Cefpodoxime for Antimicrobial Prophylaxis in Neutropenia: A Retrospective Case Series

Background

Antimicrobial prophylaxis in select neutropenic patients has reduced fever, infection rates, hospital length of stay, and hospitalization rates. Guidelines from the Infectious Diseases Society of America recommend the consideration of prophylaxis with a fluoroquinolone in patients at high risk for infection after chemotherapy. The use of fluoroquinolones has been associated with many adverse events, and there is limited evidence on alternative antimicrobial prophylaxis in patients intolerant of fluoroquinolones.

Objectives

Our study describes a single-center experience of cefpodoxime as an alternative to fluoroquinolones for antibacterial prophylaxis during neutropenia after chemotherapy and represents a retrospective evaluation of an oral cephalosporin in adult patients for this purpose.

Methods

This retrospective case series analyzed data from the electronic medical records of 41 patients having hematologic malignancies and given cefpodoxime for neutropenic prophylaxis.

Results

The rate of febrile neutropenia was 85%, with 60% culture-positive infections. Gram-positive organisms were identified in 52% of positive cultures, and gram-negative organisms represented 40% of positive cultures. Antimicrobial resistance to guideline-recommended empiric treatment regimens was not seen in breakthrough infections.

Conclusions

Cefpodoxime can be utilized for prophylaxis, without adversely affecting resistance to broad-spectrum agents, and maintains a high level of appropriateness of guideline-recommended empiric regimens. This study of cefpodoxime prophylaxis in adult patients intolerant to fluoroquinolones adds to the literature of potential alternative agents for prophylaxis in neutropenic patients.     

Structure-activity relationships between linkage style at the C-3 position and nuclear analogues of C(7)-hydroxyminoaminothiazol cephalosporins against methicillin-resistantStaphylococcus aureus

We have previously shown that hydroxy-imino-aminothiazol at the 7-position was important to the antimethicillin-resistantStaphylococcus aureus (MRSA) activity of isocephems. In this study, in order to optimize the linkage style at the C-3 position and cephem backbones, 9 compounds were prepared by combining 3 cephem backbones with 3 different linkage styles at the C-3 position. The compounds had thiopyridinum-N-carbamoylmethyl fixed as the C-3 side chain and hydroxy-imino-aminothiazol at the C-7 position on the cephem backbones. The cephem backbones tested were cephem, isocephem, and 2-oxaisocephem. The linkage styles at the C-3 position were methylene, vinyl, and propylene linkages. Clinically isolated strains of MRSA were used to determine the MICs of the 9 compounds with different combinations of cephem backbones and linkage styles at the C-3 position. The compounds with vinyl linkage styles were more active against MRSA than the compounds with other linkage styles at the C-3 position, and among the cephem backbones with vinyl linkages, the cephem backbone exhibited the strongest anti-MRSA activity. MIC₉₀s for cephem (1-S-V), isocephem (2-S-V), and 2-oxaisocephem (2-O-V) compounds were 1.56, 6.25, and 12.5 μg/mL, respectively, and the 1-S-V compound had the highest affinity to penicillin-binding protein 2′ among the 3 compounds with the vinyl-style linkage. Thus, the combination of cephem and a vinyl linkage at the C-3 position was shown to be optimal for anti-MRSA activity.     

大肠杆菌耐药质粒的头孢哌酮抗性基因克隆和定位

用鸟枪法从耐药质粒ｐＦＣ上克隆到头孢哌酮抗性基因。快速小规模制备质粒ＤＮＡ进行限制性酶切分析鉴定含重组质粒的克隆株，经多次传代，克隆株抗性表达稳定。多种限制性内切酶谱分析并构建重组质粒的物理图谱与质粒ｐＦＣ物理图谱比较，定位出头孢哌酮抗性基因在ｐＦＣ物理图谱上３２ｋｂ至４８ｋｂ区间内，其分子量约１６ｋｂ。该基因包含有ＥｃｏＲⅠ、ＳｍａⅠ、及ＰｖｕⅡ位点。     

Pharmacokinetics of ceftriaxone following intravenous administration of a 3 g dose

Summary The pharmacokinetic parameters of total (bound and unbound) and free (unbound) ceftriaxone in six healthy volunteers after intravenous injection of 39 were compared with low-dose data from a previous study. The dose-dependent behaviour of total drug was considerably more pronounced after the 3 gram dose. In contrast, total body clearance (Cl _S ^F =258 ml/min), renal clearance (Cl _R ^F =170 ml/min) and volume of distribution (V _D(β) ^F =168 l) of free (unbound) drug did not differ from the data reported earlier. There was no significant change in biological half-life (t_1/2(β)=7.8 h) or in the fraction excreted unchanged in urine (f_u=0.67).     

Novel antibacterial agents for the treatment of serious Gram-positive infections

With the continuing development of clinical drug resistance among bacteria and the advent of resistance to the recently released agents quinupristin-dalfopristin and linezolid, the need for new, effective agents to treat multi-drug-resistant Gram-positive infections remains important. This review focuses on agents presently in clinical development for the treatment of serious multidrug-resistant staphylococcal, enterococcal and pneumococcal infections, including methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci and penicillin-resistant Streptococcus pneumoniae. Agents to be discussed that affect the prokaryotic cell wall include the antimethicillin-resistant S. aureus cephalosporins BAL9141 and RWJ-54428, the glycopeptides oritavancin and dalbavancin and the lipopeptide daptomycin. Topoisomerase inhibitors include the fluoroquinolones gemifloxacin, sitafloxacin and garenoxacin. Protein synthesis inhibitors are represented by the ketolides telithromycin and cethromycin, the oxazolidinones and the glycylcycline tigecycline. Although each of these compounds has demonstrated antibacterial activity against antibiotic-resistant pathogens, their final regulatory approval will depend on an acceptable clinical safety profile.     

The use of cephalosporins for gonorrhea: the impending problem of resistance

Gonorrhea remains an important clinical and public health problem throughout the world. Gonococcal infections have historically been diagnosed by Gram stain and culture but are increasingly diagnosed through nucleic acid tests, thereby eliminating the opportunity for antimicrobial susceptibility testing. Gonococcal infections are typically treated with single-dose therapy with an agent found to cure > 95% of cases. Unfortunately, the gonococcus has repeatedly developed resistance to antimicrobials including sulfonamides, penicillin, tetracyclines and fluoroquinolones. This has now left third-generation cephalosporins as the lone class of antimicrobials recommended as first-line therapy for gonorrhea in some regions. However, resistance to oral third-generation cephalosporins has emerged and spread in Asia, Australia and elsewhere. The mechanism of this resistance seems to be associated with a mosaic penicillin binding protein (penA) in addition to other chromosomal mutations previously found to confer resistance to β-lactam antimicrobials (ponA, mtrR, penB, pilQ). Few good options exist or are in development for treating cephalosporin-resistant isolates, as most have had multidrug resistance. Preventing the spread of resistant isolates will depend on ambitious antimicrobial management programs, strengthening and expanding surveillance networks, and through effective sexually transmitted disease control and prevention.