-Lactam Enhancement of Aminoglycoside Activity under Conditions of Reduced pH and Oxygen Tension That May Exist in Infected Tissues

Bryant, Richard E.; Fox, Kaye E.; Oh, George; Morthland, Virginia H.

doi:10.1093/infdis/165.4.676

Cited by 40 publications

(28 citation statements)

References 22 publications

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“…Ciprofloxacin plus rifampin is more effective in an E. coli model [165] and significantly more effective in an S. aureus model [166], as compared with the effectiveness of ciprofloxacin alone. The combination of cefotaxime and amikacin is significantly more effective than either agent alone in an E. coli model [159].…”

Section: Discussionmentioning

confidence: 94%

“…Although it is likely that antimicrobial concentrations may exceed the MICs for the involved pathogens, there are multiple reasons why antimicrobials may fail to eradicate organisms in an abscess milieu [159]. The low pH, ionic composition, and low oxygen concentration may be inhibitory to antimicrobial activity.…”

Section: Discussionmentioning

confidence: 99%

“…Although the number of cases is small, this suggests that aminoglycoside activity in an abscess environment may be suboptimal [1,159].…”

Section: Discussionmentioning

confidence: 99%

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Outcome of Medical Treatment of Bacterial Abscesses Without Therapeutic Drainage: Review of Cases Reported in the Literature

Bamberger

1996

Clinical Infectious Diseases

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The usual treatment of bacterial abscesses, except lung or tubo-ovarian abscesses, includes therapeutic drainage. Increasing evidence suggests that some abscesses respond to antimicrobial therapy without drainage. To study this issue, a MEDLINE search of the literature was performed for cases of bacterial abscess in which treatment without definitive drainage was attempted. Four hundred sixty-five cases were identified. The most commonly involved organs were the liver, brain, and kidney. The success rate of antimicrobial therapy was 85.9%. Factors that predicted a less favorable outcome were abscess diameter of~5 em (odds ratio [OR] = 37.7; P = .0003), involvement of~1 organism (OR = 5.2; P = .014), presence of gram-negative bacilli (OR = 3.4; P = .022), length of therapy of <4 weeks (OR = 49.1; P < .0001), and use of an aminoglycoside as the only active agent (OR = 11.8; P = .008). Many bacterial abscesses can be treated without drainage; abscess size, the organisms involved, and therapy utilized may influence outcome.Bacterial abscesses usually require drainage for cure. Reasons postulated for the ineffectiveness of antibiotics in the treatment of abscesses include the presence of stationary-phase organisms, low pH, high protein content, the large number of bacteria within abscesses, ionic composition, low oxygen tension, sequestration of bacteria within leukocytes, low abscess zinc concentrations, and the presence of antimicrobial agent-deactivating enzymes [1]. Antimicrobial therapy is generally ineffective in experimental models of suppurative infections when initiation of therapy is delayed for ;?:24 hours [2].See the editorial response by Lerner on pages 604-7.It has long been recognized that lung abscesses respond to prolonged courses of antimicrobials without formal surgical drainage. Since many lung abscesses have air-fluid levels that were observed radiographically, suggesting bronchial communication, it is likely that lung abscesses spontaneously drain via the bronchial tree. It has also been well recognized that most abscesses of the tubo-ovarian region-especially those <8 em in diameter-respond to antimicrobial therapy without the need for surgical drainage [3], perhaps again because spontaneous drainage occurs via the fallopian tubes. Since the 1970s there has been an increasing number of reports of other abscesses, especially those involving the brain, liver, and kidney, that have responded to antimicrobial therapy without the need for a drainage procedure. This report reviews the literature regarding medical treatment ofbacterial abscesses in order to determine the extent of the clinical experience documented to date and to define the clinical, microbiological, and therapeutic features of abscesses responding to medical therapy. Since routine initial therapy for lung and tubo-ovarian abscesses no longer includes a drainage procedure, these cases were excluded. MethodsA MEDLINE search of the literature from 1966 to August 1994 was done to find all English-language reports of bacterial abscesses ...

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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

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Outcome of Medical Treatment of Bacterial Abscesses Without Therapeutic Drainage: Review of Cases Reported in the Literature

Bamberger

1996

Clinical Infectious Diseases

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“…Bacteria often encounter oxygen-limited situations during infection of the host. In many cases, the antibacterial activities of drugs, including fluoroquinolones and aminoglycosides, decrease when oxygen is depleted (1)(2)(3)(4).…”

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confidence: 99%

Elevated Expression of GlpT and UhpT via FNR Activation Contributes to Increased Fosfomycin Susceptibility in Escherichia coli under Anaerobic Conditions

Kurabayashi

Tanimoto

Fueki

et al. 2015

Antimicrob Agents Chemother

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Because a shortage of new antimicrobial agents is a critical issue at present, and with the spread of multidrug-resistant (MDR) pathogens, the use of fosfomycin to treat infections is being revisited as a "last-resort option." This drug offers a particular benefit in that it is more effective against bacteria growing under oxygen-limited conditions, unlike other commonly used antimicrobials, such as fluoroquinolones and aminoglycosides. In this study, we showed that Escherichia coli strains, including enterohemorrhagic E. coli (EHEC), were more susceptible to fosfomycin when grown anaerobically than when grown aerobically, and we investigated how the activity of this drug was enhanced during anaerobic growth of E. coli. Our quantitative PCR analysis and a transport assay showed that E. coli cells grown under anaerobic conditions had higher levels of expression of glpT and uhpT, encoding proteins that transport fosfomycin into cells with their native substrates, i.e., glycerol-3-phosphate and glucose-6-phosphate, and led to increased intracellular accumulation of the drug. Elevation of expression of these genes during anaerobic growth requires FNR, a global transcriptional regulator that is activated under anaerobic conditions. Purified FNR bound to DNA fragments from regions upstream of glpT and uhpT, suggesting that it is an activator of expression of glpT and uhpT during anaerobic growth. We concluded that the increased antibacterial activity of fosfomycin toward E. coli under anaerobic conditions can be attributed to elevated expression of GlpT and UhpT following activation of FNR, leading to increased uptake of the drug.

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“…Acidic pH, reduced 1Department of Medicine, and 2Department of Surgery, University Hospital, R~mistr, 100, Ziirich, Switzerland. oxygen tension or even completely anaerobic conditions have been found in experimental abscesses and in human pus (6)(7)(8). Anaerobes and facultative anaerobes may easily grow or at least survive in a less active physiological state under the pathological conditions described above.…”

mentioning

confidence: 99%

Effect of pathological changes of pH, pO2 and pCO2 on the activity of antimicrobial agents in vitro

König

Simmen

Blaser

1993

Eur. J. Clin. Microbiol. Infect. Dis.

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Since standard susceptibility tests reflect the physiological rather than the pathological conditions prevailing within an infected abdomen, as recently documented, the effect of reduced pH and pO2 and increased pCO2 on the activity of antibiotics in vitro was studied. MICs were determined in vitro under standard culture conditions (MICstandard) and modified conditions (MICmodification) simulating the previously determined pathological values. Various classes of antibiotics were affected differently by the modified conditions. However, within an antibiotic class similar results were obtained for gram-negative and gram-positive pathogens. Median MICmodification/MICstandard ratios were 4 for aminoglycosides, 2 for quinolones and clindamycin, 1 for cephalosporins, and 0.5 for penicillins and vancomycin. Anaerobic conditions and a pH of 6.4 further increased the ratio of aminoglycosides to 8. Ratios were similar within an antibiotic class at inocula of 10(5) or 10(7) cfu/ml. All MICs determined in tests with imipenem against gram-negative and gram-positive bacteria and with vancomycin against gram-positive organisms were below the susceptibility breakpoint, whatever conditions and inocula were employed. In contrast, the percentage of MICs in susceptibility range using high inocula and modified conditions decreased to 78% for penicillins, 73% for cephalosporins, 22% for aminoglycosides, 11% for quinolones and 0% for clindamycin. In conclusion, routine susceptibility testing may overestimate the activity of aminoglycosides and underestimate the activity of beta-lactams under the conditions prevailing during abdominal infection.

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-Lactam Enhancement of Aminoglycoside Activity under Conditions of Reduced pH and Oxygen Tension That May Exist in Infected Tissues

Cited by 40 publications

References 22 publications

Outcome of Medical Treatment of Bacterial Abscesses Without Therapeutic Drainage: Review of Cases Reported in the Literature

Outcome of Medical Treatment of Bacterial Abscesses Without Therapeutic Drainage: Review of Cases Reported in the Literature

Elevated Expression of GlpT and UhpT via FNR Activation Contributes to Increased Fosfomycin Susceptibility in Escherichia coli under Anaerobic Conditions

Effect of pathological changes of pH, pO2 and pCO2 on the activity of antimicrobial agents in vitro

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