Activity of cephalosporins against coagulase-negative staphylococci

Staphylococcus epidermidis has become an increasingly important pathogen as the cause of serious postoperative infection after heart and orthopedic surgery. We studied the susceptibilities of 80 blood, sternotomy, and hip isolates to vancomycin, cefazolin, cefuroxime, oxacillin, erythromycin, ciprofloxacin, and ofloxacin. The MIC90 of methicillin-susceptible isolates was 4 micrograms/ml for cefazolin and cefamandole, 8 micrograms/ml for cefuroxime, and 4 micrograms/ml for vancomycin. At 48 hr the MIC90 rose to 32 micrograms/ml for cefazolin and greater than 128 micrograms/ml for cefuroxime, and remained at 4 micrograms/ml for cefamandole and vancomycin. The MIC90 of methicillin-resistant isolates at 48 hr was 16 micrograms/ml cefamandole, 64 micrograms/ml cefazolin, greater than 128 micrograms/ml cefuroxime, and 4 micrograms/ml vancomycin. Ciprofloxacin and ofloxacin inhibited the majority of isolates at 1 microgram/ml, and vancomycin at 4 micrograms/ml. The new peptolide, daptomycin, also inhibited S. epidermidis at less than or equal to 1 microgram/ml.     

Synergy of combinations of vancomycin, gentamicin, and rifampin against methicillin-resistant, coagulase-negative staphylococci

The activity of combinations of vancomycin (2 or 10 micrograms/ml), gentamicin (0.3 micrograms/ml), and rifampin (0.03 micrograms/ml) against methicillin-resistant, coagulase-negative staphylococcal isolates was determined by the time-kill method. Combinations of rifampin with gentamicin or with vancomycin 2 micrograms/ml demonstrated enhanced killing against 13 of 17 and 13 of 25 strains, respectively. However, rifampin-resistant strains were selected with the latter combination in the remaining 12 of 25 studies.     

Activity of cephalosporins against methicillin-susceptible and methicillin-resistant, coagulase-negative staphylococci: minimal effect of beta-lactamase.

Eight cephalosporins were tested for their activity against methicillin-susceptible and methicillin-resistant, coagulase-negative staphylococci and for their resistance to beta-lactamase from methicillin-resistant, coagulase-negative staphylococci. Susceptibility testing by the agar plate method was evaluated for the effect of inoculum size and duration of incubation. Methicillin-susceptible, coagulase-negative staphylococci were highly susceptible to the cephalosporins, with cephapirin and cepahlothin showing the greatest activity, followed by cefazolin and cefamandole. Methicillin-resistant, coagulase-negative staphylococci displayed nearly total cross-resistance to the cephalosporins. Resistance increased with increasing inoculum size. Beta-Lactamases produced by methicillin-resistant, coagulase-negative staphylococci had a minimal hydrolytic effect on cepahlothin, cephapirin, cefazolin, and cefamandole and no measurable effect on cefoxitin. There was no correlation between the anti-staphylococcal activity and resistance to beta-lactamases.     

Comparative activity of CGP 31608, nafcillin, cefamandole, imipenem, and vancomycin against methicillin-susceptible and methicillin-resistant staphylococci.

The activity of CGP 31608 for 53 strains of Staphylococcus aureus and 48 strains of S. epidermidis, both methicillin susceptible and resistant, was compared with that of vancomycin, nafcillin, cefamandole, and imipenem. Microdilution MICs were determined in Mueller-Hinton broth with or without 2.5% NaCl at an inoculum of 3 x 10(5) CFU/ml with a 20-h, 37 degrees C incubation. The MICs of imipenem and CGP 31608 for methicillin-resistant strains were lower than the MICs of nafcillin or cefamandole for these strains; these differences diminished in the presence of 2.5% NaCl. Subpopulations were detected in strains of methicillin-resistant S. aureus and S. epidermidis that were resistant to all the beta-lactam antibiotics tested at 5 micrograms/ml. This resistant subpopulation produced progeny that were uniformly resistant to high concentrations of each of the beta-lactams.     

In vitro activities of vancomycin and teicoplanin against coagulase-negative staphylococci isolated from neutropenic patients.

This study reports the in vitro activities of vancomycin and teicoplanin against 185 coagulase-negative staphylococcal strains isolated from 80 neutropenic patients who received different antibiotic treatments. All strains were susceptible to vancomycin: MICs for 50 and 90% of strains tested were 2 and 4 mg/liter, respectively. Teicoplanin was less active, and MICs displayed a wider range. For only teicoplanin was there a correlation between resistance and previous treatment. At the 4- and 32-mg/liter breakpoint levels, only 20% of the strains isolated from patients without glycopeptide treatment were intermediate or resistant, whereas 49.2% of the strains from patients who had received vancomycin or teicoplanin or both were intermediate or resistant.     

Tolerance to the glycopeptides vancomycin and teicoplanin in coagulase-negative staphylococci

Tolerance to vancomycin and teicoplanin in 90 clinical isolates of coagulase-negative staphylococci (CoNS) was investigated by time-kill curve methodology. Only six strains, belonging to the Staphylococcus lugdunensis species, exhibited tolerance. The seven other S. lugdunensis strains tested displayed weak susceptibility to the bactericidal activity of glycopeptides compared to the other CoNS. These phenomena are of concern, since S. lugdunensis is recognized as one of the most pathogenic CoNS.     

In-vitro induction of resistance in coagulase-negative staphylococci to vancomycin and teicoplanin

Twenty strains of coagulase-negative staphylococci (18 strains of Staphylococcus haemolyticus and two of S. epidermidis) were serially subcultured in broth media containing subinhibitory concentrations (half the MIC) of either vancomycin or teicoplanin. The MIC of the antibiotic was again measured after five passages in antibiotic-containing broth. The organisms were then subcultured in broth containing antibiotic concentrations half of the new MIC value. The experiment was terminated after 25 passages. Only one strain developed a four-fold increase in vancomycin MIC. On the other hand, 16 strains developed four-fold MIC increases to teicoplanin.     

Interaction between ciprofloxacin and vancomycin against staphylococci

The interaction between ciprofloxacin and vancomycin against nine isolates of Staphylococcus epidermidis from cases of infective endocarditis and three strains of S. aureus was studied. Killing curves indicated the presence of antagonism in the early stages, the clinical significance of which is uncertain. No synergy was found and the combination therefore does not appear to offer any advantages over vancomycin alone for the treatment of staphylococcal infections.     

Bactericidal activities of five antibiotics during short-term exposure to coagulase-negative staphylococci.

After a 1-h exposure to concentrations used for topical prophylaxis in neurosurgical procedures, bacitracin, vancomycin, and oxacillin were bactericidal against more than 90% of 48 body fluid isolates of coagulase-negative staphylococci. More than 10% of isolates survived despite exposure for 4 h to concentrations of gentamicin and streptomycin greater than those employed for topical prophylaxis.     

The antibacterial activity of honey against coagulase-negative staphylococci

OBJECTIVES: Development of antibiotic-resistant strains of coagulase-negative staphylococci has complicated the management of infections associated with the use of invasive medical devices, and innovative treatment and prophylactic options are needed. Honey is increasingly being used to treat infected wounds, but little is known about its effectiveness against coagulase-negative staphylococci. The aim of this study was to determine the minimum active dilution of two standardized, representative honeys for 18 clinical isolates of coagulase-negative staphylococci. METHODS: An agar incorporation technique was used to determine the minimum active dilution, with dilution steps of 1% (v/v) honey [or steps of 5% (v/v) of a sugar syrup matching the osmotic effect of honey]. The plates were inoculated with 10 microL spots of cultures of the isolates. RESULTS: The honeys were inhibitory at dilutions down to 3.6 +/- 0.7% (v/v) for the pasture honey, 3.4 +/- 0.5% (v/v) for the manuka honey and 29.9 +/- 1.9% (v/v) for the sugar syrup. CONCLUSIONS: Typical honeys are about eight times more potent against coagulase-negative staphylococci than if bacterial inhibition were due to their osmolarity alone. Therefore, honey applied to skin at the insertion points of medical devices may have a role in the treatment or prevention of infections by coagulase-negative staphylococci.     

Bactericidal activity of vancomycin, daptomycin, ampicillin and aminoglycosides against vancomycin-resistant Enterococcus faecium

Daptomycin, vancomycin, ampicillin and aminoglycosides, alone or in combination, were tested for their bactericidal activity against 15 isolates of vancomycin-resistant Enterococcus faecium from immunocompromised children. The kill-kinetic studies at clinically achievable concentrations demonstrated that daptomycin alone or in combination with ampicillin had the greatest bactericidal activity.     

In vitro activity of l-ofloxacin against norfloxacin-resistant coagulase-negative staphylococci.

The in vitro activity of l-ofloxacin was determined against coagulase-negative staphylococci that were induced to norfloxacin resistance. l-Ofloxacin was the most active agent tested with an MIC90 of 4 micrograms/ml compared with greater than 128, 32, and 128 micrograms/ml for norfloxacin, ciprofloxacin, and enoxacin, respectively. Rifampin-resistant, coagulase-negative staphylococci were not cross-resistant to the quinolones tested. Among the rifampin-resistant organisms tested, l-ofloxacin was also the most active agent with an MIC90 of 0.25 micrograms/ml.     

Emergence of coagulase-negative staphylococci

ABSTRACT

Introduction: Compared to Staphylococcus aureus, coagulase-negative staphylococci (CoNS) are characterized by a lower capacity to cause acute, live-threatened infections. CoNS are, however, of ever increasing importance as pathogens causing infections in immunocompromised patients and after foreign-material implantation. Typically, antibiotics fail to cure foreign body-related infections and removal of the implanted device is inevitable.

Areas covered: This review focuses on the emergence of CoNS species, their pathogenic potential in particular due to their ability to form therapy-refractory biofilms on biotic and abiotic surfaces and evasion strategies to resist host response and antibiotic treatment. Their medical significance and proven and novel therapy strategies are discussed.

Expert opinion: CoNS contribute significantly to morbidity and socio-economic costs. The anticipated developments in modern medicine, in particular the increasing use of foreign materials and the rising numbers of immunocompromised patients, as well as the changing demographic and hospital-related factors will inevitably contribute to further emergence of CoNS infections. Increasing rates of (multi-)resistant CoNS strains will limit the therapeutic armamentarium and aggravate treatment strategies. Increased research is necessary to understand their role as resistance and virulence gene reservoir and to reduce CoNS infections by the development of innovative colonization-preventing materials and other CoNS-tailored treatment strategies.     

Synergistic action of ampicillin and nafcillin against ampicillin-resistant Haemophilus influenzae.

Six strains of ampicillin-resistant Haemophilus influenzae type b were studied in vitro for synergy between ampicillin and nafcillin. The minimal inhibitory concentrations for these strains with 10(4) colony-forming units per ml were 6.25 to 12.5 microgram of ampicillin per ml and 6.25 to 25 microgram of nafcillin per ml. Studies with these agents demonstrated synergism against all six strains of H. influenzae type b. Most strains were inhibited by 0.78 microgram of nafcillin plus 0.78 microgram of ampicillin per ml. A child with osteomyelitis caused by H. influenzae type b was successfully treated with a combination of ampicillin and nafcillin. These data suggest that further studies assessing the synergistic effect of this drug combination against H. influenzae type b are warranted.     

In-vitro activity and beta-lactamase stability of methicillin, isoxazolyl penicillins and cephalothin against coagulase-negative staphylococci

Forty-nine clinical strains of coagulase-negative staphylococci were investigated for susceptibility to methicillin, oxacillin, cloxacillin, dicloxacillin, flucloxacillin and cephalothin. The highest level of resistance was found to methicillin and the lowest to cephalothin. The resistance-level of the isoxazolyl penicillins showed a high degree of uniformity. However more strains were resistant to cloxacillin and oxacillin than to dicloxacillin and flucloxacillin. Only a weak correlation was found between beta-lactamase production, and resistance to the six antibiotics. Methicillin was the most stable. The inactivation of cephalothin differed from that of the other antibiotics.     

Effects of subinhibitory concentrations of vancomycin or cefamandole on biofilm production by coagulase-negative staphylococci.

The density of the biofilm layer produced on a plastic surface by 23 clinical isolates and 1 reference strain of slime-positive, coagulase-negative staphylococci was measured following growth in subinhibitory concentrations (sub-MICs) of cefamandole or vancomycin ranging from 2 to 0.008 micrograms/ml. All strains were susceptible to less than or equal to 2 micrograms of each agent per ml. The mean biofilm density produced by each strain was calculated from a total of eight determinations at each sub-MIC and was compared with the mean biofilm density of a drug-free control after correcting for differences in growth. The results showed that the density of the biofilm layer produced by 10 (42%) of 24 strains and 13 (54%) of 24 strains was significantly increased (P less than 0.006) at one or more sub-MICs of cefamandole or vancomycin, respectively. In contrast, the density of the biofilm produced by 9 (38%) of 24 and 2 (8%) of 24 strains was significantly reduced at one or more sub-MICs of cefamandole and vancomycin, respectively, and the biofilm density of 7 of these strains was decreased only when the sub-MIC was one-half the MIC. The biofilm density of six strains (five versus cefamandole and one versus vancomycin) was both enhanced and reduced by different sub-MICs of the same agent. None of the strains produced a detectable biofilm at or above the MIC for the strain. These data indicate that antimicrobial agents such as cefamandole or vancomycin could potentially enhance the biofilm matrix produced by certain slime-positive, coagulase-negative staphylococci on the surface of a biomedical implant if concentrations of these agents fall below the MIC for the infecting strain.     

凝固酶阴性葡萄球菌菌种鉴定与苯唑西林耐药凝固酶阴性葡萄球菌检测准确性

目的 评价凝固酶阴性葡萄球菌(CNS)菌种鉴定与苯唑西林耐药凝固酶阴件葡萄球菌(MRCNS)检测的准确性.方法 139株临床分离CNS,经ID 32 STAPH鉴定到种,用头孢西丁(FOX)、苯唑西林(OXA)纸片扩散法检测MRCNS,以Slidex MRSA detection乳胶凝集法检测青霉素结合蛋白2a(PBP2a)作为参考方法.结果 139株CNS鉴定为8个种,依次为溶血葡萄球菌、表皮葡萄球菌、人葡萄球菌、木糖葡萄球菌、腐生葡萄球菌、耳葡萄球菌、模仿葡萄球菌、沃氏葡萄球菌.FOX纸片法总的敏感度和特异度为99.0%和86.0%;OXA纸片法总的敏感度和特异度为91.7%和74.4%.影响FOX纸片法敏感度的菌种为1株表皮葡萄球菌;影响其特异度的菌种包括木糖葡萄球菌、沃氏葡萄球菌、腐生葡萄球菌;而影响OXA纸片法敏感度的菌种包括溶血葡萄球菌、人葡萄球菌、模仿葡萄球菌、耳葡萄球菌;影响其特异度的菌种包括人葡萄球菌、模仿葡萄球菌、木糖葡萄球菌、耳葡萄球菌、腐生葡萄球菌、沃氏葡萄球菌.结论 FOX纸片法检测MRCNS准确性因菌种不同有所差异,尤其应关注木糖葡萄球菌、沃氏葡萄球菌、腐生葡萄球菌的影响.建议检测MRCNS时,尽可能将CNS鉴定到种,视菌种必要时用PBP2a或mecA基因予以确认.     

In vitro interaction between rifampin and clindamycin against pathogenic coagulase-negative staphylococci.

The MICs and MBCs for 90% of strains tested (MIC90 and MBC90, respectively) of rifampin for 75 clinical isolates of pathogenic coagulase-negative staphylococci (PCNS) were 0.03 and 0.25 microgram/ml, respectively, while the MIC90 and MBC90 of clindamycin were both greater than 25 micrograms/ml. Although no synergy between rifampicin and clindamycin was found among the 15 strains studied by the checkerboard method, 6 of 12 selected strains showed synergy by the kill-curve method. No antagonism was observed by either method. All 30 strains rapidly developed resistance to rifampin in vitro, and this could be prevented by the simultaneous presence of 1.0 microgram of clindamycin per ml in the 24 methicillin-susceptible PCNS strains. The synergy between rifampin and clindamycin observed in vitro for some strains of PCNS, together with the prevention of emergence of resistance to rifampin by clindamycin, suggests that this antibiotic combination may be useful for the treatment of infections caused by methicillin-susceptible PCNS.