Antibiotic Resistance Patterns of Clinical Isolates of
            <i>Serratia marcescens</i>

Rc, Cooksey; Er, Bannister; We, Farrar

doi:10.1128/aac.7.4.396

Cited by 28 publications

(19 citation statements)

References 11 publications

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“…Given the increasing frequency of antibiotic resistance in S. marcescens clinical isolates, especially against "lastresort" carbapenem antibiotics (11,12,53), there is an urgent need to identify novel prophylactic or therapeutic agents that are effective against nosocomial pneumonia. Our model offers a way to reproducibly model human S. marcescens pneumonia in a commonly used inbred mouse strain and is thus suitable for studies to search for lung-specific bacterial pathogenesis factors, new antibiotic/antimicrobials, and host responses during infection and recovery.…”

Section: Discussionmentioning

confidence: 99%

Requirement for Serratia marcescens Cytolysin in a Murine Model of Hemorrhagic Pneumonia

Mares¹,

Medina²,

Cantwell³

et al. 2015

Infect Immun

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Serratia marcescens, a member of the carbapenem-resistant Enterobacteriaceae, is an important emerging pathogen that causes a wide variety of nosocomial infections, spreads rapidly within hospitals, and has a systemic mortality rate of <41%. Despite multiple clinical descriptions of S. marcescens nosocomial pneumonia, little is known regarding the mechanisms of bacterial pathogenesis and the host immune response. To address this gap, we developed an oropharyngeal aspiration model of lethal and sublethal S. marcescens pneumonia in BALB/c mice and extensively characterized the latter. Lethal challenge (>4.0 ؋ 10 6 CFU) was characterized by fulminate hemorrhagic pneumonia with rapid loss of lung function and death. Mice challenged with a sublethal dose (<2.0 ؋ 10 6 CFU) rapidly lost weight, had diminished lung compliance, experienced lung hemorrhage, and responded to the infection with extensive neutrophil infiltration and histopathological changes in tissue architecture. Neutrophil extracellular trap formation and the expression of inflammatory cytokines occurred early after infection. Mice depleted of neutrophils were exquisitely susceptible to an otherwise nonlethal inoculum, thereby demonstrating the requirement for neutrophils in host protection. Mutation of the genes encoding the cytolysin ShlA and its transporter ShlB resulted in attenuated S. marcescens strains that failed to cause profound weight loss, extended illness, hemorrhage, and prolonged lung pathology in mice. This study describes a model of S. marcescens pneumonia that mimics known clinical features of human illness, identifies neutrophils and the toxin ShlA as a key factors important for defense and infection, respectively, and provides a solid foundation for future studies of novel therapeutics for this important opportunistic pathogen. Serratia marcescens is a facultative anaerobic, rod-shaped, Gram-negative bacterium that is ubiquitous in water, in soil, and on plant surfaces. S. marcescens is also an antibiotic-resistant opportunistic pathogen and is among the top 10 causative agents of bloodstream bacterial infections in North America, with a mortality rate of 41% (1-3). In newborns and immunocompromised and intensive care patients, S. marcescens can cause severe infections such as pneumonia (4), bloodstream infections (5), and urinary tract infections, surgical site infections, and ocular infections (6). S. marcescens infections are most often associated with the hospital environment (5), but community-acquired infections are now increasingly diagnosed (7).S. marcescens has acquired notoriety in the last 20 years because of its resistance to multiple antibiotics (7,8). An 8-year surveillance study in Taiwan identified multiple S. marcescens strains that were resistant to the antibiotics ciprofloxacin and levofloxacin (9). Multiple studies have revealed an alarming increase in S. marcescens resistance to carbapenem and other ␤-lactam antibiotics (8, 10, 11). As such, S. marcescens is considered a member of the carbapenem-resistant Enterobac...

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Section: Discussionmentioning

confidence: 99%

Requirement for Serratia marcescens Cytolysin in a Murine Model of Hemorrhagic Pneumonia

Mares¹,

Medina²,

Cantwell³

et al. 2015

Infect Immun

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“…Emergence of gentamicin resistance has been associated with topical (33) and oral (14) therapy. It has been described with gentamicin use in cancer centers (7,14). The hospital of the present study is a general referral and primary care facility and, as such, should be expected to reflect the situation in general hospitals more closely than do these prior studies.…”

Section: Discussionmentioning

confidence: 99%

Gentamicin Use and Pseudomonas and Serratia Resistance: Effect of a Surgical Prophylaxis Regimen

1978

Antimicrob Agents Chemother

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An outbreak of prosthetic valve endocarditis due to methicillin-resistant Staphylococcus epidermidis prompted a change in antimicrobial prophylaxis for open heart surgery in a general hospital from a regimen of aqueous penicillin G, methicillin, and kanamycin to a 5-day regimen of cefazolin and gentamicin. As a result, total gentamicin use in the hospital more than doubled. Increased resistance of pseudomonas and serratia isolates paralleled the increased total use of gentamicin. For pseudomonas species, the incidence of gentamicin resistance increased from 3 to 15%; for serratia species, from 8 to 88%; and for the total of both organisms, from 4 to 28%. Resistance decreased rapidly after removal of gentamicin from the prophylaxis regimen. Review of serratia isolates from the urinary tract showed that gentamicin resistance was associated with prior antibiotic therapy, especially with gentamicin, care on the surgical services, especially the surgical intensive care unit, and presence of indwelling bladder catheters. Gentamicin-use in a 5-day antimicrobial prophylaxis regimen for open heart surgery can represent a large proportion of the total hospital use of that antibiotic, with potential adverse effects on hospital flora.Studies of bacterial endocarditis involving prosthetic heart valves have stressed the considerable morbidity and mortality of this infection (5,11,17,18,20,34,39). Wilson et al. noted a high incidence of gram-negative bacterial infection in both early and, in contrast to other studies, late infections (39). TlPey recommended consideration of a prophylactic regimen consisting of methicillin and gentamicin at the time of prosthetic valve surgery, since this combination would be effective against most bacteria causing early-onset prosthetic valve infection. Further, they suggested that the short duration of the prophylactic regimen would be unlikely to induce resistant bacterial flora and superinfection.We have observed the effects of a similar prophylactic regimen at our hospital. In contrast to the reasonable expectations of Wilson et al., we found substantial changes in bacterial flora. Our data show that prophylactic surgical antibiotic use can represent a large proportion of a hospital's total use of that antibiotic, correlating with induction of resistant bacterial flora. We report this experience to make others aware of such potential adverse effects, with particular reference to open heart surgery antibiotic regimens.

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“…Studies of synergy revealed that moxalactam and cefotaxime, in combination with netilmicin or amikacin, were often synergistic and infrequently antagonistic against cephalothin-and gentamicin-resistant strains. These results suggest that moxalactam and cefotaxime, alone or in combination, may be efficacious in treating infections due to multiply antibiotic-resistant S. marcescens.Over the past decade, Serratia marcescens has achieved preeminence as a cause of serious nosocomial infections (6,21,23,30). Susceptibility to aminoglycoside antibiotics was, at one time, taken for granted, but the emergence of multiply antibiotic-resistant strains has been a cause for concern (23,30).…”

mentioning

confidence: 99%

“…Over the past decade, Serratia marcescens has achieved preeminence as a cause of serious nosocomial infections (6,21,23,30). Susceptibility to aminoglycoside antibiotics was, at one time, taken for granted, but the emergence of multiply antibiotic-resistant strains has been a cause for concern (23,30).…”

mentioning

confidence: 99%

Comparative susceptibilities of clinical isolates of Serratia marcescens to newer cephalosporins, alone and in combination with various aminoglycosides

Markowitz¹,

Sibilla²

1980

Antimicrob Agents Chemother

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We examined 100 clinically significant isolates of Serratia marcescens for susceptibility to newer cephalosporin and cephamycin antibiotics, alone and in combination with various aminoglycosides. Moxalactam and cefotaxime were the most effective agents; all isolates were inhibited by 25 and 50 ,ug/ml, respectively. All strains were susceptible to amikacin at concentrations safely achievable in serum, whereas gentamicin, netilmicin, and tobramycin inhibited 63, 63, and 16% of the isolates, respectively. Moxalactam, cefotaxime, and amikacin were active against gentamicin-susceptible and gentamicin-resistant strains. Studies of synergy revealed that moxalactam and cefotaxime, in combination with netilmicin or amikacin, were often synergistic and infrequently antagonistic against cephalothin-and gentamicin-resistant strains. These results suggest that moxalactam and cefotaxime, alone or in combination, may be efficacious in treating infections due to multiply antibiotic-resistant S. marcescens.Over the past decade, Serratia marcescens has achieved preeminence as a cause of serious nosocomial infections (6,21,23,30). Susceptibility to aminoglycoside antibiotics was, at one time, taken for granted, but the emergence of multiply antibiotic-resistant strains has been a cause for concern (23,30).Cephalosporin antibiotics have been notoriously ineffective against S. marcescens. However, newer generations of cephalosporins, most notably moxalactam (LY127935) and cefotaxime (HR756), have been shown to be extremely active in vitro against both cephalothin-susceptible and cephalothin-resistant strains and some gentamicin-resistant organisms (7,8,10,13,24,27 Only strains judged to be involved in clinically significant infections were studied, including: (i) urinary isolates (36 strains) at more than 100,000 organisms per ml of urine on two consecutive daily urine cultures; (ii) wound isolates (21 strains) when S. marcescens was the only organism cultured from an infected area; (iii) sputum isolates (23 strains) when S. marcescens was consistently isolated in pure culture from a patient with purulent sputum, fever, and pulmonary infiltrates; (iv) blood (17 strains

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Antibiotic Resistance Patterns of Clinical Isolates of Serratia marcescens

Cited by 28 publications

References 11 publications

Requirement for Serratia marcescens Cytolysin in a Murine Model of Hemorrhagic Pneumonia

Requirement for Serratia marcescens Cytolysin in a Murine Model of Hemorrhagic Pneumonia

Gentamicin Use and Pseudomonas and Serratia Resistance: Effect of a Surgical Prophylaxis Regimen

Comparative susceptibilities of clinical isolates of Serratia marcescens to newer cephalosporins, alone and in combination with various aminoglycosides

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