Ceftriaxone Minimum Inhibitory Concentrations Research Articles

Detection of multidrug-resistant gonorrhoea in the Gauteng province

Two cefpodoxime-resistant Neisseria gonorrhoeae isolates were identifed with high minimum inhibitory concentrations (MIC) for oral cephalosporins. The ceftriaxone MICs for both isolates were still in the susceptible range, although raised at 0.064 mg/l. Both isolates were cultured from urethral specimens that were collected from male patients who had presented to their general practitioners with urethral discharge. Patient 1 was treated empirically with azithromycin. Patient 2, who reported having had sex with other men, was given intravenous ceftriaxone as he had recently failed two courses of oral cefxime. Both isolates were also highly resistant to ciprofoxacin, resistant to penicillin (s-lactamase negative) and resistant to tetracycline (and thus doxycycline), and exhibited decreased susceptibility to both azithromycin and gentamicin. On molecular testing, both isolates were found to have mosaic penA genes, which encode for penicillin-binding protein 2. Mosaic penA gene formation is the most common ge...

Trends in Antimicrobial Resistance of Neisseria gonorrhoeae Isolated From Korean Patients From 2000 to 2006

The recent emergence and spread of antimicrobial-resistant Neisseria gonorrhoeae has compromised treatment and control of gonorrhea. We determined recent trends in antimicrobial susceptibility of the isolates, analyzed recent use of antigonococcal agents, and investigated the relationship between fluoroquinolone nonsusceptibility and amino acid substitutions within the fluoroquinolone resistance-determining regions in Korea. The antimicrobial susceptibilities of 977 isolates of N. gonorrhoeae collected from 2000 to 2006 in Korea were determined with penicillin, ceftriaxone, spectinomycin, tetracycline, and ciprofloxacin disks. Some of the randomly selected isolates were tested by the Clinical and Laboratory Standards Institute agar dilution method, to determine subtle changes in susceptibility to the above antibiotics and cefixime. β-lactamase was detected using a cefinase disk. All of the isolates exhibited plasmid- or chromosomally mediated resistance to penicillin; however, the proportions of penicillinase-producing N. gonorrhoeae decreased rapidly from 64% in 2000 to 21% in 2006. All isolates were susceptible to third-generation cephalosporins, except for 1 isolate that was not susceptible to cefixime. The proportion of ciprofloxacin-resistant isolates increased from 26% in 2000 to 83% in 2006. Of 7 substitution types, 5 (Ser-91-Phe in Gyrase A (GyrA), Ser-87-Arg in ParC subunit of topoisomerase IV (ParC); Ser-91-Phe and Asp-95-Ala in GyrA, and Ser-87-Asn in ParC; Ser-91-Phe and Asp-95-Gly in GyrA, and Asp-86-Asn in ParC; Ser-91-Tyr in GyrA; Ser-91-Phe in GyrA, and Asp-86-Asn in ParC) were new ones not identified in our 2004 study. All isolates were susceptible to spectinomycin. About half of the patients in our current study (52.6%-58.1%, depending on the year) received spectinomycin treatment. Majorities were resistant to tetracycline, and the rate of highly tetracycline-resistant N. gonorrhoeae increased from 3% in 2000 to 9% in 2006. The incidence of penicillinase-producing N. gonorrhoeae declined significantly, but none of the isolates were susceptible to penicillin G. All isolates were susceptible to spectinomycin, in contrast majority were resistant to tetracycline. Inappropriate use of fluoroquinolone was frequent. The minimum inhibitory concentrations of ceftriaxone were within the susceptible range for all isolates, but those of cefixime were slightly higher, and it was 0.5 μg/mL (nonsusceptible) for 1 isolate.

The European gonococcal antimicrobial surveillance programme, 2009

Neisseria gonorrhoeae antimicrobial susceptibility is monitored in the European Union (EU) and the European Economic Area (EEA) by the European gonococcal antimicrobial surveillance programme (Euro-GASP). Results from 17 EU/EEA Member States in 2009 showed that 5% of isolates had decreased susceptibility to cefixime, an upward trend in the minimum inhibitory concentrations of ceftriaxone and a high prevalence of resistance to ciprofloxacin (63%)and azithromycin (13%). These results are of public health value and highlight the need for healthcare professionals to be aware of possible cefixime treatment failures. Euro-GASP is being implemented in additional EU/EEA Member States to achieve greater representativeness. In addition, Euro-GASP aims to set up a system which will allow biannual reporting of antimicrobial resistance in the EU/EEA, with a transition from centralised towards decentralised testing,and will link epidemiological data to laboratory data to enhance surveillance. The benefits of this approach include more timely detection of emerging trends in gonococcal resistance across the EU/EEA and the provision of a robust evidence base for informing national and European guidelines for therapy.

Trends in Antimicrobial Resistance in Neisseria gonorrhoeae Isolated in Canada: 2000–2009

Canada conducts surveillance of penicillin, tetracycline, erythromycin, spectinomycin, ciprofloxacin, cefixime, and ceftriaxone susceptibilities in Neisseria gonorrhoeae isolates to support development of national treatment guidelines for sexually transmitted infections. N. gonorrhoeae isolates were collected by Canadian provincial public health laboratories and included isolates from males and females ranging in age from 1 to 86 years. Minimum inhibitory concentrations (MICs) were determined by agar dilution at the National Microbiology Laboratory, Public Health Agency of Canada, and MIC interpretations were based on the criteria of the Clinical Laboratory Standards Institute. From 2000 to 2009, 40,875 isolates of N. gonorrhoeae were tested by provincial laboratories and 10,993 of these were characterized by the Public Health Agency of Canada. There was an increasing incidence of N. gonorrhoeae isolates that were chromosomally resistant to penicillin, tetracycline, and erythromycin while the plasmid-mediated resistance strains (penicillinase-producing N. gonorrhoeae, tetracycline-resistant N. gonorrhoeae, and PP/tetracycline-resistant N. gonorrhoeae strain all had a declining trend. The percentage of isolates resistant to ciprofloxacin significantly increased from 1.3% in 2000 to 25.5% in 2009. Only 0.17% of isolates tested were azithromycin resistant. Between 2000 and 2009, the modal MICs for ceftriaxone increased from 0.016 μg/mL to 0.063 μg/mL. Ciprofloxacin resistance in N. gonorrhoeae within Canada has increased to a level where quinolones are no longer the preferred drugs for the treatment of gonococcal infections and the modal MICs for the third-generation cephalosporins have increased over time. Close monitoring of antibiotic susceptibilities are required to inform treatment options.

O1-S03.01 Antimicrobial resistance to Neisseria gonorrhoea in a cohort of young men in Kisumu, Kenya: 2002–2009

BackgroundWe evaluated antimicrobial resistance in Neisseria gonorrhoeae (NG) isolated from men aged 18–24 enrolled in a randomised trial of male circumcision to prevent HIV.MethodsUrethral specimens were obtained from men with...

Multidrug resistance patterns, ceftriaxone and amoxycillin clavulanate suspectibility of E. Coli with esbl, plasmid borne ampc and other cephalosporin resistance in the waikato region, New Zealand

<h3>Aims</h3> To characterise multidrug resistance, ceftriaxone (CTXN) and amoxycillin clavulanate (AMC) minimum inhibitory concentration (MIC) distributions for <i>Escherichia coli</i> with extended spectrum beta lactamase (ESBL), plasmid borne (pAmpC) or up-regulated chromosomal AmpC (ucAmpC). <h3>Method</h3> <i>E. coli</i> isolates were screened for cephalosporin resistance and MICs determined by Vitek-II. Synergy testing used clavulanate, boronic acid and EDTA. ESR, Wellington, tested for AmpC plasmids. <h3>Results</h3> Thirty-seven isolates, mostly CTX-M ESBLs, showed clavulanate synergy and CTXN MICs were ≥8μg/mL. Among 11 isolates with pAmpC, five had MIC≤1. Eighteen isolates were negative for ESBL and pAmpC, classified as ucAmpC; 17/18 had CTXN MIC≤1. No metallobetalactamase resistance was found. Twenty-nine of the 30 <i>E. coli</i> with CTXN MIC≥64 had ESBL. AMC MICs were ≥32μg/mL for 37% of ESBL isolates and 97% of AmpC isolates. Seventy percent of ESBL isolates were resistant to cotrimoxazole, 68% to aminoglycosides, and 79% to quinolones. Isolates with pAmpC or presumed ucAmpC showed <10% resistance to other classes. <h3>Discussion</h3> CTX-M type ESBL <i>E. coli,</i> but not AmpC, are reliably detected by CLSI M100S20. Strains with CTXN MIC≥64 had ESBL and were mostly multidrug resistant but 63% showed intermediate <i>in vitro</i> susceptibility to AMC. Strains with pAmpC or presumed ucAmpC all had AMC MIC≥32 but rarely multi-resistance.

Molecular and Structural Analysis of Mosaic Variants of Penicillin-Binding Protein 2 Conferring Decreased Susceptibility to Expanded-Spectrum Cephalosporins in Neisseria gonorrhoeae: Role of Epistatic Mutations

Mutations in penicillin-binding protein 2 (PBP 2) encoded by mosaic penA alleles are crucial for intermediate resistance to the expanded-spectrum cephalosporins ceftriaxone and cefixime in Neisseria gonorrhoeae. Three of the ∼60 mutations present in mosaic alleles of penA, G545S, I312M, and V316T, have been reported to be responsible for increased resistance, especially to cefixime [Takahata, S., et al. (2006) Antimicrob. Agents Chemother. 50, 3638-3645]. However, we observed that the minimum inhibitory concentrations (MICs) of penicillin, ceftriaxone, and cefixime for a wild-type strain (FA19) containing a penA gene with these three mutations increased only 1.5-, 1.5-, and 3.5-fold, respectively. In contrast, when these three mutations in a mosaic penA allele (penA35) were reverted back to the wild type and the gene was transformed into FA19, the MICs of the three antibiotics were reduced to near wild-type levels. Thus, these three mutations display epistasis, in that their capacity to increase resistance to β-lactam antibiotics is dependent on the presence of other mutations in the mosaic alleles. We also identified an additional mutation, N512Y, that contributes to the decreased susceptibility to expanded-spectrum cephalosporins. Finally, we investigated the effects of a mutation (A501V) currently found only in nonmosaic penA alleles on decreased susceptibility to ceftriaxone and cefixime, with the expectation that this mutation may arise in mosaic alleles. Transfer of the mosaic penA35 allele containing an A501V mutation to FA6140, a chromosomally mediated penicillin-resistant isolate, increased the MICs of ceftriaxone (0.4 μg/mL) and cefixime (1.2 μg/mL) to levels above their respective break points. The proposed structural mechanisms of these mutations are discussed in light of the recently published structure of PBP 2.

SalmonellaIsolates with Decreased Susceptibility to Extended-Spectrum Cephalosporins in the United States

We describe the antimicrobial susceptibility to extended-spectrum cephalosporins in non-Typhi Salmonella (NTS) isolated from humans in the United States and explore resistance mechanisms for isolates displaying decreased susceptibility to ceftriaxone or ceftiofur. We further explore the concordance between the newly revised Clinical and Laboratory Standards Institute (CLSI) breakpoints for ceftriaxone and the presence of a β-lactamase. In 2005 and 2006, public health laboratories in all U.S. state health departments forwarded every 20th NTS isolate from humans to Centers for Disease Control and Prevention as part of the National Antimicrobial Resistance Monitoring System (NARMS) for enteric bacteria. Minimum inhibitory concentrations (MICs) were determined by broth microdilution. Isolates displaying decreased susceptibility (MIC ≥ 2 mg/L) to ceftriaxone or ceftiofur were included in the study. The presence of β-lactamase genes was investigated by polymerase chain reaction amplification and sequencing, targeting six different genes (bla(TEM), bla(OXA), bla(SHV), bla(CTX-M), bla(PSE), and bla(CMY)). Plasmid location of bla(CMY) was confirmed by transforming plasmids into Escherichia coli. Among the 4236 isolates of NTS submitted to NARMS in 2005 and 2006, 175 (4.1%) displayed decreased susceptibility to either ceftriaxone or ceftiofur. By polymerase chain reaction screening, one or more β-lactamase genes could be detected in 139 (80.8%) isolates. The most prevalent resistance mechanism detected was the AmpC β-lactamase gene bla(CMY.) Other β-lactamase genes detected included 11 bla(TEM-1), 3 bla(PSE-1), 2 bla(OXA-1), and 1 bla(CTX-M-15). The ceftriaxone MIC values for the bla(CMY)-containing isolates ranged from 4 to 64 mg/L; all bla(CMY)-bearing isolates were classified as ceftriaxone resistant according to current CLSI guidelines. Among NTS isolates submitted to NARMS in 2005 and 2006, cephamycinase β-lactamases are the predominant cause of decreased susceptibility to ceftriaxone. The fact that all bla(CMY)-containing isolates were classified as resistant to ceftriaxone (MIC ≥ 4 mg/L) supports the newly revised CLSI breakpoints for cephalosporins and Enterobacteriaceae.

Antimicrobial susceptibility of Neisseria gonorrhoeae isolates determined by the agar dilution, disk diffusion and Etest methods: comparison of results using GC agar and chocolate agar

Although the use of GC agar for determining Neisseria gonorrhoeae antimicrobial susceptibilities is suggested by Clinical and Laboratory Standard Institute (CLSI) guidelines, chocolate agar is still used in some regions owing to its low cost and availability. To determine the differences in susceptibilities determined using GC and chocolate agars, 163 non-duplicate N. gonorrhoeae isolates were tested. Minimum inhibitory concentrations (MICs) and percent susceptibilities determined using the GC agar dilution method, respectively, were as follows: ceftriaxone, 0.004–0.125 mg/L, 100%; cefixime, 0.002 mg/L to >32 mg/L, 98.2%; and ciprofloxacin, 0.002 mg/L to >32 mg/L, 3.1%. Comparison of ceftriaxone MICs determined by the Etest using GC agar and chocolate agar showed that use of GC agar tended to result in lower MICs than GC agar dilution, whilst use of chocolate agar tended to result in higher MICs (concordance, 55.8% and 82.8%, respectively). Disk inhibition zones obtained using GC agar and chocolate agar (and their correlation coefficients) were, respectively: ceftriaxone, 35–55 mm and 25–50 mm (0.46); ciprofloxacin, 6–55 mm and 6–43 mm (0.84); and penicillin, 6–47 mm and 6–50 mm (0.93). Use of chocolate agar with the disk diffusion method for ceftriaxone was associated with a 5.5% false resistance rate. In summary, compared with GC agar, susceptibility testing using chocolate agar tends to yield higher MICs with the Etest and smaller disk inhibition zones with disk diffusion methods. Clinical microbiology laboratories should strictly adhere to CLSI recommendations by using GC agar instead of chocolate agar when performing susceptibility testing for N. gonorrhoeae.

A simple broth-disk method to determine the minimum inhibitory concentration of ceftriaxone on Salmonella enterica serovar typhi and paratyphi

Resistance to fluoroquinolones and cephalosporins is a major problem with Salmonella enterica serovar Typhi and Paratyphi. An accurate determination of antibiotic susceptibility requires tests for minimum inhibitory concentration (MIC) of antibiotics. We describe a simple broth-disk method to determine the MIC of ceftriaxone on S. typhi and S. paratyphi. Sixteen strains of S. typhi and two strains each of S. paratyphi A and S. paratyphi B were used in the study. The MIC of ceftriaxone was determined using the simple broth-disk method and the conventional broth macrodilution method and the results were compared. All salmonella strains were susceptible to ceftriaxone. The results of the broth-disk and the conventional broth macrodilution method were similar. The broth-disk method is a simple, reliable and cost-effective method to determine the MIC of ceftriaxone on S. typhi and S. paratyphi A.

Effect of the Inoculum Size on Carbapenem Susceptibilities of β-Lactamase-Negative, Ampicillin-Resistant Haemophilus influenzae

A higher inoculum size of beta-lactamase-positive Haemophilus influenzae is reported to increase minimum inhibitory concentrations (MICs) for beta-lactams. However, the effect of inoculum size of beta-lactamase-negative, ampicillin-resistant H. influenzae (BLNAR) on MICs for carbapenems has not been investigated. This study evaluated the effect of inoculum size on MICs for carbapenems and other beta-lactams in nine clinical isolates of BLNAR. The MICs were determined by both the standard method described by the Clinical and Laboratory Standards Institute (final inoculum size of 5 x 10(5) colony-forming units [CFU]/ml) and a modified method (final inoculum size of 5 x 10(6) CFU/ml) using viable cell counts. The findings showed that the higher inoculum size increased MICs for imipenem, meropenem, panipenem, biapenem, ampicillin, ceftazidime, and ceftriaxone. The inoculum effect (4 log(2) dilution or a greater increase in the MIC) with imipenem, meropenem, panipenem, and biapenem was found in three, five, two, and two isolates, respectively. The magnitude of the inoculum effect for panipenem significantly increased with the levels of MICs, but correlation between them for the others was not statistically significant. The mutations of penicillin-binding protein genes had little relevance to the reduced susceptibility to carbapenems or to the magnitude of the inoculum effect. These results suggest that MIC determination using turbidity can produce interpretive errors in the antimicrobial susceptibility testing of BLNAR for carbapenems because of their inoculum effect. Thus, accurate adjustment of inoculum size, such as viable cell count, is helpful for confirming the true MICs when the isolates are interpreted as "resistant" by turbidity-based MIC determination.

Escalation in the relative prevalence of ciprofloxacin-resistant gonorrhoea among men with urethral discharge in two South African cities: association with HIV seropositivity

Objectives:The objectives of this study were to assess the prevalence of ciprofloxacin-resistant gonorrhoea in two South African cities and to investigate the association between the isolation of ciprofloxacin-resistant Neisseria gonorrhoeae...

Characterization of methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci and extended-spectrum beta-lactamase-producing Escherichia coli in intensive care units in Canada: Results of the Canadian National Intensive Care Unit (CAN-ICU) study (2005-2006).

Methicillin-resistant Staphylococcus aureus (MRSA), extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and vancomycin-resistant enterococci (VRE) are important hospital pathogens in Canada and worldwide. To genotypically and phenotypically characterize the isolates of MRSA, VRE and ESBL-producing E coli collected from patients in Canadian intensive care units (ICUs) in 2005 and 2006. Between September 1, 2005, and June 30, 2006, 19 medical centres participating in the Canadian National Intensive Care Unit (CAN-ICU) study collected 4133 unique patient isolates associated with infections in ICUs. Isolates of MRSA underwent mecA polymerase chain reaction (PCR) and Panton-Valentine leukocidin analysis; they were typed using pulsed-field gel electrophoresis. All isolates of E coli with ceftriaxone minimum inhibitory concentrations greater than or equal to 1 mug/mL were tested for the presence of an ESBL using the Clinical Laboratory Standards Institute double-disk diffusion method. Subsequently, PCR and sequence analysis were used to identify bla(SHV), bla(TEM) and bla(CTX-M). Isolates of VRE were tested for the presence of vanA and vanB genes by PCR. Of the 4133 ICU isolates collected, MRSA accounted for 4.7% (193 of 4133) of all isolates. MRSA represented 21.9% (193 of 880) of all S aureus collected during the study; 90.7% were health care-associated MRSA strains and 9.3% were community-associated MRSA strains. Resistance rates for the isolates of MRSA were 91.8% to levofloxacin, 89.9% to clarithromycin, 76.1% to clindamycin and 11.7% to trimethoprim-sulfamethoxazole; no isolates were resistant to vancomycin, linezolid, tigecycline or daptomycin. ESBL-producing E coli accounted for 0.4% (18 of 4133) of all isolates and 3.7% (18 of 493) of E coli isolates. All 18 ESBL-producing E coli were PCR-positive for CTX-M, with bla(CTX-M-15) occurring in 72% (13 of 18) of isolates. All ESBL-producing E coli displayed a multidrug-resistant phenotype (resistant to third-generation cephalosporins and one or more other classes of antimicrobials), with 77.8% of isolates resistant to ciprofloxacin, 55.6% resistant to trimethoprim-sulfamethoxazole, 27.8% resistant to gentamicin and 26.3% resistant to doxycycline; all isolates were susceptible to ertapenem, meropenem and tigecycline. VRE accounted for 0.4% (17 of 4133) of all isolates and 6.7% (17 of 255) of enterococci isolates; 88.2% of VRE had the vanA genotype. Isolated VRE that were tested were uniformly susceptible to linezolid, tigecycline and daptomycin. MRSA isolated in Canadian ICUs in 2005 and 2006 was predominately health care-associated (90.7%), ESBL-producing E coli were all CTX-M producers (72% bla(CTX-M-15)) and VRE primarily harboured a vanA genotype (88.2%). MRSA, ESBL-producing E coli and VRE were frequently multidrug resistant.

Antimicrobial susceptibility and genetic characteristics ofHaemophilus influenzaeisolated from patients with respiratory tract infections between 1987 and 2000, including β-lactamase-negative ampicillin-resistant strains

The minimum inhibitory concentration (MIC) of five antibiotics and the presence of resistance genes was determined in 163 Haemophilus influenzae isolates collected over 13 years (1987-2000) in four two-yearly sampling periods from patients with respiratory tract infections. The prevalence of beta-lactamase-negative ampicillin-susceptible strains was approximately 80% over the sampling period although fewer strains (65.9%) were recovered in the period 1995-1997. TEM-1 type beta-lactamase-producing strains were less frequent starting at 15.6% and declining to 2.2% in the final sampling period. Low-beta-lactamase-negative ampicillin-resistant (BLNAR) strains were uncommon in 1987-1989 (2.2%), peaked to 19.5% in 1995-1997, but fell back to 11.1% by 2000. Fully BLNAR strains were not detected until the last sampling period (6.7%). The MICs of ampicillin, levofloxacin, cefditoren and ceftriaxone remained stable but there was an eight-fold increase in the MIC of cefdinir over the sampling period. Pulsed-field gel electrophoresis of DNA digests showed that three representative BLNAR strains were genetically distinct and 11 DNA profiles were identified among 17 low-BLNAR strains. These data suggest that the number of genetically altered BLNAR and low-BLNAR strains are increasing in Japan.

Use of Local Community Hospital Data for Surveillance of Antimicrobial Resistance

We sought to determine whether antimicrobial susceptibility data from a nonteaching community hospital could be used to detect statistically significant local increases in resistance among Streptococcus pneumoniae over a 5-year period. Minimum inhibitory concentrations (MICs) of penicillin and ceftriaxone from 1997-1998 were compared with those from 2000-2001. MICs of penicillin and ceftriaxone for organisms collected in a nonteaching community hospital in central Illinois were used for analysis. The hospital has 224 beds and a catchment area of approximately 40 miles. There were significant increases in MICs of penicillin and ceftriaxone between 1997-1998 and 2000-2001. The MIC of penicillin increased from 0.042 to 0.121 microg/mL (P = .001; 95% confidence interval, -1.713 to -0.388), and the MIC of ceftriaxone increased from 0.028 to 0.071 microg/mL (P = .005; 95% confidence interval, -1.353 to -0.188). There were no significant changes in the percentage of S. pneumoniae isolates that were resistant, intermediate, or susceptible to penicillin and ceftriaxone. MIC data from a community hospital can be used to detect local increases in the rate of resistance before antibiogram data show significant changes. This information is important for demonstrating to physicians the need to review local antibiotic use in the attempt to slow the development of resistant organisms in the community.

Explaining the Poor Bacteriologic Eradication Rate of Single-Dose Ceftriaxone in Group A Streptococcal Tonsillopharyngitis: A Reverse Engineering Solution Using Pharmacodynamic Modeling

To explore pharmacokinetic factors underlying the poor bacteriologic eradication rate with a single 500-mg dose of ceftriaxone for streptococcal tonsillopharyngitis and to identify the minimum ceftriaxone dose required for effective treatment. Population modeling techniques were applied to pharmacokinetic data derived from paired plasma and tonsil samples from 153 children to assess the contribution of pharmacokinetic variability to patients' responses to ceftriaxone. In addition, a Monte Carlo simulation was performed to determine (1) the amount of time that free ceftriaxone concentrations must exceed the minimum inhibitory concentration (MIC) of group A Streptococcus to achieve bacteriologic eradication and (2) the ceftriaxone dose required to maintain free drug concentrations above the target MIC for the requisite amount of time. Ceftriaxone MICs for group A Streptococcus were obtained from a previous trial, in which all MICs (n = 115) were < or = 0.064 mg/L; 33.9% were susceptible at < or = 0.016 mg/L, 66.4% were susceptible at 0.032 mg/L, and 1.7% were susceptible at 0.064 mg/L. Mean population pharmacokinetic parameters and their variances reflected substantial variability of clearance and half-life in the target population. Tonsillar ceftriaxone protein binding was 89.1%. The proportions of 1000 simulated patients with free ceftriaxone concentrations that exceeded MICs of 0.016 mg/L, 0.032 mg/L, and 0.064 mg/L at 24 hours were 71.7%, 65.4%, and 57.2%, respectively, and at 48 hours were 41.8%, 35.8%, and 28.6%, respectively. The amount of time that free ceftriaxone concentrations need to exceed MIC to achieve bacteriologic success was estimated to be 36 hours. Using this time criterion, two 500-mg doses of ceftriaxone separated by 18 hours should achieve a bacteriologic cure rate of approximately 95%. Pharmacokinetic variability and high ceftriaxone tonsillar protein binding explain the high microbiologic failure rate for a single 500-mg dose of ceftriaxone in group A streptococcal tonsillopharyngitis. Monte Carlo simulation suggests that a second dose administered 18 hours after the first will be required to achieve an acceptable bacteriologic cure rate.

Factors Associated with Relative Rates of Antimicrobial Resistance amongStreptococcus pneumoniaein the United States: Results from the TRUST Surveillance Program (1998–2002)

To identify factors associated with antimicrobial resistance, data were analyzed from 27,828 isolates of Streptococcus pneumoniae submitted to the Tracking Resistance in the United States Today (TRUST) surveillance program during 4 consecutive respiratory seasons. From the 1998-1999 season to the 2001-2002 season, the prevalence of azithromycin resistance increased by 4.8% to 27.5%, the prevalence of penicillin resistance increased by 3.7% to 18.4%, the prevalence of ceftriaxone resistance increased by 0.5% to 1.7%, and the prevalence of levofloxacin resistance increased by 0.3% to 0.9%. Isolates recovered from patients <18 years of age and lower respiratory tract specimens had elevated rates of penicillin, azithromycin, and trimethoprim-sulfamethoxazole resistance (P<.00001); penicillin resistance correlated with coresistance to trimethoprim-sulfamethoxazole (87.3%), azithromycin (76.3%), ceftriaxone (9.1%), and levofloxacin (1.3%) (P<.00001). Only 62 (0.2%) of 27,828 isolates were concurrently resistant to penicillin and levofloxacin. Minimum inhibitory concentrations (MICs) of penicillin correlated strongly with MICs of ceftriaxone (R2=0.90), trimethoprim-sulfamethoxazole (R2=0.53), and azithromycin (R2=0.41). Patient age, specimen source, and penicillin resistance were factors associated with antimicrobial resistance, particularly for nonfluoroquinolone antimicrobial agents.

Emergence of domestically acquired ceftriaxone-resistant Salmonella infections associated with AmpC beta-lactamase.

Ceftriaxone, an expanded-spectrum cephalosporin, is an antimicrobial agent commonly used to treat severe Salmonella infections, especially in children. Ceftriaxone-resistant Salmonella infections have recently been reported in the United States, but the extent of the problem is unknown. To summarize national surveillance data for ceftriaxone-resistant Salmonella infections in the United States and to describe mechanisms of resistance. Case series and laboratory evaluation of human isolates submitted to the Centers for Disease Control and Prevention from 17 state and community health departments participating in the National Antimicrobial Resistance Monitoring System (NARMS) for enteric bacteria between 1996 and 1998. Patients with ceftriaxone-resistant Salmonella infections between 1996 and 1998 were interviewed and isolates with decreased ceftriaxone susceptibility were further characterized. Exposures and illness outcomes, mechanisms of resistance. The prevalence of ceftriaxone-resistant Salmonella was 0.1% (1 of 1326) in 1996, 0.4% (5 of 1301) in 1997, and 0.5% (7 of 1466) in 1998. Ten (77%) of the 13 patients with ceftriaxone-resistant infections were aged 18 years or younger. The patients lived in 8 states (California, Colorado, Kansas, Massachusetts, Maryland, Minnesota, New York, and Oregon). Nine (82%) of 11 patients interviewed did not take antimicrobial agents and 10 (91%) did not travel outside the United States before illness onset. Twelve of the 15 Salmonella isolates with ceftriaxone minimum inhibitory concentrations of 16 microg/mL or higher were serotype Typhimurium but these isolates had different pulsed-field gel electrophoresis patterns. Thirteen of these 15 isolates collected between 1996 and 1998 were positive for a 631-base pair polymerase chain reaction product obtained by using primers specific for the ampC gene of Citrobacter freundii. Domestically acquired ceftriaxone-resistant Salmonella has emerged in the United States. Most ceftriaxone-resistant Salmonella isolates had similar AmpC plasmid-mediated resistance.

Prediction of bacterial susceptibility to cefpodoxime by using the ceftriaxone minimum inhibitory concentration result

The cross-resistance or cross-susceptibility of cefpodoxime and ceftriaxone for 3700 strains of Enterobacteriaceae, oxacillin-susceptible staphylococci, Streptococcus spp., Haemophilus influenzae, Moraxella catarrhalis, and Neisseria gonorrhoeae was evaluated. With the exception of tests with Enterobacter spp. and Morganella morganii, the ceftriaxone minimum inhibitory concentration (MIC) result interpretive criteria predicted bacterial susceptibility (or resistance) to cefpodoxime with an acceptable rate of serious interpretive errors (1.5%) and an absolute categorical agreement >92%. By using cefpodoxime interpretive criteria for ceftriaxone MICs, the interpretive errors for testing enteric bacilli were reduced from 2.1% to 1.5%.

One-Shot Treatment of Uncomplicated Gonorrhoea with Third-Generation Cephalosporins with Differing Serum Half-Life

The highest minimum inhibitory concentrations of ceftriaxone and cefotaxime in 89 analysed Neisseria gonorrhoeae isolates amounted to 0.008 and 0.031 micrograms/ml, respectively. In a randomized controlled trial the single intramuscular injection of ceftriaxone 250 mg and cefotaxime 500 mg cured bacteriologically 35 out of 35, and 29 out of 30 patients, respectively, with uncomplicated gonorrhoea. Facing the different phenotypes of the isolates grown before and after therapy in the case of the non-cured patient within the cefotaxime treatment group, reinfection rather than failure has to be presumed. Postgonococcal urethritis occurred about as often in both groups, the percentage amounting to 24.2 and 28.6%, respectively. If side effects were noted at all, they were considered minor: 4 patients belonging to the first and 3 belonging to the second treatment group complained temporarily about pain at the injection site. Due to the data presented here, ceftriaxone and cefotaxime appear equally effective and safe when used in the dose generally preferred, irrespective of differences in in vitro activity and pharmacokinetic behaviour.