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Objectives: To study multicenter antibiotic practices for suspected early-onset sepsis (EOS) with negative blood cultures (NegBCs) and to identify opportunities for reduction of antimicrobial exposure., Design: Retrospective study., Setting: Thirty academic hospitals (University HealthSystem Consortium) located in 24 states., Methods: Data were from a survey of 790 extremely low birth weight (ELBW) infants. Total antibiotic exposures (antibiotic-days per patient) were calculated., Results: On admission to the NICU, 94% of 790 ELBW infants had BCs performed and empiric antibiotics initiated. When PosBC and NegBC infants were compared, 47 patients with PosBCs were similar to 695 with NegBCs in birth weight, gestational age (GA), and mortality. Patients with suspected EOS but NegBCs given ampicillin/aminoglycosides were grouped by length of administration and GA. For GA of 26 weeks or younger, 170 infants given a short (< or = 3 days) and 157 given a long (> or = 7 days) course were similar regarding birth weight, mortality, antepartum history, and CRIB scores, but were different (P < .01) in number receiving a third antimicrobial (3% and 17%) and antibiotic-days (23 and 38). For GA of 27 weeks or older, 113 infants given a short and 77 given a long course differed (P < .01) in number receiving a third antimicrobial (2% and 23%) and antibiotic-days (19 and 30)., Conclusions: Most suspected EOS infants with NegBCs are given antibiotics, but no antepartum historical risk factors or neonatal clinical signs explained prolonged administration. Discontinuing empiric antibiotics when BCs are negative in asymptomatic ELBW infants can reduce antimicrobial exposure without compromising clinical outcome.

Background: Gram-negative bacillary (GNB) airway colonization in mechanically ventilated newborns is associated with morbidity and mortality, which may be reduced if systemic antimicrobial therapy eradicates GNB from the airway. Efforts to do so in adults have met with variable success; similar experiences in newborns have not been reported., Methods: From 1991 through 1998, 531 very low-birth-weight infants were mechanically ventilated longer than 2 weeks. The study group was 106 infants with GNB airway colonization. Sixty-four other neonates in whom GNB nosocomial bloodstream infections developed served as antibiotic treatment outcome control., Results: Isolated from the airway were enteric (70 cases) and environmental (36 cases) GNB. Gentamicin alone or with ceftazidime (79), ceftazidime (11), piperacillin in combination with tazobactam or tobramycin (8), and tobramycin, in combination with ampicillin/sulbactam or mezlocillin (8) were the antimicrobials selected. Systemic antibiotics failed to eradicate GNB colonization in 97% of the cases. Six of the 106 infants with airway colonization died for reasons unrelated to infection. Sixty-four infants experienced 67 bloodstream infections as a result of enteric (53) and environmental (14) GNB. Gentamicin alone (23), with ceftazidime (26), or with clindamycin or ampicillin/sulbactam (9), piperacillin with tazobactam or tobramycin (3) and ceftazidime alone (6) were the antimicrobials selected. Survival occurred in 84% of the 67 nosocomial bloodstream infections., Conclusions: Systemic antibiotics do not consistently eradicate GNB from the airway of mechanically ventilated newborns, therefore its empirical use for prophylaxis or treatment of airway colonization should be discouraged.

Objective: To assess the prevalence of gram-positive coccal (GPC), gram-negative bacillary (GNB), and fungal blood-stream infections (BSIs) during a 12-year period in which a consistent antibiotic treatment protocol was in place; to evaluate the efficacy of these antibiotic policies in relation to treatment, to the emergence of bacterial or fungal resistance, and to the occurrence of infection outbreaks or epidemics., Study Design: Case series., Methods: Demographic, clinical, and bacteriological information from 363 infants born during 1986 through 1991 and 1992 through 1997 who developed 433 blood-culture-proven BSIs was analyzed. Early-onset BSIs were defined as those infections discovered within 48 hours of birth, and late-onset BSIs as those that occurred thereafter. Suspected early-onset BSIs were treated with ampicillin and gentamicin, and suspected late-onset BSIs with vancomycin and gentamicin. Antibiotics were changed on the basis of organism antimicrobial susceptibility., Results: Early-onset BSIs were noted in 52 of 21,336 live births and 40 of 20,402 live births during 1986 through 1991 and 1992 through 1997, respectively. GPC (83% due to group B streptococcus [GBS]) accounted for approximately one half of early-onset BSI cases and GNB (68% Enterobacteriaceae) for the remainder. Early-onset GBS declined from 24 to 11 cases (P=.04) and late-onset BSI increased from 111 to 230 cases (P<.01) from the first to the last study period. Sixty-eight percent of late-onset BSIs were due to GPC (primarily coagulase-negative Staphylococcus), 18% to GNB, and 14% to fungus. Over the study period, Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, and Pseudomonas aeruginosa isolated from the newborn intensivecare unit (unlike those strains from other hospital units) remained fully susceptible to ceftazidime and gentamicin. Although the hospitalwide prevalence of methicillin-resistant Staphylococcus aureus increased, all 17 newborn BSI cases were due to methicillin-sensitive strains. Prevalence of methicillin-resistant coagulase-negative Staphylococcus increased, although all strains remained vancomycin-susceptible, as did the 16 Enterococcus faecalis isolates. All fungi recovered (from 48 patients) were susceptible to amphotericin., Conclusion: We observed a decrease in the prevalence of early-onset BSIs due to GBS and an increase in late-onset BSIs due to GPC, GNB, and fungi. The combination of ampicillin and gentamicin for suspected early-onset BSIs and vancomycin and gentamicin for late-onset BSIs has been successful for treatment of individual patients without the occurrence of infection outbreaks or the emergence of resistance. Controlled antibiotic programs and periodic evaluations based on individual unit and not on hospitalwide antibiograms are advisable.

From 1991 to 1995, 8,975 nonfermentative gram-negative bacilli were isolated from patients at The Ohio State University Medical Center: 71% Pseudomonas aeruginosa, 14% Stenotrophomonas maltophilia, 7.6% Acinetobacter baumannii, and < 2% each of 25 other species. The MICs of trovafloxacin (CP-99,219), ciprofloxacin, ofloxacin, ampicillin-sulbactam, piperacillin, piperacillin-tazobactam, ceftazidime, cefoperazone, ceftriaxone, imipenem, tobramycin, and trimethoprim-sulfamethoxazole (TMP-SMZ) were determined for 308 isolates, representing 13 species, by a standardized broth microdilution method. The activities of all drugs were species dependent. The fluoroquinolones had inconsistent activity against most species, although several relatively uncommon nonfermenters were consistently susceptible or resistant. Trovafloxacin was considerably more active than ciprofloxacin and ofloxacin against S. maltophilia, A. baumannii, and several less common species. Among the beta-lactams, relative activities varied considerably; overall, imipenem had the broadest spectrum of activity but was inactive against S. maltophilia and Burkholderia cepacia isolates. Tobramycin and TMP-SMZ had stereotypic spectra of activity. Tobramycin was active against most species except S. maltophilia, Alcaligenes xylosoxidans subsp. xylosoxidans, Burkholderia spp., and Weeksella virosa. TMP-SMZ was active against most species except P. aeruginosa and Pseudomonas fluorescens-putida. A review of laboratory records indicated few changes in susceptibility patterns from 1991 to 1995; the only clear trend was toward increasing P. aeruginosa resistance to all classes of drugs.

Over 2800 clinical strains of the Bacteroides fragilis group were collected during a 5-year period from ten geographically separate sites and tested for their susceptibility to various antimicrobial agents using a broth microdilution method. Among the cephalosporins, ceftizoxime was the most active (13% resistance) and importantly exhibited relatively equal activity against both B. fragilis species and non-B. fragilis species. Cefotaxime exhibited similar activity with an overall resistance rate of 18%. Both ceftriaxone and cefoperazone were appreciably less active cephalosporins especially against non-B. fragilis species. With regard to cephamycins, cefoxitin (MIC90, 32 micrograms/ml) was more active than cefotetan (MIC90, > or = 256 micrograms/ml) and cefmetazole (MIC90, 64 micrograms/ml). Non-B. fragilis species were highly resistant to cefotetan and cefmetazole. Imipenem was highly active against all strains with the exception of four strains of B. fragilis. Ampicillin-sulbactam, amoxicillin-clavulanate, piperacillin-tazobactam, and cefoperazone-sulbactam were all highly active with resistance rates < 2%. No resistance was detected to metronidazole, whereas 14% of isolates were resistant to clindamycin. When compared with other studies, these findings underscore the wide variability in susceptibility patterns reported nationwide and the need to continue monitoring these patterns to aid in choosing the most active compounds for therapy.

For 45-60 days four geographically separate clinical laboratories tested routine clinical bacterial isolates for susceptibility to carumonam, aztreonam, BMY-28142, and ceftazidime by the broth microdilution method. All four drugs were highly active against Enterobacteriaceae, inhibiting greater than 96% of the 4887 strains tested at less than or equal to 8.0 microgram/ml. The minimal inhibitory concentration at which 50% of the isolates were inhibited for each drug was less than or equal to 0.125 micrograms/ml. Ceftazidime was the most active against nonenteric gram-negative bacilli (86% inhibited at less than or equal to 8.0 micrograms/ml), followed by BMY 28142 (82%), carumonam (75%), and aztreonam (68%). The two monobactams exhibited no activity against gram-positive cocci at the concentrations tested, whereas BMY-28142 had excellent activity against nonenterococcal streptococci and good activity against staphylococci.

The susceptibility of over 7000 recent clinical bacterial isolates to RO 23-6240, a new trifluorinated quinolone, was determined at four medical centers. Over 99% of Enterobacteriaceae and 97% of staphylococci were inhibited by less than or equal to 2.0 micrograms/ml of RO 23-6240. Only 71% of Pseudomonas spp. were inhibited by this concentration. Streptococci and enterococci were resistant to RO 23-6240. Clinical isolates of Haemophilus spp., pathogenic Neisseria spp., and Branhamella catarrhalis were inhibited by less than or equal to 0.25 micrograms/ml of RO 23-6240. This drug's antibacterial activity was comparable with that of enoxacin and norfloxacin, but was less than that of ciprofloxacin against most species. Using less than or equal to 2.0 micrograms/ml and greater than or equal to 8.0 micrograms/ml as the susceptible and resistant MIC breakpoints for RO 23-6240, the regression analysis-derived disk diffusion zone diameter breakpoints for the 5 micrograms disk are: Susceptible greater than or equal to 19 mm intermediate 16-18 mm, and resistant less than or equal to 15 mm.

Over 10,000 bacterial isolates were tested against ticarcillin alone or combined with clavulanic acid (2.0 micrograms/ml). Of 5,295 Enterobacteriaceae, 72% were susceptible to ticarcillin alone, whereas 91% were susceptible to the combination. Bacteroides fragilis and Bacteroides melaninogenicus isolates were more susceptible to the combination. The activity of ticarcillin against other microorganisms was not profoundly influenced.

DJ-6783 is a new keto carboxylic acid having an expanded antimicrobial activity when compared with nalidixic acid or cinoxacin. Its usable activity includes the following: Enterobacteriaceae (MIC90, less than or equal to 0.06-4.0 micrograms/ml), Acinetobacter species (MIC90, 0.25-1.0 microgram/ml), Pseudomonas species (MIC90, 1.0-2.0 micrograms/ml), P. aeruginosa (MIC90, 16 micrograms/ml), Staphylococcus species (MIC90, 1.0-32 micrograms/ml), Haemophilus influenzae (MIC900, less than or equal to 0.06 microgram/ml), and Neisseria species (MIC90 less than or equal to 0.06 microgram/ml). The Streptococcus species were resistant to DL-6783 with MIC50 ranging from 16 to greater than 32 micrograms/ml. The drug appears to be bactericidal, minimally influenced by increasing inocula, but resistant mutants can be selected by serial subinhibitory concentration passages of strains in DJ-6783. The resulting resistant organisms also have higher MICs to related drugs such as norfloxacin, cinoxacin, and nalidixic acid. DJ-6783 was the most active organic acid not having structural characteristics of the fluorinated 4-quinolones.

Cefotetan is a new, potent, 7 alpha-methoxy cephalosporin (cephamycin). The in vitro activity of cefotetan tested in a multiphasic, collaborative study against 12,260 consecutive clinical isolates and 448 selected isolates showed 93% of Enterobacteriaceae, 90% of methicillin-susceptible Staphylococcus aureus (broth dilution), 83% of Bacteroides fragilis, and 72% of non-enterococcal streptococci to be inhibited by less than or equal to 8 micrograms/ml. Beta-Lactamase-producing and -nonproducing Haemophilus influenzae strains were inhibited by less than or equal to 1.0 micrograms/ml. Cefotetan's inhibitory spectrum paralleled those of the newest generation of cephems and exceeded those of cefoxitin and cefamandole. No useful activity was present against Streptococcus faecalis or Pseudomonas aeruginosa. Cefotetan was bactericidal without significant inoculum effect and was highly resistant to hydrolysis by Richmond-Sykes types I, III, and IV beta-lactamases. Hydrolysis of the chromogenic cephalosporin PADAC (pyridine-2-azo-p-dimethylaniline cephalosporin) by type I beta-lactamases was markedly inhibited by concentrations of cefotetan similar to those of the potent inhibitor dicloxacillin. Analysis of agar disk diffusion for several disk potencies and broth dilution susceptibility tests by regression and error rate-bounding methods produced preliminary tentative zone standards (30-micrograms disk, using minimal inhibitory concentration breakpoints of less than or equal to 8 micrograms/ml susceptible and greater than 32 micrograms/ml resistant, or 75-micrograms disk, using minimal inhibitory concentration breakpoints of less than or equal to 16 micrograms/ml susceptible and greater than or equal to 64 micrograms/ml resistant) of greater than or equal to 18 mm susceptible, less than or equal to 14 mm resistant, and 15 to 17 mm indeterminate. Staphylococcus aureus testing with the 30-micrograms disk is not recommended.

In vitro studies were performed comparing ciprofloxacin (Bay o 9867) and norfloxacin with three related organic acids. Ciprofloxacin was two to eight times more active than norfloxacin against 658 bacterial isolates representing 30 species. For all species tested, ciprofloxacin MICs for 90% inhibition were less than or equal to 2.0 micrograms ml. Additional tests with 5,994 isolates detected only 37 (0.6%) strains resistant to 2.0 micrograms of ciprofloxacin per ml and 106 (1.8%) resistant to 1.0 micrograms/ml. Only 6 (0.1%) of the 5,994 strains were resistant to 16 micrograms of norfloxacin per ml, and 129 (2.1%) were resistant to 4.0 micrograms/ml. The majority of resistant strains were streptococci or Pseudomonas spp. Resistance among the Enterobacteriaceae was extremely rare (i.e., greater than 99.8% susceptible to both drugs.

The susceptibility of 7,763 clinical isolates at four medical centers to CI-934 and three comparative quinolones was tested. CI-934 was the most active compound against Gram-positive isolates, such as staphylococci (MIC 90 = 0.25 microgram/ml), and enterococci (MIC 90 = 0.5 microgram/ml). CI-934 was the least active of these drugs against Pseudomonas spp. (MIC 90 = greater than 8.0 micrograms/ml). Against all other organisms CI-934 was very effective, being most comparable with enoxacin. With a selected group of isolates, CI-934 demonstrated high activity against Haemophilus influenzae (MIC 90 = 0.06 microgram/ml), Neisseria meningitidis and N. gonorrhoeae (MIC 90 = 0.13 microgram/ml), Listeria monocytogenes (MIC 90 = 1.0 microgram/ml), methicillin-resistant staphylococci (MIC 90 = 0.13 microgram/ml), and modest activity against anaerobes. Disk diffusion susceptibility testing of CI-934 was evaluated using 3-, 5-, and 10-micrograms disks. Because of its lower interpretive error rate, the 3-micrograms disk is tentatively recommended. With less than or equal to 2 micrograms/ml and greater than 4 micrograms/ml as the susceptible and resistant MIC breakpoints, the corresponding 3-micrograms disk zone diameters breakpoints are greater than or equal to 15 mm and less than or equal to 11 mm. Because most isolates of Pseudomonas spp. are not susceptible to CI-934 and the zone size interpretive error rate is particularly high (33%) with Pseudomonas spp., we suggest that isolates of this genus not be tested for clinical purposes.

A six-laboratory collaborative study was performed in order to define quality control limits for microdilution tests with seven new beta-lactams (aztreonam, imipenem, ceftriaxone, ceftazidime, ceftizoxime, cefuroxime, and cefonicid). Four standard control strains were tested and the expected MIC limits for each of the appropriate drug-microorganism combinations were defined.

The in vitro susceptibilities of 260 strains of coagulase-negative staphylococci to penicillin G, oxacillin, nafcillin, methicillin, cephalothin, and seven non-beta-lactam antimicrobial agents were determined and compared with the susceptibilities of 54 strains of Staphylococcus aureus with known patterns of susceptibility. Penicillin G susceptibility for S. aureus, Staphylococcus epidermidis, Staphylococcus haemolyticus, and Staphylococcus hominis was readily determined by using beta-lactamase tests with induced cells and with a standardized microdilution test. MIC criteria for susceptibility used for S. aureus were applicable to the coagulase-negative species. Percentages of organisms susceptible were as follows: S. epidermidis, 7%; S. haemolyticus, 5%; and S. hominis, 47%. Oxacillin susceptibility for these four species was readily determined by using a modification of the microdilution test. MIC criteria for susceptibility used for S. aureus were applicable to S. haemolyticus and S. hominis, but alternate criteria were necessary for S. epidermidis. Percentages of organisms susceptible were as follows: S. epidermidis, 29%; S. haemolyticus, 36%; and S. hominis, 97%. Staphylococcus saprophyticus differed from the other staphylococcal species; all strains were beta-lactamase negative and were penicillin susceptible but had higher penicillin G MICs than did susceptible strains of the other species. There was total cross resistance among the penicillinase-resistant penicillins and cephalothin for the coagulase-negative staphylococci as well as for S. aureus; oxacillin MICs were more reliable than MICs of the other drugs or a standardized disk diffusion test for distinguishing resistant from susceptible strains. Vancomycin, rifampin, and ciprofloxacin were consistently active against all staphylococci. Erythromycin, clindamycin, gentamicin, and trimethoprim-sulfamethoxazole were more active against oxacillin-susceptible staphylococci than against oxacillin-resistant staphylococci.

Susceptibility testing of 7,775 recent clinical isolates from four medical centers showed Ro 15-8074 to be 2-to greater than 8-fold more active than either cefaclor or cefuroxime against the Enterobacteriaceae. Ro 15-8074 MICs for 50% of the strains tested were greater than or equal to 32 micrograms/ml for Staphylococcus spp., enterococci, Pseudomonas aeruginosa, and Pseudomonas maltophilia. beta-Lactamase hydrolysis experiments failed to demonstrate significant Ro 15-8074 inactivation by commonly encountered chromosomal or plasmid-mediated enzymes (P99, K1, K14, TEM, and CARB).