MIC 90s Research Articles

ENDOPHTHALMITIS CAUSED BY PSEUDOMONAS AERUGINOSA

To report the clinical features, antibiotic susceptibilities, and visual outcomes associated with endophthalmitis caused by Pseudomonas aeruginosa. A consecutive case series. Microbiology database records were retrospectively reviewed for all patients with endophthalmitis caused by P. aeruginosa from January 1, 2002, to December 31, 2012, at a large university referral center. The corresponding clinical records were then reviewed to evaluate the endophthalmitis clinical features and treatment outcomes. In the 12 patients identified, clinical settings included postcataract surgery (n = 4), postpenetrating keratoplasty (n = 3), endogenous source (n = 2), post-pars plana vitrectomy (n = 1), trabeculectomy bleb-associated setting (n = 1), and glaucoma drainage implant-associated setting (n = 1). All patients presented with hypopyon. Presenting visual acuity was hand motions or worse in all cases. All isolates were susceptible to ceftazidime and levofloxacin. When comparing isolates in this study with isolates from a previous study (1987 to 2001), the minimal inhibitory concentration required to inhibit 90% of isolates (MIC 90, in micrograms per milliliter) remained the same for ceftazidime (8), ciprofloxacin (0.5), imipenem (4), tobramycin (0.5), and amikacin (4). Initial treatment strategies were vitreous tap and injection (n = 9) and pars plana vitrectomy with intravitreal antibiotics (n = 3). Final visual acuity was light perception or worse in 11 of the 12 patients (92%). Five patients underwent enucleation (42%). All isolates were susceptible to ceftazidime and levofloxacin, and all MIC 90s for isolates in the current period compared with isolates from 1987 to 2001 remained identical. Despite early and appropriate treatment, outcomes were generally poor with a high rate of enucleation.

ENDOPHTHALMITIS CAUSED BY SERRATIA MARCESCENS: Clinical Features, Antibiotic Susceptibilities, and Treatment Outcomes.

To report the clinical features, antibiotic sensitivities, and visual outcomes associated with endophthalmitis caused by Serratia marcescens. A consecutive case series of patients with vitreous culture-positive endophthalmitis caused by S. marcescens from July 1, 1993, to June 30, 2012, at a large university referral center. Findings from this study were compared with those of a previous study (January 1980-June 1993) from our institution. Of the 10 study patients who were identified, clinical settings included trabeculectomy bleb-associated (n = 3), post-cataract surgery (n = 2), post-penetrating keratoplasty (n = 2), post-scleral buckle (n = 1), glaucoma drainage implant-associated (n = 1), and post-keratoprosthesis (n = 1). Clinical features included pain (n = 10) and hypopyon (n = 5). Presenting visual acuity was hand motions or worse in seven cases. All isolates were sensitive to gentamicin, ceftazidime, imipenem, and levofloxacin. The MIC 90s of isolates for antibiotics tested in the current period compared with isolates from January 1980 to June 1993 were unchanged. All isolates were resistant to vancomycin. Initial treatment strategies were vitreous tap and intravitreal antibiotic injection (n = 8), pars plana vitrectomy with intravitreal antibiotic injection (n = 1), and evisceration (n = 1). When repeat vitreous fluid was obtained, persistent positive cultures were present in 1 (10%) of 10 patients in this study, compared with 5 (50%) of 10 patients in the previous study. Final visual acuity was no light perception in 6 of 10 patients (60%). Outcomes were generally poor with a high rate of complete visual loss in the affected eye.

Sesquiterpene lactones from Gynoxys verrucosa and their anti-MRSA activity

Ethnopharmacological relevance Because of its virulence and antibiotic resistance, Staphylococcus aureus is a more formidable pathogen now than at any time since the pre-antibiotic era. In an effort to identify and develop novel antimicrobial agents with activity against this pathogen, we have examined Gynoxys verrucosa Wedd (Asteraceae), an herb used in traditional medicine in southern Ecuador for the treatment and healing of wounds. Materials and methods The sesquiterpene lactones leucodine ( 1) and dehydroleucodine ( 2) were extracted and purified from the aerial parts of Gynoxys verrucosa, and their structure was elucidated by spectroscopic methods and single-crystal X-ray analysis. The in vitro anti-microbial activity of Gynoxys verrucosa extracts and its purified constituents was determined against six clinical isolates including Staphylococcus aureus and Staphylococcus epidermidis strains with different drug-resistance profiles, using the microtiter broth method. Results Compound 1 has very low activity, while compound 2 has moderate activity with MIC 50s between 49 and 195 μg/mL. The extract of Gynoxys verrucosa has weak activity with MIC 50s between 908 and 3290 μg/mL. Conclusions We are reporting the full assignment of the 1H NMR and 13C NMR of both compounds, and the crystal structure of compound 2, for the first time. Moreover, the fact that compound 2 has antimicrobial activity and compound 1 does not, demonstrates that the exocyclic conjugated methylene in the lactone ring is essential for the antimicrobial activity of these sesquiterpene lactones. However, the weak activity observed for the plant extracts, does not explain the use of Gynoxys verrucosa in traditional medicine for the treatment of wounds and skin infections.

Susceptibility of Helicoverpa zea and Heliothis virescens (Lepidoptera: Noctuidae) to Vip3A insecticidal protein expressed in VipCot™ cotton

Susceptibility of laboratory and field colonies of Helicoverpa zea (Boddie) and Heliothis virescens F. to Vip3A insecticidal protein was studied in diet incorporation and diet overlay assays from 2004 to 2008. Responses of field populations were compared to paired responses of University of Arkansas laboratory susceptible H. zea (LabZA) and H. virescens (LabVR) colonies. After 7 d of exposure, observations were made on number of dead larvae ( M) and the number of larvae alive but remaining as first instars (L1). Regression estimates using M (LC 50) and M plus L1 (MIC 50) data were developed for laboratory and field populations. Susceptibility of laboratory and field populations exposed to Vip3A varied among different batches of protein used over the study period. Within the same batch of Vip3A protein, susceptibilities of laboratory colonies of both species (LabZA and LabVR) were similar. Field colonies were significantly more susceptible to Vip3A than the respective reference colonies of both species. Within field populations, susceptibility to Vip3A varied up to 75-fold in H. zea and 132-fold in H. virescens in LC 50 estimates. Variabilities in MIC 50s were up to 59- and 11-fold for H. zea and H. virescens, respectively.

Genotypes of macrolide-resistant pneumococci from children in southwestern Japan: raised incidence of strains that have both erm(B) and mef(A) with serotype 6B clones

MICs of penicillin G, erythromycin, clarithromycin, clindamycin, azithromycin, and telithromycin were tested for 189 clinical isolates collected during 2002 to 2005 from children in southwestern Japan. Serotyping and polymerase chain reaction for presence of erm(B) and mef(A) were performed. All strains with erm(B) + mef(A) were analyzed by pulsed-field gel electrophoresis (PFGE) and compared to 3 global clones: Spain 23F-1; Spain 9V-3 and its variant -14; a South Korean strain same as Taiwan 19F-14 clone and 5 strains with erm(B) + mef(A) from other countries. Of the 173 macrolide-resistant (erythromycin MIC ≥0.5 μg/mL) strains, 104 (60.1%) had erm(B), 47 (27.2%) had mef(A), and 22 (12.7%) had erm(B) + mef(A). Strains expressing erm(B) or both erm(B) and mef(A) had high macrolide MIC 90s (>64 μg/mL), except telithromycin (MIC 90, 0.25 μg/mL). Of the 22 erm(B) + mef(A) strains, 10 had 4 distinct PFGE patterns and were mainly serotype 6B clones, which differed from those described in previous reports; 5 other strains had unique profiles.

Emergence of multidrug-resistant Salmonella spp. and isolates with reduced susceptibility to ciprofloxacin in Kuwait and the United Arab Emirates

Kuwait and United Arab Emirates (UAE) are 2 countries with worldwide significance in the context of global epidemiology of antimicrobial resistance. The extent of drug resistance in Salmonella spp. isolated from these countries was investigated by determining their susceptibility to 9 antibiotics using the E-test method. Amikacin, cefotaxime, ceftriaxone, ciprofloxacin, and gentamicin had excellent activities against all Kuwait and UAE isolates with MIC 90s ranging between 0.056 and 4.5 μg/mL. The resistance rates in Kuwait and UAE to ampicillin were 26.5% and 17.1%, cefotaxime/ceftriaxone 1.6% and 1.6%, ciprofloxacin 1.2% and 0.8%, chloramphenicol 5.6% and 5.7%, and trimethoprim–sulfamethoxazole 26.1% and 8.9%, respectively. A total of 9.8% of the Kuwait isolates were multidrug resistant versus 4.1% of UAE isolates. Reduced susceptibility to ciprofloxacin was observed in 14.2% and 7.4% of the nontyphoidal Salmonella, respectively, as were in 44% of Salmonella enterica serovar typhi and 66.7% Salmonella paratyphi. Salmonella spp. with reduced quinolones susceptibility have emerged in the Gulf region, and this is of concern as it may compromise the treatment of infections caused by invasive strains.

Antimicrobial resistance of 114 porcine isolates of Campylobacter coli

Campylobacter species were isolated from 24 pig farms in 10 different regions of Korea, and were assayed with regard to their susceptibility to eight antimicrobial agents. A total of 114 Campylobacter isolates from 572 intestinal samples were all identified as C. coli via both classical methods and molecular methods, including 16S rDNA sequence analysis and polymerase chain reactions (PCR) using specific primer sets for the hippuricase gene and the aspartokinase gene, designed to differentiate C. coli from C. jejuni. Minimal inhibitory concentrations of seven antimicrobial agents were determined via agar dilution: the MIC 90s were 64 μg/ml for ampicillin, 8 μg/ml for chloramphenicol, 64 μg/ml for ciprofloxacin, 16 μg/ml for enrofloxacin, ≥ 128 μg/ml for erythromycin, ≥ 128 μg/ml for gentamicin, and ≥ 128 μg/ml for tetracycline. The proportion of isolates resistant to each antimicrobial agent was as follows: 28.9% for ampicillin, 2.6% for chloramphenicol, 84.2% for ciprofloxacin, 83.3% for enrofloxacin, 46.5% for erythromycin, 20.2% for gentamicin, and 56.1% for tetracycline. All 114 isolates were found to be resistant to at least one antimicrobial agent, and 61 isolates (53.5%) were found to be multi-drug resistant (resistant to more than three antimicrobial agents in different classes).

Antimicrobial susceptibility of extended-spectrum β-lactamase producers and multidrug-resistant Acinetobacter baumannii throughout the United States and comparative in vitro activity of tigecycline, a new glycylcycline antimicrobial

As part of the Tigecycline Evaluation and Surveillance Trial, isolates of Escherichia coli, Klebsiella pneumoniae, and Acinetobacter baumannii were collected in the United States between January 2004 and January 2006. Determinations of antimicrobial susceptibility and extended-spectrum β-lactamase (ESBL) production were carried out according to the Clinical and Laboratory Standards Institute guidelines. A high percentage of ESBL-producing K. pneumoniae (≥19.0%) was detected in New Jersey, Massachusetts, New York, and Missouri, and for E. coli, in the District of Columbia (9.5%). Against ESBL-producing isolates, the lowest MIC 90s were for tigecycline (0.5–2 μg/mL) and imipenem (0.5–8 μg/mL). Overall, 282 (27.5%) A. baumannii isolates were resistant to ≥3 antimicrobial classes. The most common phenotype (33.0%) was resistance to cefepime, ceftazidime, ceftriaxone, levofloxacin, and piperacillin–tazobactam. Against multidrug-resistant A. baumannii, tigecycline and minocycline were the most active agents (MIC 90, 2 and 8 μg/mL, respectively).

In vitro activity of oritavancin (LY333328), vancomycin, clindamycin, and metronidazole against Clostridium perfringens, Propionibacterium acnes, and anaerobic Gram-positive cocci

Using an agar dilution method, we determined the in vitro activity of oritavancin, vancomycin, clindamycin and metronidazole against 114 unique clinical isolates of Gram-positive anaerobes. MIC 90s (μg/mL) for oritavancin were as follows: Clostridium perfringens 1.0, Propionibacterium acnes 0.25, Peptostreptococcus anaerobius 0.25, Peptoniphilus asaccharolyticus 0.5, Finegoldia magna 0.25, Micromonas. micros 0.25, and Anaerococcus prevotii 0.25. On a weight basis, oritavancin is slightly more active than vancomycin against the strains tested. The oritavancin MICs are comparable to those previously reported against staphylococci and enterococci. Oritavancin shows excellent potential for treatment of infections containing Gram-positive anaerobes such as these.

In vitro activity of ramoplanin and comparator drugs against anaerobic intestinal bacteria from the perspective of potential utility in pathology involving bowel flora

Susceptibility of intestinal bacteria to various antimicrobial agents in vitro, together with levels of those agents achieved in the gut, provides information on the likely impact of the agents on the intestinal flora. Orally administered drugs that are poorly absorbed may be useful for treatment of intestinal infections and for certain other situations in which intestinal bacteria may play a role. The antimicrobial activity of ramoplanin (MDL 62,198) against 928 strains of intestinal anaerobic bacteria was determined using the NCCLS-approved Wadsworth brucella laked-blood agar dilution method. The activity of ramoplanin was compared with that of ampicillin, bacitracin, metronidazole, trimethoprim/sulfamethoxazole (TMP/SMX), and vancomycin. The organisms tested included Bacteroides fragilis group ( n=89), other Bacteroides species ( n=16), other anaerobic Gram-negative rods ( n=56) anaerobic cocci ( n=114), Clostridium species ( n=426), and non-sporeforming anaerobic Gram-positive rods ( n=227). The overall MIC 90s of ramoplanin, ampicillin, bacitracin, metronidazole, and vancomycin were 256, 32, 128, 16, and 128 mcg/ml, respectively. Ramoplanin was almost always highly active vs. Gram-positive organisms and relatively poor in activity against Gram-negative organisms, particularly Bacteroides, Bilophila, Prevotella, and Veillonella. Vancomycin was quite similar to ramoplanin in its activity. Ampicillin was relatively poor in activity vs. organisms that often produce beta-lactamase, including most of the Gram-negative rods as well as Clostridium bolteae and C. clostridioforme. Bacitracin was relatively poor in activity against most anaerobic Gram-negative rods, but better vs. most Gram-positive organisms. Metronidazole was very active against all groups other than bifidobacteria and some strains of other types of non-sporeforming Gram-positive bacilli. TMP/SMX was very poorly active, with an MIC 90 of >2048 mcg/ml.

Topical antibacterial therapy for mycobacterial keratitis: Potential for surgical prophylaxis and treatment

Background: Mycobacterium chelonae and Mycobacterium fortuitum are the 2 most commonly implicated species of nontuberculous myoobacteria in cases of bacterial keratitis. Objectives: This article summarizes available data on the in vitro antibacterial activity against M chelonae or M fortuitum of 2 agents—amikacin and clarithromycin—that have been used in the treatment of bacterial keratitis. In addition, the article reviews the in vitro activity of 5 commercially available topical ocular fluoro-quinolones (in order of availability, ciprofloxacin, ofloxacin, levofloxacin, gatifloxacin, and moxifloxacin) that may have potential in the surgical prophylaxis and treatment of keratitis caused by M chelonae or M fortuitum. Methods: A search of the English-language literature indexed on the MEDLINE, Life Sciences, EMBASE, BIOSIS, and Pharmaprojects databases from 1966 to October 7, 2003, was conducted using the terms Mycobacterium chelonae, Mycobacterium fortuitum, bacterial keratitis, topical antibiotic therapy, ocular infection-mycobacteria, and LASIK infections. Data on the minimum concentrations at which 90% of isolates were inhibited (MIC 90s) were reviewed and compared. Results: In the literature reviewed, the MIC 90 against M fortuitum was from 1 to 16 μg/mL for amikacin, from ≤2 to ≥8 μg/mL for clarithromycin, from 0.1 to 1 μg/mL for ciprofloxacin, from 0.5 to 3.13 μg/mL for ofloxacin, and ≤2 μg/mL for levofloxacin. The results were similar against M chelonae. The fourth-generation fluoroquinolones—gatifloxacin and moxifloxacin—had similar MIC 90s against M fortuitum (both, 0.2 to 1 μg/mL); however, moxifloxacin had greater activity than gatifloxacin against M chelonae (minimum inhibitory concentration range: moxifloxacin, ≤1 to 1.6 μg/mL; gatifloxacin, 3.2 to 6.25 μg/mL). Conclusions: Topical fluoroquinolones may be beneficial for ocular surgical prophylaxis and for the treatment of keratitis caused by M chelonae or M fortuitum. Based on their reported MIC 90s, none of the antibacterials reviewed had greater in vitro activity than moxifloxacin. In addition, moxifloxacin had greater in vitro activity than gatifloxacin against M chelonae, one of the predominant nontuberculous mycobacterial species involved in bacterial keratitis. Pending the conduct of controlled clinical studies, these findings suggest that moxifloxacin may have utility in the prevention and treatment of atypical mycobacterial keratitis.

Inhibitory and bactericidal activities of gemifloxacin and other antimicrobials against Mycoplasma pneumoniae

The MIC of gemifloxacin was compared with that of sparfloxacin, levofloxacin, moxifloxacin, gatifloxacin, ciprofloxacin, doxycycline, erythromycin, azithromycin and clarithromycin using 97 clinical isolates of Mycoplasma pneumoniae. MBCs of fluoroquinolones were determined for a subgroup of 12 isolates. Macrolides were the most potent agents with MIC 90s for all drugs ⩽0.001 mg/l. The doxycycline MIC 90 was 0.5 mg/l. Gemifloxacin MICs ranged from ⩽0.001 to 0.25 mg/l. The gemifloxacin MIC 90 (0.125 mg/l) was equivalent to moxifloxacin and gatifloxacin, was 2-fold lower than sparfloxacin, 8-fold lower than levofloxacin and 32-fold lower than ciprofloxacin. MBCs for gemifloxacin were predominantly within 2–4 times the corresponding MIC values, indicating a bactericidal effect.

The in vitro effects of faropenem on lower respiratory tract pathogens isolated in the United Kingdom

Faropenem is a new oral penem with a structure different from current β-lactams including carbapenems. The susceptibility of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis to faropenem, a macrolide, a β-lactam, a β-lactam/β-lactamase inhibitor combination and two fluoroquinolones was investigated. S. pneumoniae was the most susceptible of the three species to faropenem. The MIC 90s of faropenem against M. catarrhalis and H. influenzae were 0.5 and 1 mg/l, respectively. They were similar to amoxiclav (MIC 90s of 0.25 and 0.5 mg/l). The quinolones showed strong activity against H. influenzae. A cluster analysis of the activities of amoxycillin and faropenem demonstrated a direct relationship between the two antimicrobial agent's activities and resistance profiles against both S. pneumoniae and H. influenzae.

Comparaison de l’activité in vitro de la moxifloxacine, de l’ofloxacine, de la ciprofloxacine, de la clindamycine, du métronidazole et de six β-lactamines vis-à-vis des anaérobies stricts

The in vitro activity of moxifloxacin was compared to that of ofloxacin, ciprofloxacin, clindamycin, metronidazole and 6 β-lactams (amoxicillin, amoxicillin + clavulanic acid, ticarcillin, ticarcillin + clavulanic acid, cefotetan and imipenem) for a selected group of anaerobes isolated from human clinical samples. MICs were determined by the reference M 11 A4 agar dilution method of the NCCLS. Moxifloxacin demonstrated good activity against the 76 strains of the Bacteroides fragilis group ; MIC 50 was 0.5 mg/l. MIC 50s of imipenem and metronidazole were 0.125 mg/l, and 0.5 mg/l, respectively. All strains of Porphyromonas, Prevotella, Fusobacterium and Peptostreptococcus were inhibited by moxifloxacin concentrations of ≤ 1mg/l. Out of 159 anaerobes, moxifloxacin inhibited 93.7, 94.9 and 98% of the strains investigated at concentrations of 1, 2 and 4 mg/l respectively. Moxifloxacin, unlike other fluoroquinolones, demonstrated high activity against strains of the B. fragilis group and Clostridum sp. It was more potent than ofloxacin and ciprofloxacin against Gram positive rods and anaerobic cocci. Given the broad spectrum of moxifloxacin against anaerobes, future clinical studies will be required to determine the role of this agent for the treatment of anaerobic infections.

In vitro anti-anaerobic activity of the cephalosporin derivative RWJ 54428, compared to seven other compound

Agar dilution MIC was used to test the activity of RWJ 54428, a new cephalosporin derivative, compared to imipenem, meropenem, ceftriaxone, piperacillin, piperacillin–tazobactam, clindamycin and metronidazole against 363 anaerobes isolated from clinical specimens. RWJ 54428 had low MICs against most β-lactamase-negative Gram-negative rods, and all Gram-positive strains except Clostridium difficile. Imipenem and meropenem had the lowest MICs (MIC50s of 0.125 mg/L and MIC90s of 1.0 mg/L). Piperacillin–tazobactam, clindamycin and metronidazole were active against most strains, and ceftriaxone was active mainly against β-lactamase-negative organisms.

In vitro activity of 15 antimicrobial agents against clinical isolates of Clostridium difficile in Kuwait

A total of 73 clinical isolates of Clostridium difficile isolated from stool/rectal swabs of patients admitted to the intensive care units at Mubarak Hospital, Ibn Sina Hospital Burn unit and Haematology wards at the Kuwait Cancer Control Centre, were investigated for their susceptibility to 15 antibiotics using the Etest. Amoxycillin–clavulanic acid, ampicillin, meropenem, metronidazole, penicillin, piperacillin, piperacillin/tazobactam, teicoplanin and vancomycin had excellent activities with MIC 90s of 0.38, 0.5, 1, 0.19, 1.5, 2, 3, 0.25 and 0.75 mg/l, respectively. Of the 73 C. difficile isolates, 86% were resistant to imipenem (MIC 90 >32 mg/l) and almost 97% were resistant to trovafloxacin (MIC 90>256 mg/l). Forty eight percent of the isolates were resistant to clindamycin. A total of 18 isolates were highly clindamycin-resistant with an MIC of >256 mg/l; 10 of these were toxin producers. Multiple antibiotic resistance (two or more antibiotics) was noted in 63 isolates. These were more common among the toxigenic strains than the non-toxigenic strains by a ratio of 2.5:1.

Activity of GAR-936 and other antimicrobial agents against North American isolates of Staphylococcus aureus

The comparative in vitro activity of GAR-936 and 12 other drugs against 602 North American isolates of methicillin-susceptible (MSSA) and methicillin-resistant (MRSA) Staphylococcus aureus was determined. The GAR-936 MICs ranged from 0.06 to 1.0 mg/l. The MIC 50s and MIC 90s were 0.12 and 0.25 mg/l for MSSA and 0.25 and 0.5 mg/l for MRSA.

Species-independent pharmacodynamics of gemifloxacin and ciprofloxacin with Haemophilus influenzae and Moraxella catarrhalis in an in vitro dynamic model

To demonstrate the antimicrobial effects of the different pharmacokinetics of gemifloxacin and ciprofloxacin, the pharmacodynamics of gemifloxacin and ciprofloxacin were studied using two clinical isolates each of Haemophilus influenzae and Moraxella catarrhalis. Monoexponentially decreasing concentrations of gemifloxacin (single dose, half-life 7.4 h) and ciprofloxacin (two 12-h doses, half-life 4 h) were simulated in an in vitro dynamic model over 8-fold ranges of the area under the curve (AUC)-to-MIC ratio: from 56 to 466 and 112–932 h, respectively. With each quinolone, log-linear relationships were established between the intensity of the antimicrobial effect ( I E) and AUC/MIC. The I E–log AUC/MIC plots were bacterial strain- and species-independent and the gemifloxacin and ciprofloxacin plots were not superimposable. To generalize the findings obtained with the studied organisms, the effects of gemifloxacin and ciprofloxacin on hypothetical strains of H. influenzae and M. catarrhalis with MICs equal to the respective MIC 90s were predicted. Based on these predictions, the AUC/MIC 90s of 320 mg gemifloxacin (800 h with H. influenzae and 400 h with M. catarrhalis) may be 31–34% more efficient than those of 2×500 mg ciprofloxacin (730 and 365 h, respectively). These data suggest greater efficacy of gemifloxacin against H. influenzae and M. catarrhalis relative to ciprofloxacin at clinically achievable AUC/MIC ratios.

In vitro susceptibility of recent clinical isolates of pneumococci to the investigational cephalosporin cefditoren

From February to June 2000, 2,597 isolates of Streptococcus pneumoniae were prospectively collected from 146 clinical laboratories across the United States (US) and tested to evaluate the in vitro activity of cefditoren, an investigational oral cephalosporin. In all, 2,492 isolates (96.0%) had a cefditoren MIC of 0.5 μg/mL or less, 74 isolates (2.8%) had an MIC of 1 μg/mL, 30 isolates (1.2%) had an MIC of 2 μg/mL, and 1 isolate (<0.1%) had an MIC of 4 μg/mL. Among the β-lactams tested, the rank order of potency (MIC 90, μg/mL) was cefditoren (0.5) > ceftriaxone (1) > amoxicillin-clavulanate (2) > cefuroxime (4) > cefprozil (8). Penicillin-resistant isolates ( n = 443; 17.1%) were inhibited by lower concentrations (MIC 90, μg/mL; MIC range,) of cefditoren (1; 0.03–4) than ceftriaxone (2; 0.25- > 2), amoxicillin-clavulanate (8; 0.5- > 8), cefuroxime (16; 2- > 16), and cefprozil (32; 2- > 32). Cefditoren MIC 90s against cefuroxime-resistant ( n = 640) and ceftriaxone-resistant ( n = 89) isolates were 1 and 2 μg/mL, respectively. All isolates with reduced susceptibility to cefditoren (MIC, 2 or 4 μg/mL; n = 31) were resistant to penicillin, cefuroxime, and ceftriaxone. The potent in vitro activity of cefditoren against a recent US collection of pneumococci as demonstrated in this study supports its continued development for oral empiric therapy in outpatients with respiratory tract infections.

In vitro activity of ABT-773, telithromycin and eight other antimicrobials against erythromycin-resistant Streptococcus pneumoniae respiratory isolates of children

The activity of the ketolide ABT-773 against 180 erythromycin-resistant Streptococcus pneumoniae obtained from children was compared with telithromycin, azithromycin, clarithromyin, roxithromycin, clindamycin, penicillin, levofloxacin and gatifloxacin. Ketolide MICs were all ≤1 mg/l, with ABT-773 being the most potent of all drugs tested. MIC 90s for macrolides and azithromycin in mefE+ isolates were 16–32 compared with >128 mg/l for ermB+ isolates. ABT-773 and telithromycin MIC 90s for mefE+ isolates were 0.125 and 0.5, compared with 0.032 and 0.016 mg/l for ermB+ isolates and 0.5 and 1 mg/l, respectively, for isolates containing both genes. Clindamycin was active against mefE+ but not ermB+ isolates. 155 isolates were resistant to penicillin. All fluoroquinolone MICs were <1 mg/l. Further studies of ketolides for treatment of paediatric S. pneumoniae infections are warranted.