Markers of inflammation: data from the MOSAIC randomised trial of CPAP for minimally symptomatic OSA.

UNLABELLED: The Multi-centre Obstructive Sleep Apnoea Interventional Cardiovascular (MOSAIC) trial compared 6 months of CPAP therapy, versus no CPAP, in 391 patients with minimally symptomatic obstructive sleep apnoea (OSA). We now report some exploratory outcomes, markers of systemic inflammation (interleukin 6 (IL-6), IL-10, C reactive protein, tumour necrosis factor). We found no consistent changes (all p values >0.13). TRIAL REGISTRATION NUMBER: ISRCTN 34164388.

T cell phenotypes in patients with common variable immunodeficiency disorders: associations with clinical phenotypes in comparison with other groups with recurrent infections.

Common variable immunodeficiency disorders (CVID) are a group of heterogeneous conditions that have in common primary failure of B cell function, although numerous T cell abnormalities have been described, including reduced proliferative response and reduced regulatory T cells. This study compared the T cell phenotype of CVID patients subdivided into clinical phenotypes as well as patients with partial antibody deficiencies [immunoglobulin (Ig)G subclass deficiency and selective IgA deficiency], X-linked agammaglobulinaemia (XLA) and healthy and disease controls. Absolute numbers of T cell subpopulations were measured by four-colour flow cytometry: naive T cells, central and effector memory and terminally differentiated (TEM) T cells, using CD45RA and CCR7 expression. Early, intermediate and late differentiation status of T cells was measured by CD27/CD28 expression. Putative follicular T cells, recent thymic emigrants and regulatory T cells were also assessed. Significant reduction in naive CD4 T cells, with reduced total CD4 and recent thymic emigrant numbers, was observed in CVID patients, most pronounced in those with autoimmune cytopenias or polyclonal lymphoproliferation. These findings suggest a lack of replenishment by new thymically derived cells. CD8 naive T cells were reduced in CVID patients, most significantly in the autoimmune cytopenia subgroup. There was a reduction in early differentiated CD4 and CD8 T cells and increased CD8 TEM in the CVID patients, particularly autoimmune cytopenia and polyclonal lymphoproliferation subgroups, suggesting a more activated T cell phenotype, due perhaps to an antigen-driven process. XLA patients had significantly reduced putative follicular T cells, which may depend on B cells for survival, while no significant alterations were observed in the T cells of those with IgG subclass deficiency or selective IgA deficiency.

Impact of the HIV epidemic and Anti-Retroviral Treatment policy on lymphoma incidence and subtypes seen in the Western Cape of South Africa, 2002-2009: preliminary findings of the Tygerberg Lymphoma Study Group.

The Tygerberg Lymphoma Study Group was constituted in 2007 to quantify the impact of HIV on the pattern and burden of lymphoma cases in the Western Cape of South Africa which currently has an HIV prevalence of 15%. South Africa has had an Anti-Retroviral Treatment (ART) policy and a roll-out plan since 2004 attaining 31% effective coverage in 2009. This study is designed to qualify and establish the impact of HIV epidemic and the ARV roll-out treatment program on the incidence of HIV Related Lymphoma (HRL). Early data document that despite the ART roll out, cases of HRL are increasing in this geographical location, now accounting for 37% of all lymphomas seen in 2009 which is an increase from 5% in 2002. This is in contrast to trends seen in developed environments following the introduction of ART. Also noted are the emergence of subtypes not previously seen in this location such as Burkitt and plasmablastic lymphomas. Burkitt lymphoma is now the commonest HRL seen in this population followed by diffuse large B-cell lymphoma subtypes. The reasons for this observed increase in HRL are not ascribable to improved diagnostic capacity as the tertiary institute in which these diagnoses are made has had significant expertise in this regard for over a decade. We ascribe this paradoxical finding to an ART treatment environment that is ineffective for a diversity of reasons, paramount of which are poor coverage, late commencement of ART and incomplete viral suppression.

Effects of continuous positive airway pressure on systemic inflammation in patients with moderate to severe obstructive sleep apnoea: a randomised controlled trial.

BACKGROUND: Obstructive sleep apnoea syndrome (OSAS) has been associated with cardiovascular disease in epidemiological and observational studies. Continuous positive airway pressure (CPAP) is the treatment of choice for OSAS, but the impact of this intervention on systemic inflammation involved in the atherosclerotic process remains unclear. METHODS: 100 men with moderate-severe OSAS were randomised to therapeutic (n = 51) or subtherapeutic (n = 49) CPAP treatment for 4 weeks to investigate the effects of active treatment on inflammatory markers such as highly sensitive C reactive protein (hsCRP), interleukin (IL)6, interferon gamma (IFNgamma) and anti-inflammatory adiponectin. RESULTS: 4 weeks of therapeutic CPAP did not significantly change blood levels of hsCRP compared with the subtherapeutic control group (difference between median changes -0.24 mg/l (95% CI -0.88 to +0.24); p = 0.30). Plasma levels of IL6 and IFNgamma did not change significantly following therapeutic compared with subtherapeutic CPAP (difference between median changes +0.52 and -0.07 pg/ml (95% CI -0.72 to +1.94 and -0.81 to +0.44); p = 0.45 and p = 0.82, respectively). Furthermore, 4 weeks of therapeutic CPAP did not significantly change levels of adiponectin in plasma compared with the subtherapeutic control group (difference between median changes +0.05 pg/ml (95% CI -0.36 to +0.47); p = 0.84). If patients with hsCRP values above 8 mg/l at baseline were excluded, differences between the changes in hsCRP, IL6, IFNgamma and adiponectin after 4 weeks of CPAP were smaller, and again not statistically different between groups. CONCLUSIONS: 4 weeks of CPAP treatment has no beneficial effect on blood markers of inflammation and adiponectin in patients with moderate-severe obstructive sleep apnoea.

Circulating cell-derived microparticles in patients with minimally symptomatic obstructive sleep apnoea.

Moderate-severe obstructive sleep apnoea (OSA) has been associated with several pro-atherogenic mechanisms and increased cardiovascular risk, but it is not known if minimally symptomatic OSA has similar effects. Circulating cell-derived microparticles have been shown to have pro-inflammatory, pro-coagulant and endothelial function-impairing effects, as well as to predict subclinical atherosclerosis and cardiovascular risk. In 57 patients with minimally symptomatic OSA, and 15 closely matched control subjects without OSA, AnnexinV-positive, platelet-, leukocyte- and endothelial cell-derived microparticles were measured by flow cytometry. In patients with OSA, median (interquartile range) levels of AnnexinV-positive microparticles were significantly elevated compared with control subjects: 2,586 (1,566-3,964) microL(-1) versus 1,206 (474-2,501) microL(-1), respectively. Levels of platelet-derived and leukocyte-derived microparticles were also significantly higher in patients with OSA (2,267 (1,102-3,592) microL(-1) and 20 (14-31) microL(-1), respectively) compared with control subjects (925 (328-2,068) microL(-1) and 15 (5-23) microL(-1), respectively). Endothelial cell-derived microparticle levels were similar in patients with OSA compared with control subjects (13 (8-25) microL(-1) versus 11 (6-17) microL(-1)). In patients with minimally symptomatic obstructive sleep apnoea, levels of AnnexinV-positive, platelet- and leukocyte-derived microparticles are elevated when compared with closely matched control subjects without obstructive sleep apnoea. These findings suggest that these patients may be at increased cardiovascular risk, despite being minimally symptomatic.

Selective sputum cultures. A bronchial culture technique using a modified nasotracheal suction catheter with a sterile, inner telescoping cannula.

The contamination of expectorated or catheter-aspirated sputum specimens by pathogenic microorganisms which have colonized the nose and oropharynx remains a formidable obstacle to the accurate interpretation of sputum cultures. This problem is encountered in all forms of acute and chronic bronchopulmonary infection. A standard suctioning technique via a nasotracheal catheter has been modified with a telescoping sterile inner cannula to obtain uncontaminated bronchopulmonary secretions for culture. Bacteriologic results of selective bronchial cultures obtained in 18 patients following major chest surgery have provided important considerations concerning the prophylactic use of antibiotics. The telescoping cannula method is a simple, safe, and practical means of selectively monitoring the bacteriologic flora of the lower respiratory tract.

Aerosol administration of fenoterol hydrobromide (Th 1165a) in subjects with reversible obstructive airway disease.

Bronchodilatory and side effects of fenoterol hydrobromide (Th1165a; hydroxyphenylorciprenaline; Berotec) and isoproterenol given by inhalation were compared in a double-blind crossover study involving 20 volunteer subjects with reversible obstructive disease of the airways. Subjects inhaled medications from aerosol canisters containing fenoterol hydrobromide (0.1 mg, 0.2 mg, or 0.4 mg) or isoproterenol (0.15 mg) or an inert placebo propellant in a random sequence of five testing days. All active drugs substantially increased the forced expiratory volume in one second, the mean forced expiratory flow during the middle half of the forced vital capacity, and the specific conductance. The onset of bronchodilation after both fenoterol and isoproterenol was rapid, but the effect from fenoterol lasted much longer, up to eight hours. None of the medications cuased significant tachycardia or hypertension. After inhalation of 0.1 mg of fenoterol hydrobromide, none of the subjects reported nervousness, headache, tremor, or nausea, incontrast with results reported for isoproterenol, higher aerosol doses fo fenoterol, or oral administration of fenoterol. No additional therapeutic benefit was found in the administration of higher doses of fenoterol.

Neonatal airway colonization with gram-negative bacilli: association with severity of bronchopulmonary dysplasia.

BACKGROUND: Airway colonization with Gram-negative bacilli (GNB) and Gram-positive cocci (GPC) is common in mechanically ventilated neonates. Whether GNB are related to nosocomial bloodstream infection (BSI) and/or to the severity of bronchopulmonary dysplasia (BPD) is unknown. METHODS: We prospectively examine this relationship using a cohort design. Data from 260 < or = 1250-g birth weight inborn infants (1991 to 1995) intubated > or = 2 weeks included 917 serial tracheal cultures and 583 blood cultures. The severity of BPD was assessed by duration of mechanical ventilation, oxygen dependency at 36 weeks of postconceptional age and the use of home oxygen supplementation. RESULTS: After 2 weeks of ventilation, 80% of the infants were colonized with GPC (Staphylococus epidermidis and Staphylococcus haemolyticus in 90% of the cases). Superimposed on 36% of these infants was GNB airway colonization with Klebsiella pneumoniae (25%), Enterobacter cloacae (25%), Escherichia coli (25%), Pseudomonas aeruginosa (10%), Serratia marcescen (10%), Acinetobacter baumannii and Haemophilus influenzae (5%). Comparison between 174 GPC- and 86 GNB-colonized infants showed that demographics, birth weight, gestational age, perinatal risk factors and mortality were similar. Fifteen percent of GNB-colonized infants developed BSI caused by GNB and 14% developed BSI caused by GPC. No significant temporal relationship between airway colonization and BSI was noted. GNB infants were ventilated longer and required oxygen at 36 weeks of postconceptional age and home oxygen supplementation twice as often as infants colonized only with GPC. GNB colonization was a predictor of severe BPD after controlling for ventilation. Ureaplasma colonization occurred in 28% of GNB-colonized and 33% of noncolonized infants and was not a predictor of BPD severity. CONCLUSION: GNB airway colonization creates a moderate risk for BSI. Antibiotic treatment does not regularly eradicate GNB. GNB airway colonization is associated with severe BPD, but further studies will be necessary before therapeutic efforts to eradicate GNB from the airways should be undertaken.

Bloodstream infections in a neonatal intensive-care unit: 12 years' experience with an antibiotic control program.

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.

Mycobacterium fortuitum infection of a Hickman catheter site.

A patient with histiocytic lymphoma who developed a Hickman catheter exist site infection due to Mycobacterium fortuitum is described. Due to the risk of dissemination in immunosuppressed patients and the resistance to antibiotic therapy, rapid-growing mycobacteria should be considered when gram-positive bacilli are associated with infections in patients with these catheters.

Failure of systemic antibiotics to eradicate gram-negative bacilli from the airway of mechanically ventilated very low-birth-weight infants.

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.

Ventilator-associated pneumonia in very low-birth-weight infants at the time of nosocomial bloodstream infection and during airway colonization with Pseudomonas aeruginosa.

PURPOSE: To study retrospectively the incidence of ventilator-associated pneumonia (VAP) at the time of Pseudomonas aeruginosa nosocomial bloodstream infection (BSI) and at the time of P aeruginosa airway colonization. MATERIALS AND METHODS: Fifteen very low-birth-weight infants who had P aeruginosa BSI and 33 others who did not but who had P aeruginosa airway-colonization were studied. We correlated clinical data, blood cultures (BCs), and tracheal cultures (TCs) with radiologic findings from radio-graphs taken within 2 days before, the day of, and 1 day after BCs or TCs were first positive for P aeruginosa. Chest radiographs were graded by using semiquantitative scores for bronchopulmonary dysplasia and for pneumonia. RESULTS: Mean birth weight, gestational age, and age when BC or TC became positive were similar for patients with BSI and colonization. At the time of BSI, 2 infants had airway colonization with P aeruginosa; the TCs of the remaining 13 grew P aeruginosa as a new pathogen. Thirteen of 15 patients with BSI, but none of 33 infants with colonization, died within 2 days of positive BC. VAP was diagnosed in 13 of 15 patients with BSI and in 3 of 33 infants with colonization. CONCLUSION: Mechanically ventilated very low-birth-weight infants whose TCs yield P aeruginosa but whose BCs remain negative infrequently have VAP are presumed airway-colonized and are expected to survive. Conversely, VAP is likely to be found when BCs and TCs simultaneously grow P aeruginosa, and high mortality is anticipated.

Does extra-amniotic infection cause preterm labor? Gas-liquid chromatography studies of amniotic fluid in amnionitis, preterm labor, and normal controls.

Gas-liquid chromatography (GLC) was used to identify short-chain organic acid byproducts of bacterial metabolism in amniotic fluid from seven normal control patients, six women with overt amnionitis, and six preterm labor patients. Microbiologic culture for aerobic and anaerobic bacteria was also carried out. Positive GLC findings were generally associated with positive cultures, except in five of the preterm labor patients whose GLCs were positive despite negative cultures. The origin of the short-chain organic acids found in these women is unclear; extra-amniotic bacterial growth may explain this finding.

The utility of non-beta-lactam antimicrobial MICs as markers to distinguish oxacillin-resistant from oxacillin-susceptible strains of Staphylococcus epidermidis.

Among 6,068 strains of Staphylococcus epidermidis, 75.5% were oxacillin-resistant. Oxacillin-susceptible strains were more frequently susceptible to erythromycin, clindamycin, ciprofloxacin, trimethoprim/sulfamethoxazole, gentamicin, and tetracycline than oxacillin-resistant strains. With the exception of erythromycin, non-beta-lactam MICs were less discriminatory for identifying oxacillin-resistant strains with oxacillin MICs < or = 2 micrograms/ml than for those with oxacillin MICs > or = 4 micrograms/ml.

Imipenem (N-formimidoyl thienamycin): in vitro antimicrobial activity and beta-lactamase stability.

In vitro studies with imipenem (N-formimidoyl thienamycin or MK0787) were performed with 8481 clinical isolates in three separate medical centers. More extensive comparative studies were also performed with 605 representative isolates, comparing imipenem to six other beta-lactams. Although the newer beta-lactams were often more active against susceptible species, imipenem demonstrated the broadest spectrum of antibacterial activity, with MIC 90s less than or equal to 4.0 micrograms/ml for all species tested except Pseudomonas maltophilia and P. cepacia. Imipenem was very active against all streptococci and staphylococci, in contrast to the third-generation cephalosporins. There was no evidence of cross-resistance between imipenem and the cephalosporins or penicillins. Resistance to hydrolysis by seven beta-lactamase preparations was documented for imipenem, cefotaxime, and moxalactam. Like many other beta-lactams, imipenem inhibited the Type I beta-lactamase produced by Enterobacter cloacae. Other beta-lactamases from gram-negative bacilli were also inhibited by high concentrations of imipenem.

Antimicrobial activity of Ro 19-5247 (T-2525), a new oral cephalosporin, tested against 7,745 recent clinical isolates.

The susceptibility testing of 7,745 recent clinical isolates from four medical centers showed Ro 19-5247 to be eight- to greater than 64-fold more active than cephalexin against the Enterobacteriaceae. Ro 19-5247 was comparable with cephalexin in anti-staphylococcal activity (MIC50, 4.0 micrograms/ml) and fourfold more active than cefixime. None of the oral cephalosporins were effective (MIC50, greater than 32 micrograms/ml) against enterococci, Pseudomonas aeruginosa and P. maltophilia. beta-lactamase hydrolysis experiments failed to demonstrate significant Ro 19-5247 inactivation by ten commonly encountered chromosomal- or plasmid-mediated enzymes (P99, K1, K14, TEM, CARB, OXA).

In vitro evaluation of cefixime (FK027, FR17027, CL284635): spectrum against recent clinical isolates, comparative antimicrobial activity, beta-lactamase stability, and preliminary susceptibility testing criteria.

Cefixime, a new orally absorbed cephalosporin, was compared by in vitro testing with other oral beta-lactams, including cephalexin, cefaclor, cefuroxime, amoxicillin, and amoxicillin + clavulanate. Enterobacteriaceae were inhibited by lower concentrations of cefixime than any of the reference drugs; 90% and 95% were inhibited by less than or equal to 1.0 and less than or equal to 8.0 micrograms/ml, respectively. Cefixime was the least active among these drugs against staphylococci, with only 31% of 1106 strains inhibited by less than or equal to 8.0 micrograms/ml and less than 1% by less than or equal to 1.0 microgram/ml. Enterococci and pseudomonads were not susceptible to any of the drugs tested. Penicillin-resistant pneumococci were relatively resistant to cefixime, but penicillin-susceptible pneumococci were very susceptible to cefixime. Other streptococci were generally susceptible to all compounds tested, with relative activities of amoxicillin greater than cefaclor and cefuroxime greater than cefixime greater than cephalexin. Cefixime was inactive against Bacteroides species. A slight inoculum effect occurred with cefixime with inocolum concentrations varying from 10(5) to 10(6) colony forming units per milliliter, but this was more marked at 10(7) colony forming units per milliliter. Cefixime was resistant to hydrolysis by seven common beta-lactamases. It inhibited the hydrolysis of nitrocefin only by type 1 cephalosporinases. The disk diffusion zone diameter breakpoints for the 30-micrograms cefixime disk were determined by regression analysis to be greater than or equal to 27 mm (susceptible) and less than or equal to 23 mm (resistant), respectively corresponding to minimal inhibitory concentration breakpoints of less than or equal to 1.0 and greater than or equal to 4.0 micrograms/ml. Because of the high interpretive error rate (13.8%) and the occurrence of these breakpoints on the parabolic portion of the regression curve, we recommend further evaluation of cefixime disks with lower potencies.

In vitro activity of carumonam (RO 17-2301), BMY-28142, aztreonam, and ceftazidime against 7,620 consecutive clinical bacterial isolates.

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.

In vitro activity of DJ-6783 (a keto carboxylic acid) compared with six other orally administered antimicrobial agents.

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.

Antimicrobial activity of U-76,252 (CS-807), a new orally administered cephalosporin ester, including recommendations for MIC quality control.

U-76,253A (R-3746), the active metabolite of the new cephalosporin ester, U-76,252 (CS-807), was tested against 4,742 fresh clinical isolates from four large medical centers. U-76,253A was very active against nearly all species of Enterobacteriaceae (87.7% inhibited at less than or equal to 4.0 micrograms/ml). Staphylococcus spp., and the streptococci. The U-76,253A spectrum was superior to the comparison orally administered cephalosporins (cephalexin, cephradine, cefaclor). Pseudomonas spp., Acinetobacter spp., and the enterococci were resistant to U-76,253A and the other tested drugs. Broth microdilution MIC quality control (QC) limits were established for U-76,253A in a multilaboratory investigation using a minimum of 125 MIC determinations per organism. The following MIC QC ranges were recommended; Escherichia coli (ATCC 25922) = 0.25-1.0 micrograms/ml, Staphylococcus aureus (ATCC 29213) = 2.0-4.0 micrograms/ml and Pseudomonas aeruginosa (ATCC 27853) = greater than 32 micrograms/ml.