives independently and drives. Comparing our patient with the 19 others, two clinical syndromes were apparent, in both adults and children: (i) multifarious neurological symptoms and signs with a CT or MRI showing multiple nodular enhancing lesions; (ii) focal neurology secondary to solitary mass lesions. DISCUSSION: Primary WD of the brain may be diagnosed by recognition of these two clinical syndromes, and confirmed by the application of molecular biological techniques such as PCR.

Brain Diseases↗

One year study of bacterial and fungal nosocomial infections among patients in pediatric intensive care unit (PICU) in Alexandria.

UNLABELLED: A 1-year prospective and observational study included all admissions (n=216) until 48 h after discharge to Alexandria PICU between first of May 2003 and end of April 2004. Cultures for bacteria and fungi and antibiotic sensitivity tests (19 antibiotic using Bauer-Kirby disc diffusion method) were obtained (blood, stool, urine and cerebrospinal fluid, if needed) and repeated on suspicion of NIs. All cannulae, endotracheal tube (ET) aspirates and tips, nasogastric tubes and different catheters were cultured. All PICU health care workers (HCWs) were subjected to throat and under-finger nails cultures as well as inanimate objects, both on bimonthly basis. The referral place (ward or emergency), PRISM III score, length of stay (LOS) and fate were recorded. Amongst those patients whose age ranged from 1 to 23 months, 23 per cent had NIs with infection rates of 40/1000 days. Significantly high rates of mortality, LOS and PRISM III score were encountered among patients with NIs (52 per cent vs 30 per cent; 9.4+/-4.8 vs 5.4+/-2.2 days; 14.4+/-7 vs 11.8+/-6 respectively). The descending order of frequency of NIs was blood stream infection (BSI) (47 per cent), urinary tract infection (UTI) (28 per cent), ventilator-associated pneumonia (VAP) (16 per cent) and meningitis (9 per cent). Gr-ve bacilli accounted for 76.7 per cent; Gr+ve cocci 13.3 per cent (with satisfactory sensitivity to cefepime, imipenem and meropenem) and Candida albicans 10 per cent of all NIs. The rate of NIs/1000 device days were: 18.7 per cent for BSI, 10.9 per cent for VAP and 25.5 per cent for UTI. Vulnerable age groups were >6 m for VAP and <6 m for meningitis. Multiple logistic regression analysis identified LOS, PRISM III score and referral from wards a predictors of NI acquisition (odd ratio and 95 per cent confidence interval: 1.537, 1.423-1.659; 1.073, 1.041-1.105 and 0.269, 0.178-0.406 respectively). Bimonthly cultures for HCWs isolated coagulase-ve Staphylococci, while inanimate objects isolated diphtheroids and Candida albicans. CONCLUSION: NIs rate was high (23 per cent) mainly due to severity of condition on admission as shown by high PRISM III score value, the high PRISM III score, LOS and referral from wards were predictors of acquisition of NIs and there is a high incidence of Candida albicans infection (10 per cent of NIs).

Bacterial Infections↗

Melioidosis.

Melioidosis is an important public health problem in some regions, and a potential bioweapon. Recent reports confirm that it is endemic in China, Taiwan and Laos, but the true incidence in most countries is unknown, and the ecology poorly understood. Potable water was the source of two recent outbreaks. The epidemiology and clinical manifestations of the disease in Australia are similar to those in Thailand, although prostatic abscesses and neurological manifestations are more common and parotid abscesses less so. Mycotic aneurysms are not uncommon. Patients with cystic fibrosis are at risk of pulmonary melioidosis. Comparison with the avirulent Burkholderia thailandensis has identified capsular polysaccharide as an important virulence determinant in Burkholderia pseudomallei. Diagnosis still relies on culture, and a throat swab is a worthwhile sample. Several beta-lactams, such as meropenem, reduce the mortality, and long courses of cotrimoxazole-containing regimes are needed to prevent relapse. The value of adjunctive treatments, such as granulocyte colony-stimulating factor, warrants further evaluation.

Anti-Bacterial Agents↗

Comparison of antimicrobial cycling and mixing strategies in two medical intensive care units.

OBJECTIVE: To compare a mixing vs. a cycling strategy of use of anti-Pseudomonas antibiotics on the acquisition of resistant Gram-negative bacilli in the critical care setting. DESIGN: Prospective, open, comparative study of two strategies of antibiotic use. SETTING: Two medical intensive care units of a university hospital. PATIENTS: A total of 346 patients admitted for >or=48 hrs to two separate medical intensive care units during an 8-month period. INTERVENTIONS: Patients, who according to the attending physician's judgment required an anti-Pseudomonas regimen, were assigned to receive cefepime/ceftazidime, ciprofloxacin, a carbapemen, or piperacillin-tazobactam in this order. "Cycling" was accomplished by prescribing one of these antibiotics during 1 month each. "Mixing" was accomplished by using the same order of antibiotic administration on consecutive patients. Interventions were carried out during two successive 4-month periods, starting with mixing in one unit and cycling in the other. MEASUREMENTS AND MAIN RESULTS: Swabbing of nares, pharynx, and rectum and culture of respiratory secretions were obtained thrice weekly. The main outcome variable was the proportion of patients acquiring enteric or nonfermentative Gram-negative bacilli resistant to the antibiotics under intervention. The scheduled cycling of antibiotics was only partially successful. Although the expected antibiotic was the most prevalent anti-Pseudomonas agent used within the corresponding period, it never accounted for >45% of all anti-Pseudomonas antimicrobials administered. During mixing, a significantly higher proportion of patients acquired a strain of Pseudomonas aeruginosa resistant to cefepime (9% vs. 3%, p = .01), and there was a trend toward a more frequent acquisition of resistance to ceftazidime (p = .06), imipenem (p = .06), and meropenem (p = .07). No differences in the rate of acquisition of potentially resistant Gram-negative bacilli or incidence of intensive care unit-acquired infections and infections due to particular organisms were observed. CONCLUSIONS: In critically ill medical patients, a strategy of monthly rotation of anti-Pseudomonas beta-lactams and ciprofloxacin may perform better than a strategy of mixing in the acquisition of P. aeruginosa resistant to selected beta-lactams.

APACHE↗

Septic arthritis secondary to fusobacterium necrophorum in a 4-year-old girl: case report and review of the literature.

We report an unusual case of septic arthritis in a 4-year-old child caused by Fusobacterium necrophorum. In spite of aggressive parenteral antibiotic therapy with ampicillin-sulbactam after surgical drainage, disease recurred, requiring additional arthrotomies. The infection was eventually eradicated with parenteral meropenem and clindamycin, and additional surgical drainage.

Ampicillin↗

Carbapenems as inhibitors of OXA-13, a novel, integron-encoded beta-lactamase in Pseudomonas aeruginosa.

A clinical Pseudomonas aeruginosa strain, PAe391, was found to be resistant to a number of antibiotics including ticarcillin, piperacillin, cefsulodin and amikacin, and a disk diffusion assay showed evidence of pronounced synergy between imipenem and various beta-lactam antibiotics. Cloning and nucleotide sequence analysis revealed the dicistronic arrangement of an aac(6')-Ib variant and a novel blaOXA-type gene between the intI and qacE delta 1 genes typical of integrons, in PAe391, this integron was apparently chromosome-borne. The beta-lactamase, named OXA-13, displayed nine amino acid changes with respect to OXA-10:I in position 10 of OXA-10 to T (I10T), G20S, D55N, N73S, T107S, Y174F, E229G, S245N and E259A, OXA-13 (pIapp = 8.0) showed poor catalytic activity against penicillins as well as cephalosporins, but was efficient in hydrolysing some penicillinase-resistant beta-lactams, such as cefotaxime and aztreonam. It was efficiently inhibited by imipenem (KIapp = 11 nM), and formed a stable complex. While the KIapp value of meropenem was similar (16 nM), the corresponding complex was less stable.

Anti-Bacterial Agents↗

Type characterisation and antibiotic susceptibility of Burkholderia (Pseudomonas) cepacia isolates from patients with cystic fibrosis in the United Kingdom and the Republic of Ireland.

The spread of Burkholderia cepacia among cystic fibrosis (CF) patients in the UK prompted an investigation into whether an epidemic strain was responsible. A total of 366 B. cepacia isolates from 178 CF patients in 17 centres was examined by ribotyping and pulsed-field gel electrophoresis (PFGE). Associations were also sought between antibiotic resistance and strain type. More than 50 ribotype patterns were found but one, termed ribotype 1, was identified from 68 patients in eight centres. One centre had a single patient with this type while, in others, most or all patients harboured this organism. Small clusters of apparent cross-colonisation within centres were also evident for some other ribotypes. PFGE confirmed that ribotype 1 isolates were genetically similar. Ribotype 1 isolates were not markedly more resistant to antimicrobial agents than were other isolates, and the MICs of individual antibiotics were no more tightly clustered for ribotype 1 isolates than for others. Most isolates were resistant to ciprofloxacin, amikacin, gentamicin, tobramycin, carbenicillin, cefuroxime, cefotaxime, imipenem, biapenem, chloramphenicol, tetracycline, trimethoprim and sulphamethoxazole, but > or = 77% were susceptible to ceftazidime, piperacillin, piperacillin/ tazobactam and meropenem. We conclude that numerous strains of B. cepacia colonise CF patients in the UK and Ireland but that one epidemic strain has spread in at least eight centres. Isolates of this strain appear homogenous in total genomic profile but very variable in antibiotic susceptibility.

Bacterial Typing Techniques↗

Typing and characterization of carbapenem-resistant Acinetobacter calcoaceticus-baumannii complex in a Chinese hospital.

This study was designed to investigate the prevalence of carbapenem-resistant Acinetobacter calcoaceticus-baumannii complex (Acb complex) and to type carbapenemases. The relatedness of 45 isolates of carbapenem-resistant Acb complex collected from a clinical setting was analysed by PFGE. The carbapenemases produced by these isolates were typed by IEF, a three-dimensional test, 2-mercaptopropanoic acid inhibition assay, PCR and DNA cloning and sequencing. Results showed that all 45 isolates were resistant to multiple antibiotics including meropenem. The resistance rates to cefoperazone/sulbactam and ampicillin/sulbactam were 2.2 and 6.5%, respectively. About 71.7-78.3% of these isolates were intermediately resistant to cefepime, ceftazidime and cefotaxime. Forty-five isolates were classified into type A (98%) and B (2%) based on their PFGE patterns. Most of type A isolates were from the ICU. Type A was the dominant isolate, including subtypes A1 (22%), A2 (71%), A3 (2%) and A4 (2%). Only one isolate, from the haematology department, belonged to type B. Forty-three isolates (96%) were positive for carbapenemase. One isolate had two bands by IEF, the pIs of which were 6.64 and 7.17. The band with the pI of 6.64 was OXA-23. The other 42 isolates produced two bands with pIs of 6.40 and 7.01 which could not be inhibited by clavulanic acid, cloxacillin or 2-mercaptopropanoic acid. It can be concluded that the prevalent carbapenem-resistant Acb complex isolates from this hospital all had similar beta-lactamase patterns.

Acinetobacter Infections↗

Successfully treated spondylodiscitis due to a previously unreported mycobacterium.

A non-tuberculous mycobacterium was isolated, following a vertebral needle aspiration, from the blood of a patient with severe spondylodiscitis. The strain turned out to be different from any known mycobacterial species and was quite drug-susceptible in vitro. The patient improved markedly following treatment with meropenem, clarithromycin and amikacin.

Antitubercular Agents↗

Ascites in infants with severe sepsis - treatment with peritoneal drainage.

BACKGROUND: Ascites in neonates and infants is usually caused by cardiac failure and urinary or biliary tract obstruction. The objective of this study was to characterize our experience with ascites as a complication of sepsis. METHODS: We retrospectively collected and analyzed data of patients treated in the intensive care unit (ICU) of the university-based children's hospital, in whom ascites developed during nosocomial sepsis. Ten infants admitted to the ICU in the first 2 days of life developed sepsis on the mean 31.5 (+/-21.9) postnatal day. Gram-negative bacteria were the causative organism in nine cases, and Staphylococcus hemolyticus in one. Because of sepsis, reintubation and mechanical ventilation were necessary. All patients received broad spectrum antibiotics (including meropenem and ciprofloxacin), blood transfusions, catecholamines and intravenous immunoglobulin preparations. Ascites was observed on the median 13.5 day of sepsis (range 3-36), and severely compromised gas exchange. Continuous peritoneal drainage was applied by means of an intravascular catheter placed in the right lower abdominal quadrant. RESULTS: The mean drained fluid volume was 44.7 (+/-20.4) ml.kg(-1).day(-1), drainage was continued for a median of 5.5 (range 1-56) day, and enabled significant reduction of ventilator settings 24 h after its implementation. No severe complications related to drainage occurred; six of 10 babies survived. CONCLUSIONS: Ascites can develop in infants with sepsis and cause respiratory compromise. Continuous drainage of ascitic fluid by means of an intravenous catheter is relatively safe and can improve gas exchange.

Anti-Bacterial Agents↗