Failure of cephaloridine in a case of staphylococcal endocarditis.

Burgess, H. A.; Evans, R. J.

doi:10.1136/bmj.2.5524.1244

Cited by 25 publications

(5 citation statements)

References 5 publications

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“…They stated that the number of organisms in the diseased bone (approximately 105 to 106 CFU/ml) was large enough, at least theoretically, for the production of enough ,B-lactamase to inactivate cephaloridine. Burgess and Evans reported that apparently adequate doses of cephaloridine did not cure staphylococcal endocarditis, presumably because of the production of staphylococcal ,B-lactamase (6). In general, the PRPs and cephalothin can be used successfully to treat infections caused by 1-lactamase-producing S. aureus, even though the ,B-lactamase can be shown in vitro to slowly inactivate the drug.…”

Section: Resultsmentioning

confidence: 99%

The role of beta-lactamase in staphylococcal resistance to penicillinase-resistant penicillins and cephalosporins

McDougal¹,

Thornsberry²

1986

J Clin Microbiol

300

104

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We showed that most Staphylococcus aureus strains that have borderline or intermediate susceptibility to the penicillinase-resistant penicillins (PRPs) react this way because of the activity of their jI-lactamase on these antimicrobial agents. These strains produced large amounts of staphylococcal ,I-lactamase that rapidly hydrolyzed penicillin and partially hydrolyzed the PRPs. Susceptibility to hydrolysis was penicillin > oxacillin > cephalothin > methicillin. The borderline results and the hydrolysis could be prevented by the j-lactamase inhibitors clavulanic acid and sulbactam. For intrinsically methicillin-resistant (heteroresistant) S. aureus, the inhibitors reduced the penicillin MICs, but the strains remained resistant to all the I-lactam antimicrobial agents, including penicillin. We conclude that the borderline in vitro susceptibility or resistance to PRPs in most of these S. aureus strains is mediated by j-lactamase and they are not heteroresistant or intrinsically resistant. We do not know whether this in vitro resistance is expressed clinically. We have received several problem isolates of Staphylococcus aureus from different areas of the United States that yielded borderline-susceptible (24-h incubation) or intermediate (48-h incubation) results for oxacillin and methicillin by the usual testing methods (25, 26). The MICs for these strains were 4 ,ug/ml (methicillin), 2 ,ug/ml (oxacillin), and 2 ,ug/ml (cephalothin) after 24 h of incubation at 35°C when tested by the broth microdilution method with cationsupplemented Mueller-Hinton broth (CSMHB) and 2% NaCl (36). After incubation for 48 h, the MICs generally increased 1 dilution. With disk diffusion tests using a 1-,ug oxacillin disk, zone sizes ranged from 6 to 13 mm. These isolates of borderline-susceptible S. aureus produced large amounts of staphylococcal P-lactamase as shown by their high penicillin MICs and immediate strong positive results when tested with nitrocefin. In previous studies, we showed that staphylococcal ,-lactamase affects the zone sizes attained with the disk diffusion method, in that S. aureus strains that were P-lactamase positive yielded smaller zones of inhibition than strains that were P-lactamase negative but had the same MIC (24). These observations raised the question of whether these borderline-susceptible S. aureus isolates were truly heteroresistant (often called intrinsically resistant) or whether the apparent in vitro resistance in the MIC test was caused by P-lactamase. Previous reports have shown that staphylococcal ,B-lactamase, when present in sufficient quantities for a sufficient duration, slowly hydrolyzes the penicillinase-resistant penicillins (PRPs) and cephalosporins (1, 4, 8, 9, 17-22, 28, 34). In view of this finding, we initiated studies to estimate the amount of P-lactamase produced by each S. aureus isolate by using penicillin MICs and nitrocefin test results. We also studied the effect of two P-lactamase inhibitors (clavulanic acid and sulbactam) on the MICs of penicillin, oxacillin, cephalothin, ...

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Section: Resultsmentioning

confidence: 99%

The role of beta-lactamase in staphylococcal resistance to penicillinase-resistant penicillins and cephalosporins

McDougal¹,

Thornsberry²

1986

J Clin Microbiol

300

104

View full text Add to dashboard Cite

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“…However, early on, it was noted that cephaloridine activity was impaired against penicillin-resistant S. aureus strains when tested at high inoculum [7, 8]. A case of failure of cephaloridine in the treatment of MSSA endocarditis supported the initial concerns of cephalosporin treatment in deep-seated infections caused by MSSA [9]. …”

mentioning

confidence: 99%

The Cefazolin Inoculum Effect Is Associated With Increased Mortality in Methicillin-Susceptible Staphylococcus aureus Bacteremia

Miller

Seas

Carvajal

et al. 2018

Open Forum Infectious Diseases

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BackgroundRecent studies have favored the use of cefazolin over nafcillin for the treatment of methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia. The clinical influence of the cefazolin inoculum effect (CzIE) in the effectiveness of cephalosporins for severe MSSA infections has not been evaluated.MethodsWe prospectively included patients from 3 Argentinian hospitals with S. aureus bacteremia. Cefazolin minimum inhibitory concentrations (MICs) were determined at standard (105 colony-forming units [CFU]/mL) and high (107 CFU/mL) inoculum. The CzIE was defined as an increase of MIC to ≥16 µg/mL when tested at high inoculum. Whole-genome sequencing was performed in all isolates.ResultsA total of 77 patients, contributing 89 MSSA isolates, were included in the study; 42 patients (54.5%) had isolates with the CzIE. In univariate analysis, patients with MSSA exhibiting the CzIE had increased 30-day mortality (P = .034) and were more likely to have catheter-associated or unknown source of bacteremia (P = .033) compared with patients infected with MSSA isolates without the CzIE. No statistically significant difference between the groups was observed in age, clinical illness severity, place of acquisition (community vs hospital), or presence of endocarditis. The CzIE remained associated with increased 30-day mortality in multivariate analysis (risk ratio, 2.65; 95% confidence interval, 1.10–6.42; P = .03). MSSA genomes displayed a high degree of heterogeneity, and the CzIE was not associated with a specific lineage.ConclusionsIn patients with MSSA bacteremia where cephalosporins are used as firstline therapy, the CzIE was associated with increased 30-day mortality. Clinicians should be cautious when using cefazolin as firstline therapy for these infections.

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“…However, these antibiotics are only relatively resistant to the action of staphylococcal penicillinase and compounds such as flucloxacillin can be destroyed to a considerable extent by staphylococcal penicillinase (Lacey and Lewis, 1976) and it would now seem unwise to rely on flucloxacillin alone in treating osteomyelitis. A similar argument applies to the cephalosporins where some, such as cephaloridine, are highly inactivated by the penicillinase and there is experimental and therapeutic evidence that supports this (Burgess and Evans, 1966). Other agents that have been used in the treatment of osteomyelitis include fusidic acid, erythromycin and lincomycin.…”

Section: Osteomyelitismentioning

confidence: 94%

A new look at erythromycin

Lacey

1977

Postgraduate Medical Journal

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Summary This article reviews the current place of erythromycin in antibiotic therapy. Overall, erythromycin is thought to be underused because: (1) the fear of resistance has been exaggerated; (2) significant toxicity has been associated with only one derivative (the estolate); (3) newer antibiotics have very rarely been demonstrated to be superior to erythromycin. Erythromycin has an important place in treating acute upper and lower respiratory tract infections, acute otitis media, sinusitis, skin and soft tissue, osteomyelitis, prostatitis, infections due to Mycoplasma spp. and Chlamydia organisms, and infections due to anaerobes.

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Failure of cephaloridine in a case of staphylococcal endocarditis.

Cited by 25 publications

References 5 publications

The role of beta-lactamase in staphylococcal resistance to penicillinase-resistant penicillins and cephalosporins

The role of beta-lactamase in staphylococcal resistance to penicillinase-resistant penicillins and cephalosporins

The Cefazolin Inoculum Effect Is Associated With Increased Mortality in Methicillin-Susceptible Staphylococcus aureus Bacteremia

A new look at erythromycin

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