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In view of the alarming spread of antimicrobial resistance in the absence of new antibiotics, this study aimed at assessing the availability of potentially useful older antibiotics. A survey was performed in 38 countries among experts including hospital pharmacists, microbiologists, and infectious disease specialists in Europe, the United States, Canada, and Australia. An international expert panel selected systemic antibacterial drugs for their potential to treat infections caused by resistant bacteria or their unique value for specific criteria. Twenty-two of the 33 selected antibiotics were available in fewer than 20 of 38 countries. Economic motives were the major cause for discontinuation of marketing of these antibiotics. Fourteen of 33 antibiotics are potentially active against either resistant Gram-positive or Gram-negative bacteria. Urgent measures are then needed to ensure better availability of these antibiotics on a global scale. [ABSTRACT FROM AUTHOR]

Presents a study of patients admitted to nursing homes in the United States between November of 1990 and July of 1992 who were infected with antibiotic-resistant forms of Escherichia coli, Klebsiella pneumoniae, or both. Efforts to stop the increasing number of infections caused by ceftazidime sodium-resistant gram-negative bacteria; Number of patients in the study; Methods; Results; Conclusions.

Ceftolozane MIC(50)/MIC(90)s were 4/8 μg/ml when tested against 26 CTX-M-14-type-producing isolates and 64/>64 μg/ml against 219 CTX-M-15-type-producing isolates. The addition of 4 μg/ml tazobactam lowered the ceftolozane MIC50/MIC9(0)s to ≤ 0.25/0.5 μg/ml by broth microdilution and Etest. The zone diameters for the ceftolozane-tazobactam disks were 23 to 29 mm for 92.2% of the isolates., (Copyright © 2014, American Society for Microbiology. All Rights Reserved.)

A case-case-control study was conducted to identify independent risk factors for recovery of Escherichia coli strains producing CTX-M-type extended-spectrum β-lactamases (CTX-M E. coli) within a large Southeastern Michigan medical center. Unique cases with isolation of ESBL-producing E. coli from February 2010 through July 2011 were analyzed by PCR for blaCTX-M, blaTEM, and blaSHV genes. Patients with CTX-M E. coli were compared to patients with E. coli strains not producing CTX-M-type ESBLs (non-CTX-M E. coli) and uninfected controls. Of 575 patients with ESBL-producing E. coli, 491 (85.4%) isolates contained a CTX-M ESBL gene. A total of 319 (84.6%) patients with CTX-M E. coli (282 [74.8%] CTX-M-15 type) were compared to 58 (15.4%) non-CTX-M E. coli patients and to uninfected controls. Independent risk factors for CTX-M E. coli isolation compared to non-CTX-M E. coli included male gender, impaired consciousness, H2 blocker use, immunosuppression, and exposure to penicillins and/or trimethoprim-sulfamethoxazole. Compared to uninfected controls, independent risk factors for isolation of CTX-M E. coli included presence of a urinary catheter, previous urinary tract infection, exposure to oxyimino-cephalosporins, dependent functional status, non-home residence, and multiple comorbid conditions. Within 48 h of admission, community-acquired CTX-M E. coli (n = 51 [16%]) and non-CTX-M E coli (n = 11 [19%]) strains were isolated from patients with no recent health care contacts. CTX-M E. coli strains were more resistant to multiple antibiotics than non-CTX-M E. coli strains. CTX-M-encoding genes, especially bla(CTX-M-15) type, represented the most common ESBL determinants from ESBL-producing E. coli, the majority of which were present upon admission. Septic patients with risk factors for isolation of CTX-M E. coli should be empirically treated with appropriate agents. Regional infection control efforts and judicious antibiotic use are needed to control the spread of these organisms.

Meticillin-resistant Staphylococcus aureus (MRSA) isolates from two worldwide ceftobiprole Phase 3 clinical trials for the treatment of complicated skin and skin-structure infections were characterised by clonality, staphylococcal cassette chromosome mec (SCCmec) type and the presence of Panton-Valentine leukocidin (PVL). PVL was predominantly found in US isolates (196/231 vs. 13/110 non-US isolates). SCCmec type IV was the most common (253/329) owing to the predominance of clone USA300 in isolates from the USA (197/226). In Europe, SCCmec type III was the most prevalent (30/74). Ceftobiprole minimum inhibitory concentrations (MICs) ranged from 0.25 microg/mL to 4 microg/mL, with MICs

Background: Seven-valent pneumococcal conjugate vaccine (PCV7) provides protection against invasive pneumococcal disease that extends to unvaccinated populations, such as elderly or immunocompromised adults. PCV7 also reduces incidence of pneumococcal penicillin resistance. In this study, the potential impact of PCV7 on pneumococcal fluoroquinolone resistance was examined., Methods: U.S. levofloxacin-resistant isolates (264) from TRUST surveillance studies (1999-2004) were serotyped and quinolone resistance-determining region of parC/E and gyrA/B sequenced. Changes in prevalence of vaccine/nonvaccine serotypes during 2000-2004 and 1999-2004 were analyzed by regression analyses and chi-square trend test., Results: The introduction of PCV7 (2000-2004) did not affect fluoroquinolone resistance prevalence, but mutants with vaccine serotypes declined linearly at -6.6 +/- 0.8% per year (p = 0.003), with concomitant replacement by nonvaccine serotypes; vaccine-related serotypes (6A, 9N, 19A, and 23N) increased (p = 0.04). Differential selection between vaccine and nonvaccine serotypes occurred for mutants containing amino acid substitutions at either ParC Ser79 (p = 0.01) or both ParC Ser79 and GyrA Ser81 (p = 0.04). Among mutants with ParC Ser79 substitutions, vaccine serotypes declined linearly (p = 0.02), whereas nonvaccine serotypes increased (p = 0.04). Additionally, a vaccine-independent effect became apparent during 1999-2004, as the incidence of ParC Ser79 and Asp83 mutations declined in fluoroquinolone-resistant strains, suggesting that these substitutions conferred decreased fitness., Conclusions: PCV7 has led to extensive replacement of vaccine serotypes by nonvaccine serotypes among levofloxacin-resistant pneumococci.

The activities of ceftobiprole and other beta-lactams were examined with 30 Streptococcus pneumoniae isolates containing multiple pbp1a, pbp2b, and pbp2x mutations. The highest ceftobiprole MIC was 1 microg/ml, while the comparator MICs were 16 to 64 microg/ml. Fifty percent inhibitory concentrations for penicillin-binding protein 2x were 0.5 microg/ml (ceftobiprole) and 4 microg/ml (ceftriaxone) in a penicillin- and ceftriaxone-resistant isolate.

Objectives: Prevalence of single quinolone-resistance determining region (QRDR) mutations in Streptococcus pneumoniae was studied from nine institutions over 5 years to track the incidence of single QRDR mutations., Methods: All 1106 levofloxacin-susceptible pneumococci (MICs < or = 2.0 mg/L) identified from 1112 total isolates (99.5% susceptibility) in TRUST 3 (1999), TRUST 5 (2001) and TRUST 7 (2003) surveillance studies from the same nine hospitals in nine states were screened for QRDR mutations. Using pyrosequencing, the strains were screened for mutations corresponding to hot spots Asp-78, Ser-79 and Asp-83 in ParC; Asp-80, Ser-81 and Glu-85 in GyrA; Asp-435 in ParE and Asp-435 in GyrB. DNA sequencing of QRDRs was performed to confirm mutations., Results: No QRDR mutations were found in any of the isolates with levofloxacin MICs < or = 0.5 mg/L and no gyrA or gyrB QRDR mutations were found in any of the screened isolates (MICs < or = 2 mg/L). Four single-step QRDR mutants with the following amino acid substitutions were found: ParE Asp-435 to Asn (isolated in 1999 in Colorado); ParC Asp-83 to Asn (isolated in 2001 in Kentucky); ParC Ser-79 to Phe (isolated in 2003 in Indiana) and ParC Ser-79 to Tyr (isolated in 2003 in California). These non-clonal strains had levofloxacin MICs of 1 mg/L and were non-susceptible to ciprofloxacin (MIC 2-4 mg/L)., Conclusions: Overall prevalence of single QRDR mutations in levofloxacin-susceptible S. pneumoniae with MICs of < or = 2 mg/L was 0.4% (4/1106) and has remained <1% within nine institutions over 5 years (1999-2003).

A total of 322 erythromycin-resistant pneumococci from TRUST 3 and TRUST 4 United States surveillance studies (1999-2000) were screened for 23S rRNA, L4, and L22 gene mutations. Nineteen isolates, two with mefA, had mutations at position 2058 or 2059 in 23S rRNA. Two had a 69GTG71-to-TPS substitution in L4; one of these also contained ermA.

Objectives: To detect relatedness among 68 (0.5%) of 13 795 US clinical isolates of Streptococcus pneumoniae from the TRUST 3 (1998-1999) and TRUST 4 (1999-2000) surveillance studies that were resistant to levofloxacin (MIC > or = 8 mg/l)., Methods: All levofloxacin-resistant isolates were analysed by broth microdilution reference method for susceptibility to four fluoroquinolones, DNA sequencing of quinolone resistance determining region (QRDR) of topoisomerase IV and DNA gyrase genes, serotyping, and pulsed-field gel electrophoresis (PFGE)., Results: All levofloxacin-resistant isolates were ciprofloxacin resistant (MIC > or = 4 mg/l, FDA breakpoint) and non-susceptible to gatifloxacin (MIC > or = 2 mg/l); 62 were non-susceptible to moxifloxacin (MIC > or = 2 mg/l). Resistant isolates were in 48 (20%) of 238 institutions in 29 states. Three institutions had levofloxacin-resistant isolates in both surveillance studies. Among the resistant isolates were 17 serotypes and 48 different PFGE patterns. Fourteen isolates had PFGE patterns closely related to the Spain(23F)-1 clone; one strain had a PFGE pattern closely related to the French(9V)-3 clone. All levofloxacin-resistant isolates had two or more mutations within the QRDR of parC, parE, gyrA and gyrB., Conclusions: US levofloxacin-resistant S. pneumoniae isolates were rare and most were unrelated with minimal clonal spread, and were associated with multiple QRDR mutations with extensive cross-resistance noted among fluoroquinolones.

Levofloxacin resistance in Streptococcus pneumoniae is rare, requiring at least two mutations in the quinolone resistance-determining region (QRDR) of topoisomerase IV and DNA gyrase. The prevalence of single QRDR mutations in these genes is unknown. Of 9,438 levofloxacin-susceptible pneumococci from the TRUST 4 surveillance study (1999-2000), 528 strains (MICs of 0.5 to 2.0 microg/ml) were selected for analysis. For comparison, 214 levofloxacin-susceptible strains (MICs of 0.5 to 1 microg/ml) isolated between 1992 and 1996 were analyzed. Oligonucleotide probe assay and DNA sequencing were used to detect QRDR mutations leading to changes at Ser79 and Asp83 in ParC, Ser81 in GyrA, and Asp435 in ParE, the most frequently found substitutions among levofloxacin-resistant strains. Among the 1992 to 1996 isolates only one strain (levofloxacin MIC, 1 microg/ml) had a mutation (Ser79 to Phe in ParC). No single mutations were found among 270 TRUST 4 strains with levofloxacin MICs of 0.5 microg/ml. Among 244 strains for which levofloxacin MICs were 1 microg/ml, 15 strains (6.1%) had a parC mutation and 3 strains (1.2%) had a parE mutation. Of 14 strains for which levofloxacin MICs were 2 microg/ml, 10 strains (71%) had a parC mutation; no parE mutations were found. No gyrA mutations were detected. It was estimated that 4.5% of the 9,438 levofloxacin-susceptible TRUST 4 isolates (MICs, < or =0.06 to 2 microg/ml) had a single parC or parE QRDR mutation. Although there has been an increase in the prevalence of single-step mutants, the increase may have been overestimated due in part to differences in geographical distribution for the two sets of isolates.