Nonenteric Gram-negative Bacilli Research Articles

Investigation of Melioidosis Using Blood Culture and Indirect Hemagglutination Assay Serology among Patients with Fever, Northern Tanzania.

.Prediction models indicate that melioidosis may be common in parts of East Africa, but there are few empiric data. We evaluated the prevalence of melioidosis among patients presenting with fever to hospitals in Tanzania. Patients with fever were enrolled at two referral hospitals in Moshi, Tanzania, during 2007–2008, 2012–2014, and 2016–2019. Blood was collected from participants for aerobic culture. Bloodstream isolates were identified by conventional biochemical methods. Non–glucose-fermenting Gram-negative bacilli were further tested using a Burkholderia pseudomallei latex agglutination assay. Also, we performed B. pseudomallei indirect hemagglutination assay (IHA) serology on serum samples from participants enrolled from 2012 to 2014 and considered at high epidemiologic risk of melioidosis on the basis of admission within 30 days of rainfall. We defined confirmed melioidosis as isolation of B. pseudomallei from blood culture, probable melioidosis as a ≥ 4-fold rise in antibody titers between acute and convalescent sera, and seropositivity as a single antibody titer ≥ 40. We enrolled 3,716 participants and isolated non-enteric Gram-negative bacilli in five (2.5%) of 200 with bacteremia. As none of these five isolates was B. pseudomallei, there were no confirmed melioidosis cases. Of 323 participants tested by IHA, 142 (44.0%) were male, and the median (range) age was 27 (0–70) years. We identified two (0.6%) cases of probable melioidosis, and 57 (17.7%) were seropositive. The absence of confirmed melioidosis from 9 years of fever surveillance indicates melioidosis was not a major cause of illness.

UNUSUAL PATH FOR DISCOVERY OF SEPSIS ETIOLOGY

SESSION TITLE: Wednesday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/23/2019 09:45 AM - 10:45 AM INTRODUCTION: Sepsis-3 defines sepsis as a life-threatening organ dysfunction caused by dysregulated host response to infection. The most challenging patients are the ones who have no clear source of infection. Current guidelines recommend empiric coverage for aerobic gram-positive and aerobic enteric gram-negative bacteria. When broad spectrum antibiotics fail, review of antibacterial spectra of activity and assistance of differential diagnosis generators may pave the path for culprit discovery. We present a case where the differential diagnosis generator helped us accurately diagnose and guide the appropriate therapy. CASE PRESENTATION: A female of 70-years with a history of osteoarthritis presented with four weeks of fever, weight loss, night sweats, and fatigue. She was hypotensive, febrile, tachycardic and tachypneic. Sepsis protocol was activated. Laboratory data revealed WBC 2.7 K/UL, Hgb 9.8 g/dL, PLT 77 K/DL, AST 71 IU/L ALT 49 IU/L, CRP 12 mg/dL, ESR 41 mm/hr. Ferritin 7138 ng/mL, LDH 570 IU/L. She failed to improve for the first 48 hours despite IV Vancomycin and Cefepime. A contrast-enhanced CT scan of the abdomen revealed splenic hypodensities; laboratory workup for Q-fever, RMSF, salmonella, and Lyme’s disease was sent to evaluate for secondary hemophagocytic lymphohistiocytosis (HLH). A liver biopsy was also obtained. Lack of clinical and laboratory improvement prompted us to review our empiric coverage. The clinical picture was thought to be secondary to an infection, therefore, we had narrowed our antibiotics to only doxycycline for non-enteric gram-negative bacilli. We also utilized Isabel Healthcare Differential Diagnosis (DDX) Tool, which generated ten differential diagnosis including Brucellosis. Our patient later admitted to consuming homemade cheese on her last visit to Mexico. Brucella serology and blood cultures were obtained. Fever resolved 48 hours after doxycycline was initiated. Later, blood cultures grew Brucella spp. Currently, our patient remains symptom-free and all laboratory abnormalities have normalized. DISCUSSION: Sepsis guidelines recommend empiric coverage for common pathogens with no clear advice on uncommon infectious agents. A detailed travel and social history are crucial, especially in patients who do not improve on empiric broad spectrum antibiotics. In addition, medical decision making relies on pattern recognition of illness scripts accumulated over time. Historically, we refer to textbooks for the DDX of each symptom. Nowadays, we have more sophisticated DDX generators that incorporate epidemiological data, clinical and laboratory findings to create a DDX list. In a study, the pooled accurate diagnosis retrieval rate for DDX tools was as high as 0.70. CONCLUSIONS: It is imperative to identify significant and clinically relevant data. DDX generators may be useful resources for clinicians and it may also increase the medical knowledge. Reference #1: PMID: 26157077 DISCLOSURES: No relevant relationships by Jose Zabala-Genovez, source=Web Response

Clinical Features and Outcomes of Spontaneous Bacterial Peritonitis Caused by Non-enteric Gram-Negative Bacilli: A Matched Case-Control Study

Clinical Features and Outcomes of Spontaneous Bacterial Peritonitis Caused by Non-enteric Gram-Negative Bacilli: A Matched Case-Control Study

Antimicrobial activity of prulifloxacin tested against a worldwide collection of gastroenteritis-producing pathogens, including those causing traveler's diarrhea.

Prulifloxacin, the prodrug of ulifloxacin (active component), is a newer fluoroquinolone with broad activity against enteric and nonenteric gram-negative bacilli. Ulifloxacin and other oral comparator agents were tested for activity against 582 gastroenteritis strains from global surveillance studies. Ulifloxacin was highly active against Escherichia coli, Salmonella spp., Shigella spp., Yersinia spp., Vibrio spp., Aeromonas spp., and Plesiomonas spp. (MIC(50)s and MIC(90)s, <or=0.03 microg/ml and <or=0.06 microg/ml, respectively). Only rare Aeromonas spp., Campylobacter spp., and E. coli displayed elevated MIC results (>or=4 microg/ml). Ciprofloxacin exhibited similar activity but was two- to fourfold less potent. Presently approved for clinical use in certain European countries and Japan, ulifloxacin was the most active of the antimicrobial agents tested against these gastroenteritis-causing pathogens.

Global resistance trends and the potential impact on empirical therapy

Globally, antibiotic resistance continues to be an increasing problem. The emergence of methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), and extended spectrum β-lactamase-producing Enterobacteriaceae has seriously reduced the number of empirical agents suitable for selected indications. Increasing Gram-negative resistance has also negatively impacted the physician's alternatives when choosing adequate initial therapy; increased reliance on the carbapenem class as empirical agents has led to the emergence of multidrug resistance in non-enteric Gram-negative bacilli. There is a critical need for new, broad-spectrum alternatives to the currently available broad-spectrum agents.

Evaluation of the Phoenix 100 ID/AST System and NID Panel for Identification of Enterobacteriaceae , Vibrionaceae , and Commonly Isolated Nonenteric Gram-Negative Bacilli

The Phoenix 100 ID/AST system (Becton Dickinson Co., Sparks, Md.) is an automated system for the identification and antimicrobial susceptibility testing of bacterial isolates. This system with its negative identification (NID) panel was evaluated for its accuracy in the identification of 507 isolates of the family Enterobacteriaceae, 57 other nonenteric gram-negative isolates that are commonly isolated in clinical microbiology laboratories, and 138 isolates of the family Vibrionaceae. All of the isolates had been characterized by using approximately 48 conventional tube biochemicals. Of the 507 isolates of the Enterobacteriaceae, 456 (89.9%) were correctly identified to the genus and species levels. The five isolates of Proteus penneri required an off-line indole test, as suggested by the system to differentiate them from Proteus vulgaris. The identifications of 20 (3.9%) isolates were correct to the genus level but incorrect at the species level. Two (0.4%) isolates were reported as "no identification." Misidentifications to the genus and species levels occurred for 29 (5.7%) isolates of the Enterobacteriaceae. These incorrect identifications were spread over 14 different genera. The most common error was the misidentification of Salmonella species. The shortest time for a correct identification was 2 h 8 min. The longest time was 12 h 27 min, for the identification of a Serratia marcescens isolate. Of the 57 isolates of nonenteric gram-negative bacilli (Acinetobacter, Aeromonas, Burkholderia, Plesiomonas, Pseudomonas, and Stenotrophomonas spp.), 48 (84.2%) were correctly identified to the genus and species levels and 7 (12.3%) were correctly identified to the genus level but not to the species level. The average time for a correct identification was 5 h 11 min. Of the Vibrionaceae spp., 123 (89.1%) were correctly identified at the end of the initial incubation period, which averaged 4 h. Based on the findings of this study, the Phoenix 100 ID/AST system NID panel falls short of being an acceptable new method for the identification of the Enterobacteriaceae, Vibrionaceae, and gram-negative nonenteric isolates that are commonly encountered in many hospital microbiology laboratories.

Antimicrobial susceptibility of uncommonly isolated non-enteric Gram-negative bacilli

The frequency of occurrence and antimicrobial susceptibility patterns of 3059 non-enteric Gram-negative bacilli (NGB), other than Pseudomonas aeruginosa and Acinetobacter spp., consecutively collected as part of the SENTRY Antimicrobial Surveillance Program (1997–2003) were reviewed. During this period, a total of 221,084 bacterial isolates were collected from several clinical specimens worldwide, including 25,305 (11.5%) NGB. Acinetobacter spp. and P. aeruginosa accounted for 82.7% of the NGB isolates and have been excluded from this analysis. The antimicrobial susceptibility results of 3509 strains from 13 species/genera have been analysed in this review. The isolates were tested by reference broth microdilution methods in three central laboratories using common reagents and procedures. More than 30 antimicrobial agents were tested and the results for the 18 most active compounds are reported here. Stenotrophomonas maltophilia (2076 strains; 59.2%) was the most frequently isolated pathogen in this group, followed by Aeromonas spp. (385 strain; 11.0%), Burkholderia cepacia (269 strains; 7.7%), Pseudomonas fluorescens/ putida (253 strains; 7.2%) and Alcaligenes spp. (236 strains; 6.7%). All other species/genera accounted for less than 3% of the isolates analysed. The antimicrobial agents with the most consistent activity against the NGB evaluated in the present study were the newer fluoroquinolones gatifloxacin and levofloxacin with 84.1 and 84.9% susceptibility overall. Trimethoprim/sulphamethoxazole was active against 85.3% of the isolates tested, but showed reduced activity against P. fluorescens/putida (22.1% susceptibility). Antimicrobial susceptibility varied significantly between species/genera and the geographical regions evaluated. Thus, proper identification and quantitative susceptibility testing will be required for the treatment of NGB infections. Extensive worldwide surveillance programmes remain extremely important to guide empirical antimicrobial therapy for rarely isolated pathogens and also for pathogens that are not routinely tested due to the lack of standardised susceptibility testing methods.

A7.12 The efficacy and safety of tigecycline in the treatment of complicated intra-abdominal infections: Results of pooled clinical trial data

Cefditoren, a broad-spectrum orally administered cephalosporin ester, has documented in vitro efficacy against many Gram-positive and -negative pathogens and stability against clinically important β-lactamases. We have reviewed the microbiology and the pharmacokinetic/pharmacodynamic literature regarding the spectrum and potency of this newer agent against the major etiologic agents of community-acquired respiratory infection, (Streptococcus pneumoniae, Hemophilus influenzae and Moraxella catarrhalis), as well as the Enterobacteriaceae and non-enteric Gram-negative bacilli, staphylococci, and other anerobic and anaerobic Gram-positive cocci. The level of cefditoren activity against S. pneumoniae (MIC90, 0.5 μg/mL) was superior to all marketed oral cephalosporins and at least equal to amoxicillin ± clavulanate. H. influenzae (MIC90, 0.016–0.03 μg/mL) and M. catarrhalis (MIC90, 0.06–0.5 μg/mL) were also very susceptible to cefditoren. In contrast to cefixime and ceftibuten, cefditoren was active against oxacillin-susceptible staphylococci (MIC90, ≤ 1 μg/mL) at a level comparable to cefuroxime axetil, cefaclor or cefprozil. Enterococci, Pseudomonas aeruginosa and most anaerobes (Gram-negative) were not cefditoren-susceptible, but most Enterobacteriaceae, β-haemolytic and viridans group streptococci were highly susceptible. Furthermore, an overview of key in vitro susceptibility testing methods and issues including disk diffusion testing and Etest (AB BIODISK, Solna, Sweden) method accuracy, interpretive criteria, and pharmacodynamic considerations for the selection of a breakpoint concentration are provided. The rapid bactericidal nature of the antibacterial activity of cefditoren, its post antibiotic effect, penicillin binding protein targets, and extent of β-lactamase stability are all favorable qualities. In conclusion, this orally administered (BID) β-lactam possesses promise for use against commonly isolated problematic respiratory tract pathogens such as penicillin-non-susceptible pneumococci and β-lactamase-positive M. catarrhalis or H. influenzae. Success in the clinical trials will further define the role of cefditoren in this era of emerging resistant bacterial pathogens.

Cefditoren in vitro activity and spectrum: a review of international studies using reference methods

Cefditoren, a broad-spectrum orally administered cephalosporin ester, has documented in vitro efficacy against many Gram-positive and -negative pathogens and stability against clinically important β-lactamases. We have reviewed the microbiology and the pharmacokinetic/pharmacodynamic literature regarding the spectrum and potency of this newer agent against the major etiologic agents of community-acquired respiratory infection, ( Streptococcus pneumoniae, Hemophilus influenzae and Moraxella catarrhalis), as well as the Enterobacteriaceae and non-enteric Gram-negative bacilli, staphylococci, and other anerobic and anaerobic Gram-positive cocci. The level of cefditoren activity against S. pneumoniae (MIC 90, 0.5 μg/mL) was superior to all marketed oral cephalosporins and at least equal to amoxicillin ± clavulanate. H. influenzae (MIC 90, 0.016–0.03 μg/mL) and M. catarrhalis (MIC 90, 0.06–0.5 μg/mL) were also very susceptible to cefditoren. In contrast to cefixime and ceftibuten, cefditoren was active against oxacillin-susceptible staphylococci (MIC 90, ≤ 1 μg/mL) at a level comparable to cefuroxime axetil, cefaclor or cefprozil. Enterococci, Pseudomonas aeruginosa and most anaerobes (Gram-negative) were not cefditoren-susceptible, but most Enterobacteriaceae, β-haemolytic and viridans group streptococci were highly susceptible. Furthermore, an overview of key in vitro susceptibility testing methods and issues including disk diffusion testing and Etest (AB BIODISK, Solna, Sweden) method accuracy, interpretive criteria, and pharmacodynamic considerations for the selection of a breakpoint concentration are provided. The rapid bactericidal nature of the antibacterial activity of cefditoren, its post antibiotic effect, penicillin binding protein targets, and extent of β-lactamase stability are all favorable qualities. In conclusion, this orally administered (BID) β-lactam possesses promise for use against commonly isolated problematic respiratory tract pathogens such as penicillin-non-susceptible pneumococci and β-lactamase-positive M. catarrhalis or H. influenzae. Success in the clinical trials will further define the role of cefditoren in this era of emerging resistant bacterial pathogens.

In vitro evaluation of cefepime and other broad-spectrum β-lactams in Taiwan medical centers

The rates of resistance to commonly used antimicrobial agents have been documented to be at alarmingly high levels in Taiwan for both Gram-positive and Gram-negative species. This study was conducted to assess the current resistance patterns in six medical centers strictly controlled using a common MIC methodology and quality assurance measures. Cefepime, a new clinically introduced broad-spectrum “fourth-generation” cephalosporin, was compared to other members in this class including ceftazidime, cefpirome, ceftriaxone, piperacillin/tazobactam, and imipenem. These antimicrobials were tested against ten species groups of common clinical isolates of Enterobacteriaceae, non-enteric Gram-negative bacilli, and oxacillin-susceptible Staphylococcus spp. The results confirmed that extended spectrum β-lactamase (ESBL) production in Klebsiella spp. (21.7%) and Escherichia coli (16.7%) was common in all medical centers surveyed. Cefepime was more active against these two species as well as against Amp C producing species, indole-positive Proteae, and Acinetobacter species. The activity of cefepime was comparable although slightly less than that of ceftazidime against Serratia spp. and Pseudomonas aeruginosa strains. All or nearly all staphylococci isolates were susceptible to the β-lactam antimicrobial agents, except for ceftazidime. Overall, these antimicrobial agents had descending spectrums of activity as follows: imipenem > cefepime > cefpirome > piperacillin/tazobactam > ceftazidime > ceftriaxone for the 550 isolates tested. Cefepime seems to be an important broad-spectrum β-lactam that can be used with confidence against many important pathogens in Taiwan, including those harboring resistance mechanisms. A continued surveillance program seems prudent for this geographic area.

Evaluation of the in vitro antimicrobial activity of cefepime compared to other broad-spectrum β-lactams tested against recent clinical isolates from 10 Chinese hospitals

A surveillance study was initiated in China in 1998 in which 10 medical centers participated. The susceptibility profiles of 996 commonly occurring pathogens belonging to 10 different species groups were tested by the Etest (AB BIODISK, Solna, Sweden) against six broad-spectrum β-lactam antimicrobial agents (cefepime, ceftazidime, ceftriaxone, imipenem, cefopera-zone/sulbactam and piperacillin or oxacillin). Quality control was closely monitored and cefepime- and/or imipenem -resistant Enterobacteriaceae were referred to the reference laboratory (University of Iowa College of Medicine, Iowa City, IA) for confirmation. The isolates of Citrobacter spp. and Enterobacter spp. were generally inhibited by imipenem (100% susceptible) and cefepime (89–94%), but were more resistant to the other drugs tested (≤74% susceptible). The indole-positive Proteus spp. and Serratia spp. isolates were >94% susceptible to all tested β-lactams except piperacillin. Organisms capable of producing extended spectrum β-lactamases (ESBLs), which included Klebsiella spp. and Escherichia coli, were most susceptible to imipenem (100%) and cefepime (>90%). Among the non-enteric Gram-negative bacilli, all drugs were marginally active against Pseudomonas aeruginosa (MIC 90s, 32- >256 ug/mL) and the Acinetobacter spp. were rather resistant to all the compounds, except imipenem (96% susceptible). All strains of Staphylococcus spp. were susceptible to the tested antimicrobials except for ceftazidime, which had a low potency (MIC 90, 12–16 μg/mL) against Chinese isolates with MICs that fell into the intermediate category. Cefepime, the fourth-generation cephalosporin, showed a very broad spectrum of activity against Gram-negative pathogens as well as oxacillin-susceptible Staphylococcus spp. that was comparable with imipenem (widest spectrum) and superior to the other tested β-lactams overall. Continued monitoring of clinical strains in China seems necessary to guide chemotherapy.

Antimicrobial Activity and Spectrum Investigation of Eight Broad-Spectrum β-Lactam Drugs: A 1997 Surveillance Trial in 102 Medical Centers in the United States

Because antimicrobial agents become less effective after the emergence of resistance mechanisms in clinically prevalent pathogens, physicians must utilize local, regional, and national antimicrobial susceptibility surveillance data to assist in choices of appropriate agents. An investigation of the spectrum and potency of eight broad-spectrum β-lactam drugs (cefepime, cefotaxime, ceftazidime, ceftriaxone, imipenem, piperacillin with or without tazobactam, and ticarcillin/clavulanic acid) was performed using a common protocol and method (Etest; AB BIODISK, Solna, Sweden) in 102 clinical microbiology laboratories in the United States. A total of 9777 strains of Gram-negative bacilli were tested from late 1996 through April 1997. Quality assurance measures using three control strains observed quality control failures in 13 laboratories (usually ticarcillin/clavulanic acid or piperacillin), but only 2% of results required deletion. A total of 33.4% of Enterobacter spp. (1977 strains) were either resistant or intermediately susceptible to ceftazidime. Only imipenem (99.6% susceptible) and cefepime (99.1%) remained highly active against strains of Enterobacter, as well as Citrobacter freundii, indole-positive Proteae, and Serratia spp. Ceftazidime-resistant Escherichia coli and Klebsiella pneumoniae were detected at rates of 10.3% and 23.8%, respectively. Although these were participant-selected strains, only imipenem and cefepime had broad-spectrum coverage (≥97.1%) against these extended-spectrum β-lactamase phenotypes. A dominant number of these extended-spectrum β-lactamase phenotypes were reported from medical centers in the Northeast, but a nationwide distribution was observed. Among the nonenteric Gram-negative bacilli (4057 strains), the rank order of susceptibility (percent inhibited at published breakpoint concentrations) was: imipenem (86.1%) > piperacillin/tazobactam (80.1%) > cefepime (77.1%) > ceftazidime = piperacillin (74.9%) > ticarcillin/clavulanic acid (61.6%) > cefotaxime (18.2%) > ceftriaxone (12.9%). The cephalosporins, cefepime and ceftazidime, had rates of resistance for the 3005 Pseudomonas aeruginosa isolates of 10.1% and 14.4%, respectively. For all Gram-negative strains tested, only two contemporary β-lactam antimicrobials exhibited >90% inhibition of strains, imipenem at 93.6% and cefepime at 90.2%. These drugs were superior to the other tested compounds (48.8–84.3%). Ticarcillin/clavulanic acid had the narrowest spectrum of activity (48.8% of isolates susceptible). These results indicate that carbapenems and a new fourth-generation cephalosporin, cefepime, possess usable in vitro potencies against current clinical strains of Gram-negative bacilli, many of which harbored resistance to other antimicrobial agents.

Antimicrobial activity of 12 broad-spectrum agents tested against 270 nosocomial blood stream infection isolates caused by non-Enteric Gram-negative bacilli: Occurrence of resistance, molecular epidemiology, and screening for metallo-enzymes

A total of 270 recent nosocomial blood stream isolates of non-Enterobacteriaceae Gram-negative bacilli representing nearly 50 U.S. medical centers were characterized. The numbers of isolates of individual organisms were: Pseudomonas aeruginosa ( n = 204), Acinetobacter spp. ( n = 48), and Stenotrophomonas maltophilia ( n = 18). MICs were determined using the broth microdilution susceptibility method with 12 antimicrobial agents: piperacillin, piperacillin/tazobactam, ceftriaxone, ceftazidime, cefepime, imipenem, ciprofloxacin, ofloxacin, amikacin, gentamicin, tobramycin, and trimethoprim/sulfamethoxazole. Based on current National Committee for Clinical Laboratory Standards breakpoints, rates of resistance to cefepime, ceftazidime, and imipenem were as follows: P. aeruginosa, 3, 9, and 5%; Acinetobacter spp., 2, 37, and 0%; and S. maltophilia, 88.7, 35.3, and 100%, respectively. Trimethoprim/sulfamethoxazole was the most active agent against S. maltophilia (100% susceptible). Twenty-eight isolates of P. aeruginosa that expressed high levels of resistance to ceftazidime (MIC, >256 μg/mL) and imipenem (MIC, >32 μg/mL) were examined for potential metallo-β-lactamase production by polymerase chain reaction and were found to be negative. Molecular typing of P. aeruginosa isolates revealed many patient-unique strains, but also noted clustering of infections due to isolates of the same DNA type, suggesting possible nosocomial transmission in 9 of 14 medical centers. Given the resistance profile and pathogenic potential of these non-enteric Gram-negative bacilli, considerable effort should be exerted to develop and enforce infection control and antimicrobial utilization practices that will limit the spread of these organisms in the hospital environment.

Comparative antimicrobial activity of piperacillin-tazobactam tested against more than 5000 recent clinical isolates from five medical centers a reevaluation after five years

Piperacillin combined with tazobactam at a fixed concentration (4 μg/ml) and a ratio (8:1) was tested against 5029 aerobic isolates and 447 fastidious organisms, including anaerobes. Among the Enterobacteriaceae, >95% inhibition was shared only by imipenem (99.1% at ⩽4 μg/ml), and some newer cephalosporins (95.1%–99.8% at ⩽8 μg/ml), and piperacillin-tazobactam ( 95.8% at ⩽ 16 4 μg/ml ). Piperacillin-tazobactam was the most active agent tested against nonenteric Gramnegative bacilli (93.5% at ⩽8 μg/ml). Ampicillin-sulbactam was the most active agent against staphylococci (95.0% at ⩽8 μg/ml), followed by imipenem (91.8%), piperacillin-tazobactam ( 89.3% at ⩽ 8 4 μg/ml ), and cefepime (86.2% at ⩽8 μg/ml). Against the enterococci, only ampicillin (93.0% at ⩽8 μg/ml) with or without sulbactam, piperacillin (91.0% at ⩽16 μg/ml) with or without tazobactam, and imipenem (91.0%) had acceptable activity. Piperacillin-tazobactam and imipenem were the most active drugs tested against all aerobic isolates, inhibiting 93.5% of isolates each. Piperacillin-tazobactam inhibited all fastidious isolates tested, including Haemophilus influenzae ( MIC 90, 0.094 4 μg/ml ), Moraxella catarrhalis ( MIC 90, 0.064 4 μg/ml ), Neisseira gonorrhoeae ( MIC 90, ⩽ 0.016 4 μg/ml ), and Streptococcus pneumoniae ( all MICs, ⩽ 4 4 μg/ml ). Against the anaerobic isolates, the most broad-spectrum antimicrobial agents tested were imipenem (100.0%), piperacillin-tazobactam ( 99.5% at ⩽ 32 4 μg/ml ), metronidazole (98.4% at ⩽8 μg/ml), and ticarcillin-clavulanic acid ( 95.1% at ⩽ 32 2 μg/ml ). These results are nearly identical to a previous study involving the same five medical centers in 1989. Piperacillin-tazobactam appears to remain a highly effective β-lactamase inhibitor combination with a wide empiric spectrum and potency in teaching hospitals.

LevofloxacinIn VitroActivity: Results from an International Comparative Study with Ofloxacin and Ciprofloxacin

Levofloxacin, the S-(-)-isomer of ofloxacin, was compared to ofloxacin and ciprofloxacin against > 6000 recent clinical isolates of Gram-positive and Gram-negative bacteria from six different countries. This international multicenter study demonstrated a high level of antibacterial activity of levofloxacin against all the members of Enterobacteriaceae [minimum inhibitory concentration (MIC)50s, < or = 0.03 to 0.12 mg/L] except Providencia rettgeri (MIC50, 2 mg/L), and Providencia stuartii (MIC50, 1 mg/L). Oxacillin-susceptible staphylococci (MIC50s, 0.12 to 0.25 mg/L), enterococci (MIC50s, 0.5 to 2 mg/L), and streptococci (MIC50s, 0.5 mg/L) were also susceptible to levofloxacin, but most isolates of oxacillin-resistant staphylococci had MICs of > or = 4 mg/L. Levofloxacin was also active against non-enteric Gram-negative bacilli, including Acinetobacter species (MIC50s, < or = 0.03 to 1 mg/L), Pseudomonas species (MIC50s, 0.5 to 1 mg/L) and Xanthomonas maltophilia (MIC50, 0.5 mg/L). Overall, levofloxacin inhibited 50% and 90% of all the tested strains at the concentrations of 0.12 and 4 mg/L, respectively. The activity of levofloxacin was generally two-fold greater than ofloxacin and equal to or slightly less potent than ciprofloxacin.

Antimicrobial activity of FK-037, a new broad-spectrum cephalosporin international in vitro comparison with cefepime and ceftazidime

The in vitro activity of FK-037, a new parenteral 7-aminothiazolyl-methoxyimino cephalosporin, was compared with cefepime and ceftazidime against 6094 aerobic isolates collected in six medical centers worldwide. FK-037 demonstrated potent activity against the Enterobacteriaceae family except for some Enterobacter spp., Providencia spp., and Serratia liquefaciens (MIC 90s, ⩾16 μg/ml). Against nonenteric Gram-negative bacilli, all compounds tested showed similar, but more limited activity. The FK-037 MIC 50s for Pseudomonas spp. and P. aeruginosa were 2 and 4 μg/ml, respectively. The least susceptible organisms were Xanthomonas maltophilia, enterococci, and Bacillus spp. (MIC 50s, >16 μg/ml), followed by Flavobacterium spp., other nonenterics, and oxacillin-resistant Staphylococcus aureus (MIC 50s, 16 μg/ml). Good FK-037 activity was observed against oxacillin-susceptible staphylococci as well as against β-hemolytic and viridans-group streptococci (MIC 90 range, ⩽0.12 to 2 μg/ml). While FK-037 was slightly more active than cefepime against Gram-positive organisms, enteric bacilli were most susceptible to cefepime. Overall, the antibacterial spectrum of both FK-037 and cefepime was superior to ceftazidime.

Antimicrobial activity of a new antipseudomonal dual-action drug, Ro 25-0534

Ro 25-0534, a tertiary amine-linked dual action combination (DAC) of a catechol cephalosporin and ciprofloxacin, was compared with a previously described DAC (Ro 23-9424), ciprofloxacin and cefotaxime. A total of 688 recent clinical isolates were tested and an additional collection of 110 Gram-negative bacilli possesing documented resistance to broad-spectrum antimicrobials were used. Ro 25-0534 was active against all tested species of Enterobacteriaceae (MIC 90 range, 0.06–2 μg/ml), oxacillin-susceptible staphylococci, β-hemolytic streptococci, and penicillin-susceptible pneumococci (MIC 90 range, 1–2 μg/ml), Haemophilus influenzae (MIC 90 range, 0.25–0.5 μg/ml), Moraxella catarrhalis (MIC 90, 0.5 μg/ml), and most nonenteric Gram-negative bacilli (MIC 90 range, 2–4 μg/ml) such as Pseudomonas aeruginosa, Acinetobacter spp., and Xanthomonas maltophilia. Enterococci and Bacteroides fragilis isolates were resistant to Ro 25-0534. The Ro 25-0354 potency against most susceptible strains was generally severalfold less than that of Ro 23-9424 (except for Pseudomonas-Xanthomonas) or ciprofloxacin alone.

In VittoComparison Activity ofOPC-17116, a New Fluoroquinolone, Against More Than 5,000 Recent Clinical Isolates from Five Medical Centers

The in vitro activity of OPC-17116, a new fluoroquinolone, was compared with those of ciprofloxacin, ofloxacin and cefixime. A total of 5,231 fresh clinical isolates from five geographically separate US medical centers were tested. The primary results of this study are: 1. OPC-17116 is very active against Enterobacteriaceae [MIC90s, 0.015-1 microgram/ml, except Providencia rettgeri (MIC90, > 8 micrograms/ml)], 2. among nonenteric Gram-negative bacilli (e.g. Xanthomonas maltophilia, MIC90, 2 micrograms/ml) and Gram-positive cocci (e.g. oxacillin-susceptible staphylococci, MIC90s, 0.12-0.5 microgram/ml) OPC-17116 demonstrated higher activity than ciprofloxacin or ofloxacin, 3. the quinolones were more active than cefixime against most of the species tested, especially against Gram-positive and non-enteric Gram-negative organisms. The results of this study, associated with prior documented favorable qualities, support continued investigation of OPC-17116 for clinical use.

In vitro antimicrobial activity of CP-99433 compared with other fluoroquinolones

CP-99433 is a new C-7 diazabicyclofluoroquinolone with a broad spectrum of activity that includes Enterobacteriaceae, Gram-positive cocci, and nonenteric Gram-negative bacilli. Potent activity was demonstrated against Pseudomonas aeruginosa [minimum inhibitory concentration (MIC 90, 0.5 μg/ml), Xanthomonas maltophilia (MIC 90, 1 μg/ml), and all Streptococcus species (MIC 90s, 0.25–1 μg/ml). Only CP-99433 was active against Enterococcus faecium (MIC 50, 2 μg/ml). CP-99433 also demonstrated activity against several ciprofloxacin-resistant staphylococci. Additional studies of CP-99433 activity appear indicated.

Collaborative evaluation of the Radiometer Sensititre AP80 for identification of gram-negative bacilli.

A multicenter trial of the Sensititre AP80 panel read on the Sensititre AutoReader (Radiometer America, Westlake, Ohio) for the automated identification of gram-negative bacilli was conducted with 1,023 clinical isolates (879 members of the family Enterobacteriaceae plus 144 nonenteric organisms). Assignment of taxa was based on the computer-assisted interpretation of the results of a series of reactions with fluorogenic enzyme substrates after 5 h of incubation, with an incubation interval of approximately 18 h used when indicated. Accuracy was determined initially by comparison with the results obtained with the API 20E or Rapid NFT system (Analytab Products, Plainview, N.Y.). Isolates showing discrepancies were identified by using conventional biochemical profiles. Identifications were available after 5 h of incubation for 918 isolates (90%). Agreements with reference results for members of the family Enterobacteriaceae were 95.3 and 92.5% at the genus and species levels, respectively, and for the nonmembers of the family Enterobacteriaceae, the agreements with reference results were 95.1 and 84.7%, respectively. The Sensititre AP80 panel was found to be simple and convenient to use, allowed for the testing of three isolates per panel, required minimal supplementary testing for completion of identification, performed in a reproducible fashion, and demonstrated an accuracy of same-day identification comparable to that reported for other automated systems. The AP80 panel appears well suited for routine use in the clinical microbiology laboratory as an automated means of identifying both members of the family Enterobacteriaceae and nonenteric gram-negative bacilli.