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1.  Treatment of Adult Femoral Shaft Fractures Using the Perkins Traction at Addis Ababa Tikur Anbessa University Hospital: The Ethiopian Experience 
International Surgery  2012;97(1):78-85.
This is a prospective study to evaluate the efficacy of the Perkins traction in the treatment of adult femoral shaft fractures from October 1, 2007, to the present at the Black Lion Hospital in Addis Ababa University Hospital in Ethiopia. All femur fractures admitted to the hospital were reviewed and evaluated for treatment. Black Lion Hospital (Tikur Anbessa) is the university hospital in Addis Ababa and the highest tertiary teaching hospital in a country of 85 million inhabitants. A 67-bed orthopedic department offers the main ground for teaching to the undergraduate medical students. The hospital is also the pivotal center for the formation of the orthopedic residents. Patients from different parts of the country are referred to this institution for orthopedic care. A total of 68 adult (older than 16 years) patients with 69 femoral shaft fractures were considered for treatment during the study period. Consent was obtained and prospective treatment initiated. A standard Perkins traction was applied by an orthopedic team composed of consultants, orthopedic residents, physical therapists, and nurses. A protocol was developed for patients undergoing such traction. The physiotherapists will supervise all individual or group therapy sessions. Progressive knee range of motion to facilitate quadriceps and hamstring muscle strengthening exercises were implemented four times a day and recorded. Demographic information, fracture patterns, duration of traction, thigh circumference leg length discrepancy, and pin sites were routinely monitored and charted. Data were computerized and analyzed weekly, and appropriate adjustments were made accordingly. Clinical evidence of a competent callus and confirmation by radiographic studies will influence the cessation of traction to allow gait training with toe-touch crutch ambulation. Progress will be monitored during the following outpatient visits in the fracture clinic. A total of 68 consecutive patients with 69 femoral shaft fractures were treated with the Perkins traction. There were 60 men (88.2%) and only 8 women (11.8%), for a ratio of 8 men to 1 woman. The age of the cohort patient varied between 18 and 28 years. The mechanisms of injury for most of the fractures were motor vehicle accidents, resulting in an isolated femoral shaft fracture in 49.2% of the patients. Half of the fractures were by means of closed injury (n  =  44; 64.7%). One patient with a bilateral femoral shaft fracture was also added to the study. The right side was more often involved, with 41 fractures (60%), than the left, with 28 fractures (40%). Most of the fractures involved the proximal third of the femur (n  =  34; 50%), but the most common fracture pattern was transverse (n  =  29; 42.6%), followed by a comminuted pattern (n  =  18; 26.5%). Three segmental fractures were also encountered. The mean hospital stay was 45 days (33 patients; 48.5%), with the length of time in traction varying from 30 to 40 days. Only 2 patients remained in traction for a period of 60 days. At the end of the traction period, 8 patients (11.8%) showed a decrease in the quadriceps mass, and 7 patients (10.3%) showed stiffness of the knee with a range of motion limited to 0° to 90°. Most patients were discharged after about 8 months of treatment. One patient suffered a nonunion, and one was malunited. Superficial pin care infections were noted in 8 patients (11.8%) and treated appropriately. The conservative treatment of 69 femoral shaft fractures using the Perkins traction at Black Lion University Hospital in Addis Ababa, Ethiopia, has been proven to be a safe and effective method. It should be encouraged in countries like ours where it is a luxury to have a C-Arm in the operating room and where the hardware often is not available to perform a stable stabilization of the long bone fractures.
PMCID: PMC3723198  PMID: 23343307
Perkins traction; Femoral shaft fracture; Conservative treatment; Quadriceps and hamstring exercises
2.  In vitro activity and beta-lactamase stability of a new monobactam, B0-1165. 
B0-1165 is a 1-carboxy-1-cyclopropoxyamino,4-fluoromethyl monobactam. It inhibited the majority of Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Citrobacter diversus, Aeromonas hydrophila, Proteus mirabilis, Proteus vulgaris, Providencia rettgeri, Providencia stuartii, Yersinia enterocolitica, Haemophilus influenzae, Neisseria gonorrhoeae, and Salmonella and Shigella species at less than or equal to 0.125 microgram/ml. Overall, its in vitro activity was similar to that of aztreonam, cefotaxime, and ceftazidime, with minor differences in the MICs for individual isolates. Enterobacter species and Citrobacter freundii which were derepressed for beta-lactamase production and had higher MICs of aztreonam and ceftazidime had MICs that ranged from 4 to 32 micrograms/ml. B0-1165 had activity against Pseudomonas aeruginosa similar to that of aztreonam but lower than that of ceftazidime and carumonam. Pseudomonas maltophilia and other Pseudomonas species were resistant or had MICs of 32 micrograms/ml, as did Acinetobacter species. B0-1165 did not inhibit streptococcal, staphylococcal, or anaerobic species, such as Clostridium and Bacteroides species. B0-1165 was not hydrolyzed to any appreciable extent by common plasmid- and chromosomally Richmond-Sykes type 1a-, 1c-, and 1d-mediated beta-lactamases. It inhibited the Enterobacter cloacae P99 and inducible Pseudomonas aeruginosa beta-lactamases. B0-1165 was a poor inducer of beta-lactamase, but exposing E. cloacae and C. freundii to B0-1165 selected for resistant isolates. Overall, B0-1165 had in vitro properties similar to those of other monobactams currently available or under investigation.
PMCID: PMC174767  PMID: 3300528
3.  Hospital Bed Occupancy and HIV/AIDS in three Major Public Hospitals of Addis Ababa, Ethiopia 
In countries like Ethiopia where the spread of HIV infection is extensive, health services are faced with an increased demand for care. The most obvious reflection of this increased demand is through patient load, longer bed occupancy perhaps to the exclusion of patients with other ailments.
The purpose of this study was to describe the bed occupancy rate and the average length of stay of HIV/AIDS inpatients of three major public hospitals.
A Retrospective Cross-sectional study was conducted in three major hospitals of Addis Ababa namely Zewditu Memorial Hospital, Tikure Anbessa Hospital and Saint Paul’s Hospital from February to March 2004.
Of the total 453 sampled inpatients, 293 (65 %) were HIV positives. Over half (55.0%) were Males. The most affected age group was between 24 and 56 years. The majority (85.8%) were from Addis Ababa and over half (57.7%) was married. Housewives constituted about a quarter (26.3%) of all the admitted cases. The most common co-morbidities resulted in admission to the medical wards among the HIV-positive cases were Tuberculosis (73.0%) and jirovicii pneumonia (70.3%), and their occurrence was significantly higher among HIV+ than their counter parts (p=0.001). Although numbers of patients admitted in Tikur Anbesa hospital was more than Saint Paul’s and Zewditu Memorial hospitals (ZMH), the proportion of HIV positive cases admitted to ZMH however was higher (49.0%) than Tikur Anbessa (14.0%) and Saint Paul’s hospitals (18.0%). Likewise the number of inpatient days was also higher in ZMH (n=7765) than the other hospitals. The bed occupancy rate was however, higher in ZMH (53.0%) than Tikur Anbessa (12.0%) and Saint Paul’s (12.0%) hospitals.
One of the most obvious consequences of HIV/AIDS patients are the increased occupancy of hospitals beds suggesting that only 81.1 % of the beds are for all other afflictions in the hospitals. It appears that there is a lot of concern that patients with HIV are competing with the non-HIV infected patients in a resource limited areas. Home based care with community involvement and greater use made of existing community resources might be a response to the limitations of curative hospital-based care and treatment needs of many HIV/AIDS patients.
PMCID: PMC3615262  PMID: 23675193
HIV/AIDS; hospitals; bed occupancy; Addis Ababa
4.  In vitro activity and beta-lactamase stability of a new penem, CGP 31608. 
The in vitro activity of CGP 31608, a new penem, against aerobic and anaerobic organisms was evaluated and compared with those of other beta-lactams. CGP 31608 inhibited Escherichia coli, Klebsiella pneumoniae, K. oxytoca, Proteus mirabilis, Citrobacter diversus, and Salmonella, Shigella, Aeromonas, and Yersinia spp. with MICs for 50% of the strains (MIC50s) of 2 to 4 micrograms/ml and MIC90s of 4 micrograms/ml, compared with cefotaxime, ceftazidime, aztreonam, and imipenem MICs of less than 0.25 microgram/ml. MIC90s were 8 micrograms/ml for Enterobacter species and C. freundii, for which other agents had MICs of 32 micrograms/ml, except imipenem, which had equal activity. The MIC90 for Proteus vulgaris, Morganella morganii, Providencia stuartii, and Providencia rettgeri was 8 micrograms/ml, compared with less than 2 micrograms/ml shown by the other agents. Acinetobacter species resistant to other agents except imipenem were inhibited by 4 micrograms/ml, as were Pseudomonas aeruginosa, including piperacillin-, ceftazidime-, and gentamicin-resistant isolates. The MIC for P. cepacia, P. fluorescens, and P. acidovorans was less than or equal to 8 micrograms/ml, but that for P. maltophilia was greater than or equal to 128 micrograms/ml. Hemolytic streptococci A, B, C, G, and F were inhibited by less than 1 micrograms/ml, but the MIC for Streptococcus faecalis was greater than or equal to 32 micrograms/ml. MICs for Staphylococcus aureus methicillin-susceptible and -resistant strains were less than or equal to 1 microgram/ml, as were those for methicillin-susceptible and -resistant S. epidermidis. Bacteroides fragilis and Clostridium species and Fusobacterium spp. were inhibited by less than or equal to 4 micrograms/ml. CGP 31608 was not hydrolyzed by plasmid beta-lactamases TEM-1, TEM-2, SHV-1, PSE-1, OXA-2, PSE-4, or by S. aureus. Chromosomal beta-lactamases of type Ia in Enterobacter cloacae P99 and Morganella morganii, Ic in P. vulgaris, K-1 in K. oxytoca, and Id in P. aeruginosa also did not hydrolyze CGP 31608. It inhibited TEM-1, but the 50% inhibitory concentration was 14.2 micrograms/ml compared with 0.15 micrograms/ml for the P99 enzyme. CGP 31608 induced beta-lactamases in P. aeruginosa, E. cloacae, C. freundii and Providencia rettgeri, but there was no increase in MICs for the isolates and it did not select strains derepressed for beta-lactamase production. Synergy of CGP 31608 and gentamicin was found against 90% P. aeruginosa, 60% Enterobacter cloacae, and 50% Serratia marcescens strains. No synergy was found with rifampin. A postantibiotic effect was found against E. coli.
PMCID: PMC174777  PMID: 3496845
5.  Adherence to Antiretroviral Therapy and associated factors among HIV infected children in Ethiopia: unannounced home-based pill count versus caregivers’ report 
BMC Pediatrics  2013;13:132.
The introduction of Antiretroviral Therapy (ART) has brought a remarkable reduction in HIV-related mortality and morbidity both in adults and children living with HIV/AIDS. Adherence to ART is the key to the successful treatment of patients as well as containment of drug resistance. Studies based on caregivers’ report have shown that adherence to ART among children is generally good. However, subjective methods such as caregivers’ report are known to overestimate the level of adherence. This study determined the rate of adherence and its predictors using unannounced home-based pill count and compared the result with caregivers’ report in a tertiary referral hospital in Ethiopia.
A cross-sectional study was conducted between December 1, 2011 and January 30, 2012. The study participants were 210 children on ART and their caregivers attending pediatric ART clinic of Tikur Anbessa Hospital (TAH), Addis Ababa University. Caregivers were interviewed at the ART clinic using a structured questionnaire. Then, unannounced home-based pill count was done 7 days after the interview.
Caregiver-reported adherence in the past 7 days prior to interview was 93.3%. Estimated adherence using unannounced home-based pill count was found, however, to be 34.8%. On multivariate logistic regression model, children with married [aOR = 7.85 (95% CI: 2.11,29.13)] and widowed/divorced [aOR = 7.14 (95% CI: 2.00,25.46)] caregivers, those who were not aware of their HIV sero-status [aOR = 2.35 (95% CI:1.09, 5.06)], and those with baseline WHO clinical stage III/IV [OR = 3.18 (95% CI: 1.21, 8.40] were more likely to adhere to their ART treatment. On the other hand, children on d4T/3Tc/EFV combination [OR = 0.10 (95% CI: 0.02, 0.53)] were less likely to adhere to their treatment. Caregivers’ forgetfulness and child refusal to take medication were reported as the major reasons for missing doses.
The level of adherence based on unannounced home-based pill count was unacceptably low. Interventions are urgently needed to improve adherence to ART among children at TAH. Besides, a longitudinal study measuring adherence combined with clinical parameters (viral load and CD4 count) is needed to identify a simple and reliable measure of adherence in the study area.
PMCID: PMC3766076  PMID: 24229394
Children; HAART; Adherence; Home-based unannounced pill count; Ethiopia
6.  Alimentary Tract Bacteria Isolated and Identified with API-20E and Molecular Cloning Techniques from Australian Tropical Fruit Flies, Bactrocera cacuminata and B. tryoni  
Bacteria were isolated from the crop and midgut of field collected Bactrocera cacuminata (Hering) and Bactrocera tryoni (Froggatt) (Diptera: Tephritidae). Two methods were used, firstly isolation onto two types of bacteriological culture media (PYEA and TSA) and identification using the API-20E diagnostic kit, and secondly, analysis of samples using the 16S rRNA gene molecular diagnostic method. Using the API-20E method, 10 genera and 17 species of bacteria in the family Enterobacteriaceae were identified from cultures growing on the nutrient agar. The dominant species in both the crop and midgut were Citrobacter freundii, Enterobacter cloacae and Klebsiella oxytoca. Providencia rettgeri, Klebsiella pneumoniae ssp ozaenae and Serratia marcescens were isolated from B. tryoni only. Using the molecular cloning technique that is based on 16S rRNA gene sequences, five bacteria classes were dignosed — Alpha-, Beta-, Gamma- and Delta- Proteobacteria and Firmicutes — including five families, Leuconostocaceae, Enterococcaceae, Acetobacteriaceae, Comamonadaceae and Enterobacteriaceae. The bacteria affiliated with Firmicutes were found mainly in the crop while the Gammaproteobacteria, especially the family Enterobacteriaceae, was dominant in the midgut. This paper presents results from the first known application of molecular cloning techniques to study bacteria within tephritid species and the first record of Firmicutes bacteria in these flies.
PMCID: PMC3016917  PMID: 20883132
Bactrocera cacuminata; Bactrocera tryoni; PCR; 16S rRNA gene; Enterobacteriaceae; lactic acid bacteria
7.  Antibacterial activity of BMS-180680, a new catechol-containing monobactam. 
The in vitro activities of a new catechol-containing monobactam, BMS-180680 (SQ 84,100), were compared to those of aztreonam, ceftazidime, imipenem, piperacillin-tazobactam, ciprofloxacin, amikacin, and trimethoprim-sulfamethoxazole. BMS-180680 was often the most active compound against many species of the family Enterobacteriaceae, with MICs at which 90% of the isolates were inhibited (MIC90s) of < or = 0.5 microg/ml for Escherichia coli, Klebsiella spp., Citrobacter diversus, Enterobacter aerogenes, Serratia marcescens, Proteus spp., and Providencia spp. BMS-180680 had moderate activities (MIC90s of 2 to 8 microg/ml) against Citrobacter freundii, Morganella morganii, Shigella spp., and non-E. aerogenes Enterobacter spp. BMS-180680 was the only antibiotic evaluated that was active against >90% of the Pseudomonas aeruginosa (MIC90, 0.25 microg/ml), Burkholderia cepacia, and Stenotrophomonas maltophilia (MIC90s, 1 microg/ml) strains tested. BMS-180680 was inactive against most strains of Pseudomonas fluorescens, Pseudomonas stutzeri, Pseudomonas diminuta, and Burkholderia pickettii. BMS-180680 was moderately active (MIC90s of 4 to 8 microg/ml) against Alcaligenes spp. and Acinetobacter lwoffii and less active (MIC90, 16 microg/ml) against Acinetobacter calcoaceticus-Acinetobacter baumanii complex. BMS-180680 lacked activity against gram-positive bacteria and anaerobic bacteria. Both tonB and cir fiu double mutants of E. coli had greatly decreased susceptibility to BMS-180680. Of the TEM, PSE, and chromosomal-encoded beta-lactamases tested, only the K1 enzyme hydrolyzed BMS-180680 to any measurable extent. Like aztreonam, BMS-180680 bound preferentially to penicillin-binding protein 3. The MICs of BMS-180680 were not influenced by the presence of hematin or 5% sheep blood in the test medium or with incubation in an atmosphere containing 5% CO2. BMS-180680 MICs obtained under strict anaerobic conditions were significantly higher than those obtained in ambient air.
PMCID: PMC163842  PMID: 9145861
8.  In vitro activity and beta-lactamase stability of LJC 10,627. 
The in vitro activity of LJC 10,627, a new carbapenem, was compared with those of imipenem, cefotaxime, ceftazidime, and gentamicin. LJC 10,627 inhibited 90% of Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter aerogenes, Enterobacter agglomerans, Enterobacter cloacae, Hafnia alvei, Citrobacter freundii, Citrobacter diversus, Proteus mirabilis, Morganella morganii, Proteus rettgeri, Serratia marcescens, Pseudomonas cepacia, salmonellae, shigellae, aeromonas, and yersiniae at less than or equal to 2 micrograms/ml. Haemophilus influenzae was inhibited by 0.5 microgram/ml, and moraxellae were inhibited by 0.12 microgram/ml. LJC 10,627 was twofold more active than imipenem against aerobic gram-negative organisms and inhibited ceftazidime-, cefotaxime-, and gentamicin-resistant members of the genera Klebsiella, Enterobacter, Citrobacter, and Serratia at less than or equal to 2 micrograms/ml. Xanthomonas maltophilia strains were resistant to the drug. Imipenem was two- to fourfold more active than LJC 10,627 against Staphylococcus aureus and Staphylococcus epidermidis. LJC 10,627 did not inhibit most methicillin-resistant Staphylococcus aureus or methicillin-resistant Staphylococcus epidermidis strains. LJC 10,627 inhibited Streptococcus pyogenes and Streptococcus pneumoniae at 0.06 and 0.12 microgram/ml, respectively. Bacteroides fragilis and other Bacteroides spp. were inhibited by 0.5 microgram of LJC 10,627 per ml. Serum (50%) did not affect the MICs. LJC 10,627 was not hydrolyzed by plasmid-mediated beta-lactamases of Bush types 2b, 2b', TEM-1, TEM-2, TEM-3, TEM-5, TEM-7, TEM-9, and SHV-1; the chromosomal beta-lactamases of Bush type 1; P-99; a Morganella enzyme; or a Citrobacter freundii enzyme. The Bush type 2c and 2d enzymes OXA-1, OXA-2, PSE-1, PSE-2, and PSE-4 did not hydrolyze LJC 10,627, nor did the beta-lactamases of Staphylococcus aureus, Moraxella spp., Bacteroides fragilis, and Proteus vulgaris. The beta-lactamase of Xanthomonas hydrolyzed LJC 10,627, albeit at approximately one-third the rate that imipenem was hydrolyzed.
PMCID: PMC191596  PMID: 1510436
9.  Tigemonam, an oral monobactam. 
Tigemonam is an orally administered monobactam. At less than or equal to 1 microgram/ml it inhibited the majority of strains of Escherichia coli, Klebsiella spp., Enterobacter aerogenes, Citrobacter diversus, Proteus spp., Providencia spp., Aeromonas hydrophila, Salmonella spp., Shigella spp., Serratia marcescens, and Yersinia enterocolitica. At less than or equal to 0.25 microgram/ml it inhibited Haemophilus spp., Neisseria spp., and Branhamella catarrhalis. It did not inhibit Pseudomonas spp. or Acinetobacter spp. Tigemonam was more active than cephalexin and amoxicillin-clavulanate and inhibited many members of the family Enterobacteriaceae resistant to trimethoprim-sulfamethoxazole and gentamicin. Some Enterobacter cloacae and Citrobacter freundii strains resistant to aminothiazole iminomethoxy cephalosporins and aztreonam were resistant to tigemonam. The MIC for 90% of hemolytic streptococci of groups A, B, and C and for Streptococcus pneumoniae was 16 micrograms/ml, but the MIC for 90% of enterococci, Listeria spp., Bacteroides spp., and viridans group streptococci was greater than 64 micrograms/ml. Tigemonam was not hydrolyzed by the common plasmid beta-lactamases such as TEM-1 and SHV-1 or by the chromosomal beta-lactamases of Enterobacter, Morganella, Pseudomonas, and Bacteroides spp. Tigemonam inhibited beta-lactamases of E. cloacae and Pseudomonas aeruginosa but did not induce beta-lactamases. The growth medium had a minimal effect on the in vitro activity of tigemonam, and there was a close agreement between the MICs and MBCs.
PMCID: PMC172104  PMID: 3279906
10.  In vitro and in vivo antibacterial activities of CS-807, a new oral cephalosporin. 
CS-807 is a new oral prodrug of R-3746, a cephalosporin derivative, with potent in vitro and in vivo antibacterial activity against both gram-positive and gram-negative bacteria. The susceptibility of about 1,200 clinical isolates to R-3746 was determined by the agar dilution method. Ninety percent or more of pathogens such as Staphylococcus aureus, streptococci, Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, indole-positive and indole-negative Proteus spp., Providencia rettgeri, and Haemophilus influenzae were inhibited at concentrations ranging less than or equal to 0.01 to 1.56 micrograms/ml. Furthermore, at a concentration of 3.13 micrograms/ml, 50% or more of Staphylococcus epidermidis, Morganella morganii, Citrobacter freundii, and Serratia marcescens strains were also inhibited. Pseudomonas aeruginosa and Xanthomonas maltophilia were resistant to R-3746. The activity of R-3746 was scarcely influenced by several growth conditions. R-3746 was highly resistant to hydrolysis by beta-lactamases derived from various species of bacteria. Killing-curve studies demonstrated bactericidal activity of R-3746 at concentrations above the MIC. R-3746 showed high affinity for penicillin-binding proteins 1, 3, and 4 of Staphylococcus aureus and 1A, 1Bs, and 3 of Escherichia coli. Systemic infections in mice caused by various pathogens, including beta-lactamase-producing strains, responded well to therapy with oral doses of CS-807.
PMCID: PMC174876  PMID: 3310868
11.  In vitro activity and beta-lactamase stability of a new difluoro oxacephem, 6315-S. 
6315-S, a novel difluoromethyl thioacetamido oxacephem, had in vitro activity comparable to that of cefotaxime and moxalactam against Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Klebsiella oxytoca, Citrobacter diversus, Salmonella spp., and Shigella spp., inhibiting 90% at less than or equal to 0.25 microgram/ml. It inhibited piperacillin- and cefoperazone-resistant isolates in these species. 6315-S did not inhibit cefotaxime- or moxalactam-resistant Citrobacter freundii, Enterobacter aerogenes, or Enterobacter cloacae (MICs for 90% of the strains tested were greater than or equal to 16 micrograms/ml). Proteus vulgaris resistant to cefotaxime was inhibited. Pseudomonas species and Acinetobacter species were resistant (MICs greater than 64 micrograms/ml). MICs for 90% of the Staphylococcus aureus and S. epidermidis isolates were 4 micrograms/ml. 6315-S was highly active against anaerobic species of Clostridium, Fusobacterium, Bacteroides, and peptostreptococci and was superior to other agents against these organisms. 6315-S was not hydrolyzed by the major plasmid and chromosomal beta-lactamases, but it induced chromosomal beta-lactamases in Enterobacter cloacae and Pseudomonas aeruginosa.
PMCID: PMC176505  PMID: 3492172
12.  Antimicrobial Resistance among Gram-Negative Bacilli Causing Infections in Intensive Care Unit Patients in the United States between 1993 and 2004▿  
Journal of Clinical Microbiology  2007;45(10):3352-3359.
During the 12-year period from 1993 to 2004, antimicrobial susceptibility profiles of 74,394 gram-negative bacillus isolates recovered from intensive care unit (ICU) patients in United States hospitals were determined by participating hospitals and collected in a central location. MICs for 12 different agents were determined using a standardized broth microdilution method. The 11 organisms most frequently isolated were Pseudomonas aeruginosa (22.2%), Escherichia coli (18.8%), Klebsiella pneumoniae (14.2%), Enterobacter cloacae (9.1%), Acinetobacter spp. (6.2%), Serratia marcescens (5.5%), Enterobacter aerogenes (4.4%), Stenotrophomonas maltophilia (4.3%), Proteus mirabilis (4.0%), Klebsiella oxytoca (2.7%), and Citrobacter freundii (2.0%). Specimen sources included the lower respiratory tract (52.1%), urine (17.3%), and blood (14.2%). Rates of resistance to many of the antibiotics tested remained stable during the 12-year study period. Carbapenems were the most active drugs tested against most of the bacterial species. E. coli and P. mirabilis remained susceptible to most of the drugs tested. Mean rates of resistance to 9 of the 12 drugs tested increased with Acinetobacter spp. Rates of resistance to ciprofloxacin increased over the study period for most species. Ceftazidime was the only agent to which a number of species (Acinetobacter spp., C. freundii, E. aerogenes, K. pneumoniae, P. aeruginosa, and S. marcescens) became more susceptible. The prevalence of multidrug resistance, defined as resistance to at least one extended-spectrum cephalosporin, one aminoglycoside, and ciprofloxacin, increased substantially among ICU isolates of Acinetobacter spp., P. aeruginosa, K. pneumoniae, and E. cloacae.
PMCID: PMC2045364  PMID: 17715376
13.  Distribution of Extended-Spectrum β-Lactamases, AmpC β-Lactamases, and Carbapenemases among Enterobacteriaceae Isolates Causing Intra-Abdominal Infections in the Asia-Pacific Region: Results of the Study for Monitoring Antimicrobial Resistance Trends (SMART) 
The increasing trend of β-lactam resistance among Enterobacteriaceae is a worldwide threat. Enterobacteriaceae isolates causing intra-abdominal infections (IAI) from the Study for Monitoring Antimicrobial Resistance Trends (SMART) collected in 2008 and 2009 from the Asia-Pacific region were investigated. Detection of extended-spectrum β-lactamases (ESBLs), AmpC β-lactamases, and carbapenemases was performed by multiplex PCR. A total of 699 Enterobacteriaceae isolates with positive genotypic results, included Escherichia coli (n = 443), Klebsiella pneumoniae (n = 187), Enterobacter cloacae (n = 45), Klebsiella oxytoca (n = 9), Citrobacter freundii (n = 5), Proteus mirabilis (n = 3), Enterobacter aerogenes (n = 2), Morganella morganii (n = 2), and one each of Enterobacter asburiae, Proteus vulgaris, and Providencia rettgeri were analyzed. Nearly 20% of these β-lactamase-producing Enterobacteriaceae isolates were from community-associated IAI. CTX-M (588 isolates, including 428 [72.8%] with CTX-M-15) was the most common ESBL, followed by SHV (n = 59) and TEM (n = 4). CMY (n = 110, including 102 [92.7%] with CMY-2) was the most common AmpC β-lactamase, followed by DHA (n = 46) and ACT/MIR (n = 40). NDM (n = 65, including 62 [95.4%] with NDM-1) was the most common carbapenemase, followed by IMP (n = 7) and OXA (n = 7). Isolates from hospital-associated IAI had more complicated β-lactamase combinations than isolates from the community. Carbapenemases were all exclusively detected in Enterobacteriaceae isolates from India, except that IMP β-lactamases were also detected in Philippines and Australia. CTX-M β-lactamases were the predominant ESBLs produced by Enterobacteriaceae causing IAI in the Asia-Pacific region. Emergence of CTX-M-15-, CMY-2-, and NDM-1-producing Enterobacteriaceae isolates is of major concern and highlights the need for further surveillance in this area.
PMCID: PMC3697370  PMID: 23587958
14.  Comparative in vitro activity and beta-lactamase stability of FR 17027, a new orally active cephalosporin. 
FR 17027, a new orally absorbed cephalosporin ester, inhibited group A and B streptococci and Streptococcus pneumoniae at less than or equal to 0.1 micrograms/ml, which is similar to the inhibition concentration of amoxicillin and cefaclor, and was more active than cephalexin. It was less active (MIC, 25 micrograms/ml) against staphylococci than was cephalexin, and it did not inhibit Streptococcus faecalis or Listeria monocytogenes. FR 17027 inhibited beta-lactamase-producing isolates of Neisseria gonorrhoeae, Haemophilus influenzae, and Branhamella catarrhalis at less than 0.1 micrograms/ml and was more active than cefaclor or cephalexin against these bacteria. FR 17027 inhibited Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Klebsiella oxytoca, Providencia stuartii, Providencia rettgeri, and Citrobacter diversus at less than or equal to 1 microgram/ml, including isolated resistant to amoxicillin, cephalexin, and cefaclor, but it was less active than ceftizoxime. Some strains of Enterobacter cloacae, Enterobacter agglomerans, Citrobacter freundii, and Enterobacter aerogenes were resistant (MIC, greater than 25 micrograms/ml). FR 17027 did not inhibit Pseudomonas aeruginosa, other Pseudomonas species, Acinetobacter species, or Bacteroides species. Activity was minimally affected by growth conditions. FR 17027 was not hydrolyzed by the common beta-lactamases present in many of the pathogens causing respiratory and urinary tract infections in outpatients.
PMCID: PMC284114  PMID: 6333207
15.  In vitro activity of lomefloxacin (SC-47111; NY-198), a difluoroquinolone 3-carboxylic acid, compared with those of other quinolones. 
Lomefloxacin (SC-47111; NY-198) is a new difluoroquinolone agent. It inhibited 90% of Escherichia coli, Klebsiella spp., Enterobacter spp., Citrobacter spp., Proteus mirabilis, Morganella morganii, Proteus vulgaris, Serratia marcescens, Salmonella spp., Shigella spp., Aeromonas spp., Yersinia spp., Haemophilus influenzae, and Neisseria gonorrhoeae at less than or equal to 2 micrograms/ml. Lomefloxacin inhibited 90% of Pseudomonas aeruginosa at 4 micrograms/ml. Lomefloxacin was equal in activity to norfloxacin against Escherichia coli, Klebsiella spp., Enterobacter spp., Haemophilus influenzae, and Neisseria gonorrhoeae but was twofold less active against Proteus spp., Providencia spp., Serratia marcescens, Salmonella spp., and Shigella spp. Ofloxacin was generally 2- to 4-fold more active, and ciprofloxacin was 4- to 16-fold more active. Lomefloxacin inhibited Staphylococcus aureus, including methicillin-resistant isolates, but MICs for 90% of streptococcal species tested were 8 micrograms/ml. In the presence of 9 mM Mg2+, MICs for Escherichia coli, Klebsiella pneumoniae, Serratia marcescens, and Pseudomonas aeruginosa were increased, as they were when they were tested in urine. A single-step increase in resistance to eightfold above the MIC occurred at a frequency of less than 10(-10), but serial transfer of bacteria in the presence of the agent produced MIC increases. Lomefloxacin had activity and properties comparable to those of many of the new quinolones.
PMCID: PMC172248  PMID: 3164987
16.  Comparative in vitro activities of piperacillin-tazobactam and ticarcillin-clavulanate. 
The in vitro activities of ticarcillin, piperacillin, clavulanic acid, tazobactam, ticarcillin-clavulanate, and piperacillin-tazobactam against 819 bacterial isolates were compared. The two beta-lactamase inhibitors, clavulanic acid and tazobactam, had little useful antibacterial activity but enhanced the activities of the penicillins against beta-lactamase-producing strains of Haemophilus influenzae, Branhamella catarrhalis, and methicillin-susceptible Staphylococcus aureus; all strains were susceptible to both combinations. Both enzyme inhibitors also enhanced the activities of the penicillins against most strains of Escherichia coli, Klebsiella spp., Citrobacter diversus, Proteus spp., Providencia spp., and Bacteroides spp. and against occasional strains of Citrobacter freundii, Enterobacter spp., and Serratia marcescens. Clavulanic acid frequently enhanced the activity of ticarcillin against Xanthomonas maltophilia, and tazobactam frequently enhanced the activity of piperacillin against Morganella morganii. Enhancement was observed primarily with strains relatively resistant to the penicillins. In general, clavulanic acid was more effective than tazobactam in enhancing penicillin activity against Klebsiella spp., C. diversus, X. maltophilia, and Bacteroides spp., whereas tazobactam was more effective against Escherichia coli and Proteeae. There was little or no enhancement of activity against Enterococcus faecalis, Aeromonas hydrophila, Pseudomonas aeruginosa, Pseudomonas cepacia, or Acinetobacter anitratus. Clavulanic acid occasionally antagonized the activity of ticarcillin against ticarcillin-susceptible members of the family Enterobacteriaceae, but those strains were still considered susceptible to the combination. Tazobactam never antagonized the activity of piperacillin. In a direct comparison of the activities of ticarcillin-clavulanate and piperacillin-tazobactam, the two were equally active against H. influenzae, B. catarrhalis, and S. aureus; the latter was more active against E. faecalis. For relatively susceptible strains of members of the family Enterobacteriaceae, neither combination was predictably more active than the other, but relatively resistant strains were generally more susceptible to piperacillin-tazobactam. Piperacillin-tazobactam was more active than ticarcillin-clavulanate against A. hydrophila, P. aeruginosa, and P. cepacia, similar in activity against A. anitratus, and less active against X. maltophilia and Bacteroides spp.
PMCID: PMC172638  PMID: 2552904
17.  Isolation of Intestinal Parasites of Public Health Importance from Cockroaches (Blattella germanica) in Jimma Town, Southwestern Ethiopia 
Cockroaches are claimed to be mechanical transmitters of disease causing microorganisms such as intestinal parasites, bacteria, fungi, and viruses. This study assessed the potential of the German cockroach Blattella germanica in the mechanical transmission of intestinal parasites of public health importance. A total of 2010 cockroaches were collected from 404 households in Jimma Town, southwestern Ethiopia. All the collected cockroaches were identified to species as B. germanica. The contents of their gut and external body parts were examined for the presence of intestinal parasites. Overall, 152 (75.6%) of the 210 batches were found to harbor at least one species of human intestinal parasite. Ascaris lumbricoides, Trichuris trichiura, Taenia spp, Strongyloides-like parasite, Entamoeba histolytica/dispar/moshkovski, Giardia duodenalis and Balantidium coli were detected from gut contents. Moreover, parasites were also isolated from the external surface in 22 (10.95%) of the batches. There was significant difference in parasite carriage rate of the cockroaches among the study sites (P = 0.013). In conclusion, B. germanica was found to harbor intestinal parasites of public health importance. Hence, awareness on the potential role of cockroaches in the mechanical transmission of human intestinal parasites needs to be created. Moreover, further identification of the Strongyloides-like worm is required using molecular diagnostics.
PMCID: PMC3932213  PMID: 24649356
18.  Production of Cellulose and Curli Fimbriae by Members of the Family Enterobacteriaceae Isolated from the Human Gastrointestinal Tract  
Infection and Immunity  2003;71(7):4151-4158.
Citrobacter spp., Enterobacter spp., and Klebsiella spp. isolated from the human gut were investigated for the biosynthesis of cellulose and curli fimbriae (csg). While Citrobacter spp. produced curli fimbriae and cellulose and Enterobacter spp. produced cellulose with various temperature-regulatory programs, Klebsiella spp. did not show pronounced expression of those extracellular matrix components. Investigation of multicellular behavior in two Citrobacter species and Enterobacter sakazakii showed an extracellular matrix, cell clumping, pellicle formation, and biofilm formation associated with the expression of cellulose and curli fimbriae. In those three strains, the csgD-csgBA region and the cellulose synthase gene bcsA were conserved. PCR screening for the presence of csgD, csgA and bcsA revealed that besides Klebsiella pneumoniae and Klebsiella oxytoca, all species investigated harbored the genetic information for expression of curli fimbriae and cellulose. Since Citrobacter spp., Enterobacter spp., and Klebsiella spp. are frequently found to cause biofilm-related infections such as catheter-associated urinary tract infections, the human gut could serve as a reservoir for dissemination of biofilm-forming isolates.
PMCID: PMC162016  PMID: 12819107
19.  In vitro studies on the antibacterial activities of YM-13115, a new broad-spectrum cephalosporin. 
The in vitro antibacterial activities of YM-13115, a new parenteral cephalosporin, were compared with those of ceftazidime, cefoperazone, and cefsulodin. The compound was highly active against the common members of the Enterobacteriaceae and 2 to 256 times more active than cefoperazone. YM-13115 was as active as ceftazidime against Citrobacter freundii, Proteus vulgaris, and Morganella morganii and two to four times more active than ceftazidime against Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Enterobacter aerogenes, Serratia marcescens, Proteus mirabilis, Providencia rettgeri, and Providencia stuartii. The activity of YM-13115 against Pseudomonas aeruginosa (with MICs of 0.78 and 3.13 micrograms/ml for 50 and 90% of the isolates, respectively) was ca. 2 times that of ceftazidime, 4 times that of cefsulodin, and 16 times that of cefoperazone. Against Haemophilus influenzae YM-13115 was more active than ceftazidime. YM-13115 was less active than ceftazidime, cefoperazone, and cefsulodin against Staphylococcus aureus and Staphylococcus epidermidis. The concentrations of YM-13115 required to inhibit the growth of 90% of the isolates of Streptococcus pyogenes and Streptococcus pneumoniae were 0.78 and 1.56 microgram/ml, respectively, but concentrations above 100 micrograms/ml were required to inhibit Streptococcus faecalis. YM-13115 was not hydrolyzed by the common plasmid and chromosomal beta-lactamases. YM-13115 is extremely active against P. aeruginosa and members of the Enterobacteriaceae.
PMCID: PMC180096  PMID: 3890729
20.  In vitro activity of norfloxacin, a quinolinecarboxylic acid, compared with that of beta-lactams, aminoglycosides, and trimethoprim. 
Norfloxacin is a quinolinecarboxylic acid compound. We examined the in vitro activity of this compound against gram-positive and -negative species, including anaerobic species. It inhibited 90% (MIC90) of strains of Escherichia coli at 0.05 microgram/ml, Klebsiella sp. at 0.4 microgram/ml, Salmonella and Shigella spp. at 0.1 microgram/ml, Citrobacter sp. at 0.4 microgram/ml, Enterobacter cloacae at 0.2 microgram/ml, Enterobacter aerogenes at 0.4 microgram/ml, and Enterobacter agglomerans at 0.2 microgram/ml. The MICs of Proteus mirabilis, Morganella sp., Proteus vulgaris, Proteus rettgeri, and Providencia sp. were 0.1, 0.2, 0.8, 0.3, and 1.6 micrograms/ml, respectively. The MIC90 of Serratia sp. was 1.6 micrograms/ml, and that of Acinetobacter sp. was 6.3 micrograms/ml. For Pseudomonas aeruginosa the MIC50, the MIC75, and the MIC90 were 0.8, 1.6, and 3.1 micrograms/ml, respectively. The MIC50 of Pseudomonas maltophilia was 3.1 micrograms/ml, and the MIC90 was 12.5 micrograms/ml. Yersinia, Arizona, and Aeromonas all were inhibited at concentrations below 1 microgram/ml, as was Campylobacter. The activity of the compound against gram-positive species was less impressive: the MIC90s of Staphylococcus aureus, Streptococcus pyogenes, Streptococcus agalactiae, and Streptococcus faecalis were 1.6, 6.3, 3.1, and 12.5 micrograms/ml, respectively. All Listeria strains were inhibited by 3.1 micrograms/ml. The activity of norfloxacine was not affected by the type of medium, pH, or inoculum size. There was no major difference between MIC and minimum bactericidal concentration values. Norfloxacin inhibited bacteria in every species which was resistant to ampicillin, carbenicillin, cephalexin, gentamicin, and trimethoprim at concentrations lower than those of aminothiazolyl cephalosporins, moxalactam, and aminoglycosides.
PMCID: PMC183667  PMID: 6214995
21.  In vitro activity and beta-lactamase stability of GR69153, a new long-acting cephalosporin. 
GR69153, a new parenteral cephalosporin, inhibited 90% of Escherichia coli, Klebsiella oxytoca, Proteus mirabilis, Citrobacter diversus, shigellae, and salmonellae at less than 0.25 micrograms/ml (MIC90). It had activity comparable to those of ceftazidime, cefpirome, cefepime, and E-1040. Against cephalosporinase-producing Enterobacter cloacae, Citrobacter freundii, and Serratia marcescens, MICs ranged from 0.12 to greater than 32 micrograms/ml, and cefpirome and cefepime were the most active agents against these species. Pseudomonas aeruginosa was highly susceptible to GR69153, and for this organism the MIC90 was less than or equal to 2 micrograms/ml, which was similar to the E-1040 MIC90, but most Pseudomonas cepacia and Xanthomonas maltophilia isolates were resistant. GR69153 inhibited Haemophilus influenzae and Moraxella branhamella at less than or equal to 0.5 micrograms/ml. For Staphylococcus aureus GR69153 MICs were similar to those of ceftazidime and E-1040. Enterococci and listeriae were resistant to GR69153, but Streptococcus pyogenes and Streptococcus pneumoniae were inhibited by 0.5 micrograms/ml. The activity of GR69153 was not affected by serum. GR69153 was not inactivated by the beta-lactamases of Staphylococcus aureus, TEM-1, TEM-2, SHV-1, and BRO-1, but it was hydrolyzed by TEM-3, TEM-9, and morganellae. GR69153 had overall activity comparable to those of commercially available parenteral cephalosporins or those found in clinical investigations. It is more active against bacteroides than most available aminothiazolyl parenteral cephalosporins are. GR69153 is hydrolyzed by the new plasmid beta-lactamases, and thus, its primary value may be related to its pharmacological properties.
PMCID: PMC244988  PMID: 2024959
22.  Allergens in School Settings: Results of Environmental Assessments in 3 City School Systems 
The Journal of school health  2006;76(6):246-249.
Environmental allergens are major triggers for pediatric asthma. While children’s greatest exposure to indoor allergens is in the home, other public places where children spend a large amount of time, such as school and day care centers, may also be sources of significant allergen encounters. The purpose of this article is to describe schoolroom allergen levels from 3 different geographic sites obtained from dust samples collected in the, fall and in spring. Environmental dust samples were collected from elementary schools in Birmingham (AL), Detroit (MI), and Houston (TX), from 4 room locations, including the cafeteria, library, upper grades, and lower grades. Samples were assayed for dust mite (Dermatophagoides pteronyssinus and Dermatophagoides farinae), cat (Felis domesticus), and cockroach (Blatella germanica 2) allergen levels. Allergen levels varied by geographic location and type of schoolroom. Schoolroom settings differed by the type of flooring (hard and carpet), room characteristics and use (food service, library shelves with books, and general classroom with multiple types of materials [individual desks and different types of furniture]), and the average age of the schoolroom dwellers (younger vs older children). Dust mite, cat, and cockroach allergens were present in all schoolrooms and all sites at varying levels by season and by type of room. Schools may be important sources of direct allergen exposure and reservoirs that could potentially contribute to allergic sensitization and, disease exacerbation in. children. Further studies are needed to carefully examine the environmental allergen load in schools and its effect on children.
PMCID: PMC1599794  PMID: 16918848
23.  In vitro activity and beta-lactamase stability of two oral cephalosporins, ceftetrame (Ro 19-5247) and cefetamet (Ro 15-8074). 
Ceftetrame (Ro 19-5247) and cefetamet (Ro 15-8074), two new orally administered aminothiazolyl imimomethoxy cephalosporins, inhibited hemolytic streptococci and Streptococcus pneumoniae at less than or equal to 0.5 micrograms/ml but were less active against staphylococci than were cephalexin and cefaclor. They did not inhibit S. faecalis, S. faecium, Listeria monocytogenes, Corynebacterium JK species, or Pseudomonas aeruginosa. Haemophilus influenzae, Branhamella catarrhalis, and Neisseria gonorrhoeae, including ampicillin-resistant isolates, were inhibited at less than 0.25 micrograms/ml. Both agents inhibited Escherichia coli, Klebsiella pneumoniae, K. oxytoca, Proteus mirabilis, Salmonella species, Shigella species, Citrobacter diversus, and Aeromonas hydrophila resistant to ampicillin, cephalexin, and cefaclor at less than or equal to 2 micrograms/ml, although many isolates of Enterobacter cloacae, Citrobacter freundii, and Serratia marcescens resistant to cefotaxime were not inhibited by these agents. A marked inoculum effect was noted for Enterobacteriaceae carrying the Richmond-Sykes type 1A chromosomally mediated beta-lactamases, but plasmid-mediated beta-lactamases did not hydrolyze the compounds. Both drugs inhibited the chromosomally mediated beta-lactamase of E. cloacae, P99.
PMCID: PMC180573  PMID: 3490827
24.  Molecular epidemiology of acquisition of ceftazidime-resistant gram-negative bacilli in a nonoutbreak setting. 
Journal of Clinical Microbiology  1997;35(10):2602-2605.
We prospectively studied the acquisition of ceftazidime-resistant gram-negative bacilli (CAZ-RGN) in two surgical intensive care units (SICU) during a nonoutbreak period. Surveillance cultures were obtained from patients at the time of admission and serially thereafter. CAZ-RGN isolates were typed by pulsed-field gel electrophoresis (PFGE). Three hundred and forty-three patients were enrolled from whom 1,621 baseline and follow-up cultures were obtained. The most common species isolated from patients were Pseudomonas aeruginosa (22), Enterobacter cloacae (21), Acinetobacter spp. (13), Enterobacter aerogenes (11), Citrobacter spp. (10), Pseudomonas spp. (non P. aeruginosa) (9), and Stenotrophomonas spp. (7). For each species, PFGE strain types were highly diverse; no single type was recovered from more than four patients. Twenty-eight patients acquired a CAZ-RGN during the SICU stay; in six (21%), emergence of resistance from a previously susceptible strain was documented on the basis of matching serial strain types. Transmission of CAZ-RGN between patients occurred but was infrequent, as judged by analyzing strain types of epidemiologically linked patients. In conclusion, colonization with CAZ-RGN in SICU was associated with diverse species and strains, as determined by molecular typing. Emergence of resistance from previously susceptible strains appeared to be more important than horizontal transmission in acquisition of CAZ-RGN in a nonoutbreak period.
PMCID: PMC230018  PMID: 9316915
25.  βlasEN: Microdilution Panel for Identifying β-Lactamases Present in Isolates of Enterobacteriaceae 
Journal of Clinical Microbiology  2002;40(1):123-127.
A dried investigational use-only microdilution panel named βlasEN (a short named derived from the panel’s purpose, to identify β-lactamases in Enterobacteriaceae) containing 10 β-lactam drugs with and without β-lactamase inhibitors was developed to identify β-lactamases among clinical isolates of Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Citrobacter koseri, Citrobacter freundii group, Enterobacter spp., and Serratia marcescens. The MICs obtained with a collection of 383 organisms containing well-characterized β-lactamases were used to develop numeric codes and logic pathways for computerized analysis of results. The resultant logic pathways and βlasEN panel were then used to test and identify β-lactamases among 885 isolates of Enterobacteriaceae recovered in cultures obtained at six different hospital laboratories across the United States. β-Lactamases present in 801 (90.5%) of the 885 isolates were identified by βlasEN by using the existing logic pathways and codes or after minor modifications were made to the existing codes. The 84 strains that gave codes that βlasEN could not identify were collected, reidentified, and retested by using βlasEN. Three strains had been misidentified, 54 strains gave different codes upon repeat testing that could be identified by βlasEN, and 27 strains repeated new codes. The β-lactamases in these strains were identified, and the new codes were added to the βlasEN logic pathways. These results indicate that βlasEN can identify clinically important β-lactamases among most isolates of Enterobacteriaceae. The results also show that good quality control and attention to proper performance of the tests are essential to the correct performance of βlasEN.
PMCID: PMC120116  PMID: 11773104

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