Специализирано списание за хирургия и медицина: Журнал Nedyalkov K., Grozev V., Beshev L.Clostridium septicum associated gas gangrene with fatal outcome in diabetes patient - case report. Journal "MySurgery.bg", April 2014. ISSN: 1314-6785

Nedyalkov K., Grozev V., Beshev L.Clostridium septicum associated gas gangrene with fatal outcome in diabetes patient - case report. Journal "MySurgery.bg", April 2014. ISSN: 1314-6785

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Clostridium septicum associated gas gangrene with fatal outcome in diabetes patient – case report

Nedyalkov K.1; Grozev V.1; Beshev L.2; Nguen D.1; Mirochnik P.1; Edreva V.3; Filipov E.1; Velikov V.2; Tsankov B.2; Iliev S.1;

1 Department of Colo-proctology and Septic Surgery

2 Microbiology and Virology Laboratory

3 Department of Vascular Surgery

University Hospital “ D-r. Georgi Stranski” Plven, Bulgaria

 Gas gangrene (clostridial myonectosis) is a relatively rare surgical infection, usually associated with previous traumatic injuries. In those cases , infection is caused predominantly  by Clostridium perfringens and less often by Clostridium oedematiens, Clostridium septicum, Clostridium histolyticum. Clostridium septicum is main causative agent of spontaneous, non-traumatic gas gangrene, often associated with neoplasma, immune suppression hematological diseases and diabetes. In our case of the infection was observed in diabetes patient who have had intramuscular injection with no data for malignancies. 

 

Clinical case

A 55-years old man with diabetes was admitted in the colo-proctology and septic surgery Clinic of the University hospital “Dr. G. Stranski” in Pleven. The patient reported a prick from a metallic object on the left foot, 3 days earlier. Due to a severe pain and swelling of the left foot surgical incisions were made in another hospital, but the observed gas in the tissues was the reason to immediately refer the patient for treatments in University hospital, with suspected necrotizing gas infection.

On admission (21.30h) the patient was in poor general condition, intoxicated, non-febrile, and conscious. Heart rate was 90 bpm, and blood pressure relatively low 85/60 mm Hg. The local physical examination showed non-vital left foot, multiple incisions, crepitus around the soft tissues over the ankle, and weakened pulse at the left popliteal artery. X-ray of the left foot showed intact bone structure, but multiple poor shadows (gas) in the soft tissues of the foot.

One hour after admission an urgent operation was performed with longitudinal incisions on the lateral, medial and anterior side of the left lower leg. The performed fasciotomia showed expressed swelling of the subfascial soft tissues, vital muscles with normal color and reaction to electrocauterisation. Within the subcutaneous exudate gas bubbles were found, but as the muscles were vital, we estimated that it’s not a case of gas gangrene (Fig.1). A material for microbiology examination was taken, which showed no bacterial growth within 72 hours. After surgery patient therapy included Ceftriaxone 2x1g, Metronidazole 3x500mg, Nadoparin calcium 2x0,6ml, Penthoxyphylline 2x2 amp.

On the next postoperative day, the patient complained of severe pain in the right gluteal region and right hip. Repeated medical history taking, he reported muscle injection manipulation for NSAID performed the previous day at home. Clinical examination established lack of pulsations on right common femoral artery and distally, but preserved ones on the left side. The clinical examination of the right gluteal region showed purple colored skin with tension, inflammatory infiltrate and cracles, reaching distal third of the lower limb. The case was discussed in a team of general and vascular surgeons and estimated as a fulminant gas-productive infection probably due to intramuscular manipulation with possible acute right iliac artery thrombosis. A decision for urgent operation was taken.

The patient was re-admitted at the operating room 45 minutes after the onset of symptoms, with severe hemodynamic instability, RR 70/40mm Hg, severe intoxication and quantitatively disturbed consciousness. Preoperative resuscitation measures were taken and proceeded with surgery. Catheter thrombectomy showed no obstruction either proximally or distally. Incisions starting from right lumbar and sacral regions through the lateral and dorsal part of the right hip and two incisions of the lower leg were made. During fasciotomy, excessive amounts of gas with unpleasant sweet smell were released, but muscles were necrotic, altered and edematous as no purulent exudate was observed. Because of the heavy compartment syndrome there was no bleeding from the muscles and soft tissues. Material for microbiology testing was taken – aspirate and parts of the muscles. The incisions were closed subfascially and richly lavaged with hydrogen peroxide. Drains were inserted in the newly formed cavities for continuous lavage with hydrogen peroxide. The wounds  were tamponed  with hydrogen peroxide soaked compresses.

 

Gas gangrene - clostridium septicum, fatal outcome in diabetes, bacterial gangrene, gas gangrene in diabetes patients, clostridium septicum gas gangrene 

 

 

Fig.1 Status of the left lower limb after surgery. Muscles with reserved vitality.

 Gas gangrene - clostridium septicum, fatal outcome in diabetes, bacterial gangrene, gas gangrene in diabetes patients, clostridium septicum gas gangrene

Fig.2 Position of the patient on the operating table. Due to the severe gas edema of the right gluteal region, the right leg could not lie on the table.

 

Gas gangrene - clostridium septicum, fatal outcome in diabetes, bacterial gangrene, gas gangrene in diabetes patients, clostridium septicum gas gangrene


Fig.3  Position of the patient on the operating room. Mark the difference in the size of both legs.

 Gas gangrene - clostridium septicum, fatal outcome in diabetes, bacterial gangrene, gas gangrene in diabetes patients, clostridium septicum gas gangrene

Fig.4 Right gluteal region. Clearly evident change of skin color and hemorrhagic bullae.

 Gas gangrene - clostridium septicum, fatal outcome in diabetes, bacterial gangrene, gas gangrene in diabetes patients, clostridium septicum gas gangrene

Fig.5 Incisions of the hip and lower leg. Necrotic underlying muscles.

 Gas gangrene - clostridium septicum, fatal outcome in diabetes, bacterial gangrene, gas gangrene in diabetes patients, clostridium septicum gas gangrene

Fig. 6 Through the incisions prolapsed swollen necrotic muscle. Releasing plenty of gas with sweetish odor.

Gas gangrene - clostridium septicum, fatal outcome in diabetes, bacterial gangrene, gas gangrene in diabetes patients, clostridium septicum gas gangrene

Fig.7 Severely edema and necrosis of muscles of the lower leg

Gas gangrene - clostridium septicum, fatal outcome in diabetes, bacterial gangrene, gas gangrene in diabetes patients, clostridium septicum gas gangrene

Fig.8 Incisions of hip and lower leg. Flush drainage of the wounds

Patient was transferred to the ICU in critical medical condition (11:30 a.m.), on mechanical ventilation. The prescribed therapy consisted of Piperacilin/Tazobactam 3x4,5g., Metronidazole 3x500mg. Despite the emergency surgical intervention, reanimation measures and adequate antibacterial therapy, the patient died. The relatives of the patient refused autopsy because religious reasons.

Direct microscopy slides were made from all materials taken during the second surgical intervention, stained by Gram and methylene-blue.  The cultivation was performed on Shedler media, Thioglicolat media, Komkova  and Willson-Blear media and blood agar with 5% sheep blood, Levin media and tripsin-glucose liquid media for anaerobic bacteria. The direct bacterioscopy from all materials showed the presence of large amount of rough, thick Gram-positive rods with parallel cellular walls with cut edges and typical clostridia morphology. In some of the samples from muscle tissue we observed muscle fibers with signs of necrosis and lack of both polymorphonuclear leucocytes and spores. In the aerobic media there was no growth. In the anaerobic media  the results indicated presence of large amount of gas in Komkova-medium and little less gas in Willson-Blear medium on the second hour after inoculation. On the 24th hour there was presence of scandent, web-like growth on the Schedler medium with darkening and strong unpleasant smell. The final identification was performed by automated systems (miniAPI, bio Merieux, France). From all materials we isolated Clostridium septicum with good level of authenticity.

 Gas gangrene - clostridium septicum, fatal outcome in diabetes, bacterial gangrene, gas gangrene in diabetes patients, clostridium septicum gas gangrene

Discussion

Gas gangrene is most commonly observed in large, deep wounds of muscles and other tissues in conditions which attribute to the easy contamination with pathogen clostridial bacteria from the surrounding area – soil, clothes, feces. The microorganisms which cause the infection can be divided into three groups – actively pathogenic (C.perfringens, C.oedematiens, C.septicum), less pathogenic (C.histolyticum, C.sporogenes), and types which are usually not pathogenic, but can be in the presence of other pathogenic bacteria (C.falax, C.bifermentans, C.tertium, C.sordellii) [1]. C.septicum is commonly found in soil, but it is very rarely a causative agent of the infection.

Classic cases of gas gangrene are typical for war-time injuries and are most often caused by C. perfringens. Literature review shows decrease in the incidence of these infections from 5% during First World War to 0,0002% in the Vietnam war. This fact is attributed to improvement in diagnostics as well as progress in the treatment of the infected wounds [2-5]. Contrariwise, the incidence of clostridial infection caused by C. septicum among the civilian population is increasing. Alpern and Dowell found only 11 cases of C. septicum gas gangrene described in the world literature between 1940 and 1967 [6]. Koransky et al presented 27 own cases for the period between 1963 and 1968 and 59 patients for the period between 1969 and 1977, treated in their clinics [7]. According to Katlic et al. the increase in the number of documented cases can be attributed to the development of the diagnostic and identification methods and the techniques for cultivating anaerobic bacteria [8]. ] From the literature review we made we can conclude that the increase of numbers of cases with C. septicum infections can be explained by the increase of patients with impaired immune response [ 9, 10, 11, 12, 13, 14, 15]. Predisposing factors include malignancy of the large bowel, diverticulosis, gastro-intestinal surgery, leukemia and other blood malignancies as well as chemotherapy and radiation therapy and HIV [9, 10, 15, 16]. To these factors we can add the drug-induced immune suppression and badly controlled diabetes [2, 10, 14, 15, 17]. Most of the authors point out the connection between large bowel malignancy and C. septicum infection. This correlation  can be attributed to the vast neoangiogenesis and the disruption of the mucosal layer of the bowel which provides the chance for dissemination of C. septicum in the blood. [2, 11, 13, 16].  This results in multifocal dissemination in most of the cases [2, 8, 10, 11, 12].

Unlike the classic gas gangrene caused by C. perfringens where open wounds are the typical path for infection the cases with C. septicum infection after such wounds are quite rare [2, 10, 16, 17]. In our patient we found two of the pointed risk factors – badly controlled diabetes and improper intramuscular manipulation. The absence of anamnesis and clinical data for malignant process, as well as the multiple areas of involvement and preserved immune response, gave us the base to exclude the possibility for malignant process. On the other hand, we exclude the possible origin of the infection from the puncture wound on the left foot as there was neither clinical, nor microbiological data for clostridial infection there. This leaves the puncture wound from the intramuscular injection as the most probable portal of entry for the infection. Another aggravating factor for the development of the pathological process is the application of drug which can cause damage to the surrounding tissues.[1]In our literature review, we found only few cases with post-injection C.septicum gas gangrene. [17,18].

The clinical aspect of the fulminant C.septicum infection is presented with symptoms developing within the 5-72 hour [2,11,14,15,20]. After an incubation period from several hours to three days, the infection begins rapidly usually with crescendo-type pain, which is intolerable for the patient [15], no matter the poor physical findings. Patients quickly develop severe intoxication syndrome with disturbance in the consciousness, even delirium [15]. The diagnosis becomes obvious in a few hours when crepitation involves tissues. Together with the changes in the deep tissues the overlying skin also gains typical changes, appearing shiny with a lot of stretch marks due to the rapid increase of produced gas. Shortly after that, the skin color changes into lividly-black [15]. The increased pressure in the soft tissues leads to severe compartment syndrome which pressurizes the main arterial vessels, as we observed in our patient. There was lack of arterial pulsations without thrombosis. We support Rai et al. statement, that the lack of distal pulse is very typical sign for C.septicum associated gas gangrene[10].  What’s more, this can lead to difficulties in the differential diagnosis.

In many cases described in literature, authors put accent on the quickly forming hemorrhagic bullas, filled with hemolized blood [2, 9, 10, 11, 12, 21]. That can be attributed to the rapidly proliferating bacteria in the involved tissues and the production of huge amount of exotoxin with direct toxic effect on the polymorphonuclear leucocytes, red blood cells, cardiac muscle cells and the tubular epithelium of the kidneys [22,23,24]. This explains the haemorrhagic type of exudate in the bullas, as well as the lack of polymorphonuclear leucocytes in the direct bacterioscopy [9].Reviewing literature it makes sense is the rich finding on physical examination and the poor one in the laboratory test and also the lack of increased body temperature [2,14,15].

The medical state in these patients worsens with the development of septic shock and multy-organ failure with collapse of all vital signs. This can be explained with the serious cardiac depression, severe metabolic acidosis caused by microcirculation failure associated with the increased tissue pressure in the involved tissues and the hemolytic anemia. That way evolving of irreversible shock compromises the set of resuscitation measures. Literature data suggest that mortality varies from 67% to 100% in C.septicum gas gangrene [15], and patients dying within the first 24 hours after diagnosis [2,8,11,12]. According to Gibson the average mortality rate of the clostridial infections is around 25%, whereas the same value in C.septicum infections is above 80% in aggressively treated patients and 100% in untreated cases [26]. This is why the early and aggressive surgical treatment combined with adequate antibacterial therapy can be lifesaving [9, 15].

Treatment of clostridial myonecrosis must be immediate and including both aggressive surgical intervention and adequate antibacterial therapy. The surgical treatment is essential for the outcome [2,10], and its volume depends on the anatomical localization and varies from incision to amputation [8,10,11]. It is mandatory to reach the deep tissues and to achieve hyperoxygenetion, which can be done by hydrogen peroxide lavage. There is variety of schemes for antibacterial admission in cases with gas gangrene. Different authors give advantage to Penicillin, Clindamycin, Piperacillin/Tazobactam, Metronidazole, new Fluroquinolones, Cefazolin, Chloramphenicol, Vancomycin [2,8,11,15]. Despite the results are often unsatisfactory, in the last years Clindamycin is established to be more effective then Penicillin because its ability to block the exocytosis of toxin from the bacterial cells in animal models [27]. The unsatisfactory result of antibiotic admission can be explained by damaged micro- and macrocirculation, resulting in inability to reach the therapeutic concentrations of the drug in the infected areas.

Well recognized is the role of hyperbaric oxygenation in the treatment of gas gangrene [28]. In large studies conducted by Rudge, in 1278 cases with gas gangrene where he combined antibacterial, surgery and hyperbaric oxygenation treatment, the survival rates reach 80% [29]. Hart and Osterhout report that hyperbaric oxygenation lowers mortality rates from 70% to 25% [30].  Cases with C.septicum gas gangrene are less susceptible to this method of treatment because of its extended aero-tolerance compared to other clostridial bacteria [31]. Additional element of the treatment can be application of anti-gas gangrene serum in therapeutic doses and anti-gas gangrene bacteriophage [28].

Conclusion

The rapidly developing infection can be managed only in the early stages of its evolution where there is still a little amount of gas in the tissues. In later stages, equalization between the tissue pressure and the arterial pressure leads to lack of pulse, which on our opinion is an end stage of the disease which is incurable unfortunately. Specific localizations such as gluteal muscles, anterior and lateral abdominal wall and etc. exclude the possibility for effective treatment and determine the lethal exit for the patient.

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